Nuclear factor gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][4][5] NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.[6][7][8][9][10][11]

Hepatic nuclear factors

Hepatic nuclear factors (HNFs) bind through their DNA-binding domain (DBD) to consensus elements (A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T), resulting in gene transcription.[12]

Nuclear factor 1

Nuclear factor 1 (NF-1) is a family of closely related transcription factors that constitutively bind as dimers to specific sequences of DNA with high affinity.[13] Family members contain an unusual DNA binding domain that binds to the recognition sequence 5'-TTGGCXXXXXGCCAA-3'.[14]

Nuclear factor-B/Rel transcription factors

"The NF‐κB/Rel family of eukaryotic transcription factors controls many mammalian genes of significant biomedical importance, including genes encoding pro‐inflammatory cytokines, interferones, major histocompatibility complex (MHC) proteins, growth factors, cell adhesion molecules, but also viruses such as the human immunodeficiency virus (HIV) or Herpes (Baeuerle and Henkel, 1994; Thanos and Maniatis, 1995; Baeuerle and Baltimore, 1996; Baldwin, 1996; Chytil and Verdine, 1996)."[15]

"The transcription factor NF-κB (nuclear factor κB) is a central mediator of inflammatory and apoptotic signaling in the cell. The protein kinase RIP-2 is a member of the CARD protein family (caspase activation and recruitment domain, also known as CARD3, Ripk2, CARDIAK, RICK, and CCK), and has been shown to be an activator of NF-κB. [The] inflammatory cytokines TNF-α, IL-1β, and IFN-γ induced RIP-2 transcription and translation in endothelial cells. [Multiple] NF-κB response elements were found in the upstream regions of the human and mouse RIP-2 genes. [...] RIP-2 has been shown to positively modulate NF-κB by binding IKKγ (IκB kinase γ), a component of the IKK complex. [...] RIP-2 is the first reported NF-κB-dependent protein kinase that positively regulates NF-κB activity."[16]

Nuclear factor of activated T cells

DNA binding sites

The "natural 11 bp 𝜿B binding site MHC H-2 [is 3'-CCCCTAAGGGG-5'] which is well ordered in our structure."[15]

CAAT box gene transcriptions

CAAT boxes: CCAAT-box-binding transcription factor, TGGCA-binding protein are used by some nuclear factors.[17]

CAAT box nuclear factor genes

Gene ID: 4774 is NFIA nuclear factor I A aka CCAAT-box-binding transcription factor, TGGCA-binding protein, on 1p31.3: "This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. "[17]

  1. NP_001128145.1 nuclear factor 1 A-type isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1."[17]
  2. NP_001138983.1 nuclear factor 1 A-type isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding region compared to variant 1. The resulting protein (isoform 3) has a shorter and distinct N-terminus compared to isoform 1."[17]
  3. NP_001138984.1 nuclear factor 1 A-type isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR and coding region compared to variant 1. The resulting protein (isoform 4) has a longer and distinct N-terminus compared to isoform 1."[17]
  4. NP_005586.1 nuclear factor 1 A-type isoform 2: "Transcript Variant: This variant (2) lacks an alternate segment in the 3' UTR, which shifts the reading frame, compared to variant 1. The resulting protein (isoform 2) has a shorter and distinct C-terminus when it is compared to isoform 1."[17]

Gene ID: 4781 is NFIB nuclear factor I B aka CCAAT-box-binding transcription factor or TGGCA-binding protein on 9p23-p22.3.[18]

  1. NP_001177666.1 nuclear factor 1 B-type isoform 1: "Transcript Variant: This variant (1) encodes isoform 1."[18]
  2. NP_001177667.1 nuclear factor 1 B-type isoform 2: "Transcript Variant: This variant (2) has multiple differences, one of which results in translation from an upstream start codon, compared to variant 1. The resulting protein (isoform 2) has a different and longer N-terminus and a shorter C-terminus when it is compared to isoform 1."[18]
  3. NP_001269716.1 nuclear factor 1 B-type isoform 4: "Transcript Variant: This variant (4) contains a distinct 5' UTR, lacks an in-frame portion of the 5' coding region and contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (4) is shorter compared to isoform 1."[18]
  4. NP_001356387.1 nuclear factor 1 B-type isoform 5: "Transcript Variant: This variant (5) encodes the longest isoform (5)."[18]
  5. NP_001356388.1 nuclear factor 1 B-type isoform 6 [variant 6].[18]
  6. NP_001356389.1 nuclear factor 1 B-type isoform 7 [variant 7].[18]
  7. NP_001356390.1 nuclear factor 1 B-type isoform 8 [variant 8].[18]
  8. NP_001356391.1 nuclear factor 1 B-type isoform 9 [variant 9].[18]
  9. NP_001356392.1 nuclear factor 1 B-type isoform 10 [variant 10].[18]
  10. NP_001356393.1 nuclear factor 1 B-type isoform 11 [variant 11].[18]
  11. NP_001356394.1 nuclear factor 1 B-type isoform 12 [variant 12].[18]
  12. NP_001356395.1 nuclear factor 1 B-type isoform 13 [variant 13].[18]
  13. NP_001356396.1 nuclear factor 1 B-type isoform 14 [variant 14].[18]
  14. NP_001356397.1 nuclear factor 1 B-type isoform 15 [variant 15].[18]
  15. NP_001356398.1 nuclear factor 1 B-type isoform 16 [variant 16].[18]
  16. NP_001356399.1 nuclear factor 1 B-type isoform 17 [variant 17].[18]
  17. NP_001356400.1 nuclear factor 1 B-type isoform 18 [variant 18].[18]
  18. NP_001356401.1 nuclear factor 1 B-type isoform 19 [variant 19].[18]
  19. NP_001356402.1 nuclear factor 1 B-type isoform 20 [variant 20].[18]
  20. NP_001356403.1 nuclear factor 1 B-type isoform 21 [variant 21].[18]
  21. NP_001356404.1 nuclear factor 1 B-type isoform 22 [variant 22].[18]
  22. NP_001356405.1 nuclear factor 1 B-type isoform 23 [variant 23].[18]
  23. NP_001356406.1 nuclear factor 1 B-type isoform 24 [variant 24].[18]
  24. NP_001356407.1 nuclear factor 1 B-type isoform 25 [variant 25].[18]
  25. NP_001356408.1 nuclear factor 1 B-type isoform 26 [variant 26].[18]
  26. NP_001356409.1 nuclear factor 1 B-type isoform 27 [variant 27].[18]
  27. NP_001356410.1 nuclear factor 1 B-type isoform 28 [variant 28].[18]
  28. NP_005587.2 nuclear factor 1 B-type isoform 3: "Transcript Variant: This variant (3) lacks alternate exons in the 3' end, compared to variant 1. The resulting protein (isoform 3) is shorter when it is compared to isoform 1."[18]

Gene ID: 4782 is NFIC nuclear factor I C aka CCAAT-box-binding transcription factor, TGGCA-binding protein on 19p13.3: "The protein encoded by this gene belongs to the CTF/NF-I family. These are dimeric DNA-binding proteins, and function as cellular transcription factors and as replication factors for adenovirus DNA replication. Alternatively spliced transcript variants encoding different isoforms have been described for this gene."[19]

  1. NP_001231931.1 nuclear factor 1 C-type isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."[19]
  2. NP_001231933.1 nuclear factor 1 C-type isoform 3: "Transcript Variant: This variant (3) lacks an exon in the 3' coding region compared to variant 1. This results in a frame-shift, and a shorter isoform (3) with a distinct C-terminus compared to isoform 1."[19]
  3. NP_001231934.1 nuclear factor 1 C-type isoform 4: "Transcript Variant: This variant (4) contains an alternate 5' terminal exon, and lacks an exon in the 3' coding region (causing a frame-shift) compared to variant 1. This results in translation initiation from an alternate start codon, and a shorter isoform (4) with distinct N- and C- termini compared to isoform 1."[19]
  4. NP_005588.2 nuclear factor 1 C-type isoform 5: "Transcript Variant: This variant (5) lacks two consecutive in-frame coding exons compared to variant 1. This results in a shorter isoform (5) missing an internal protein segment compared to isoform 1."[19]
  5. NP_995315.1 nuclear factor 1 C-type isoform 2: "Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an alternate start codon, and a shorter isoform (2) with a distinct N-terminus compared to isoform 1."[19]

Gene ID: 4784 is NFIX nuclear factor I X aka CCAAT-box-binding transcription factor, TGGCA-binding protein, on 19p13.13: "The protein encoded by this gene is a transcription factor that binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3 in viral and cellular promoters. The encoded protein can also stimulate adenovirus replication in vitro. Three transcript variants encoding different isoforms have been found for this gene."[20]

  1. NP_001257972.1 nuclear factor 1 X-type isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."[20]
  2. NP_001257973.1 nuclear factor 1 X-type isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and lacks an alternate 3' exon compared to variant 1, that causes a frameshift. The resulting isoform (3) has shorter and distinct N- and C-termini compared to isoform 1."[20]
  3. NP_001352831.1 nuclear factor 1 X-type isoform 4 [variant 4].[20]
  4. NP_001352911.1 nuclear factor 1 X-type isoform 5 [variant 5].[20]
  5. NP_001352912.1 nuclear factor 1 X-type isoform 6 [variant 6].[20]
  6. NP_001352913.1 nuclear factor 1 X-type isoform 7 [variant 7].[20]
  7. NP_001352914.1 nuclear factor 1 X-type isoform 8 [variant 8].[20]
  8. NP_001365333.1 nuclear factor 1 X-type isoform 9 [variant 9].[20]
  9. NP_001365334.1 nuclear factor 1 X-type isoform 10 [variant 10].[20]
  10. NP_002492.2 nuclear factor 1 X-type isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and lacks an alternate 3' exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has shorter and distinct N- and C-termini compared to isoform 1."[20]

Gene ID: 4800 is NFYA nuclear transcription factor Y subunit alpha aka CAAT-box DNA binding protein subunit A, CCAAT-binding transcription factor subunit B on 6p21.1: "The protein encoded by this gene is one subunit of a trimeric complex, forming a highly conserved transcription factor that binds to CCAAT motifs in the promoter regions in a variety of genes. Subunit A associates with a tight dimer composed of the B and C subunits, resulting in a trimer that binds to DNA with high specificity and affinity. The sequence specific interactions of the complex are made by the A subunit, suggesting a role as the regulatory subunit. In addition, there is evidence of post-transcriptional regulation in this gene product, either by protein degradation or control of translation. Further regulation is represented by alternative splicing in the glutamine-rich activation domain, with clear tissue-specific preferences for the two isoforms."[21]

  1. NP_002496.1 nuclear transcription factor Y subunit alpha isoform 1: "Transcript Variant: This variant (1) includes alternate exon B, resulting in the long isoform, isoform 1."[21]
  2. NP_068351.1 nuclear transcription factor Y subunit alpha isoform 2: "Transcript Variant: This variant (2) is missing alternate exon B, resulting in the short isoform, isoform 2."[21]

Gene ID: 4801 is NFYB nuclear transcription factor Y subunit beta aka CCAAT-binding transcription factor subunit A on 12q23.3: "The protein encoded by this gene is one subunit of a trimeric complex, forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoter regions in a variety of genes. This gene product, subunit B, forms a tight dimer with the C subunit, a prerequisite for subunit A association. The resulting trimer binds to DNA with high specificity and affinity. Subunits B and C each contain a histone-like motif. Observation of the histone nature of these subunits is supported by two types of evidence; protein sequence alignments and experiments with mutants."[22]

Gene ID: 4802 is NFYC nuclear transcription factor Y subunit gamma aka CCAAT binding factor subunit C on 1p34.2: "This gene encodes one subunit of a trimeric complex forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoters of a variety of genes. The encoded protein, subunit C, forms a tight dimer with the B subunit, a prerequisite for subunit A association. The resulting trimer binds to DNA with high specificity and affinity. Subunits B and C each contain a histone-like motif. Multiple transcript variants encoding different isoforms have been found for this gene."[23]

  1. NP_001136059.1 nuclear transcription factor Y subunit gamma isoform 3: "Transcript Variant: This variant (3) lacks an alternate in-frame exon and uses an alternate splice site in the 3' coding region, compared to variant 1. The resulting isoform (3) has the same N- and C- termini but lacks an internal segment and one residue near the C-terminus, compared to isoform 1."[23]
  2. NP_001136060.1 nuclear transcription factor Y subunit gamma isoform 1: "Transcript Variant: This variant (1) encodes isoform 1."[23]
  3. NP_001136061.1 nuclear transcription factor Y subunit gamma isoform 4: "Transcript Variant: This variant (4) lacks two alternate in-frame exons in the 5' and 3' coding regions, compared to variant 1. The resulting isoform (4) has the same N- and C- termini but lacks two internal segments, compared to isoform 1."[23]
  4. NP_001136062.1 nuclear transcription factor Y subunit gamma isoform 5: "Transcript Variant: This variant (5) has an alternate splice pattern in the 5' UTR, lacks an alternate exon in the 3' coding region, and uses an alternate splice site in the central coding region, compared to variant 1. the resulting isoform (5) has the same N- and C- termini but lacks two internal segments, compared to isoform 1."[23]
  5. NP_001295043.1 nuclear transcription factor Y subunit gamma isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR and uses an alternate in-frame splice acceptor site in the 3' terminal exon compared to variant 1. The resulting isoform (6) has the same N- and C- termini but contains an additional segment in the 3' coding region, compared to isoform 1."[23]
  6. NP_001295044.1 nuclear transcription factor Y subunit gamma isoform 7: "Transcript Variant: This variant (7) differs in the 5' UTR, lacks an alternate in-frame exon in the central coding region, and uses an alternate in-frame splice acceptor site in the 3' terminal exon compared to variant 1. The resulting isoform (7) has the same N- and C- termini but lacks a segment in the central coding region, and contains an additional segment in the 3' coding region, compared to isoform 1."[23]
  7. NP_055038.2 nuclear transcription factor Y subunit gamma isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (2) has the same N- and C- termini but lacks an internal segment, compared to isoform 1."[23]

Leucine zippers

Leucine zippers are a dimerization motif of the BZIP domain (bZIP) (Basic-region leucine zipper) class of eukaryotic transcription factors.[24] The bZIP domain is 60 to 80 amino acids in length with a highly conserved DNA binding basic region and a more diversified leucine zipper dimerization region.[25] The localization of the leucines are critical for the DNA binding to the proteins. Leucine zippers are present in both eukaryotic and prokaryotic regulatory proteins, but are mainly a feature of eukaryotes.

They can also be annotated simply as ZIPs, and ZIP-like motifs have been found in proteins other than transcription factors and are thought to be one of the general protein modules for protein–protein interactions.[26]

The bZIP interacts with DNA via basic, amine residues (see basic amino acids in (provided table (sort by pH)) of certain amino acids in the "basic" domain, such as lysines and arginines. These basic residues interact in the major groove of the DNA, forming sequence-specific interactions. The mechanism of transcriptional regulation by bZIP proteins has been studied in detail.

"Most bZIP proteins show high binding affinity for the ACGT motifs, which include CACGTG (G box), GACGTC (C box), TACGTA (A box), AACGTT (T box), and a GCN4 motif, namely TGA(G/C)TCA (Landschulz1988;[27] Nijhawan2008[28])."[25]

The bZIP heterodimers exist in a variety of eukaryotes and are more common in organisms with higher evolution complexity.[29] Heterodimeric bZIP proteins differ from homodimeric bZIP and from each other in protein-protein interaction affinity.[30] These heterodimers exhibit complex DNA binding specificity. When combined with a different partner, most of the bZIP pairs bind to DNA sequences that each individual partner prefers. In some cases, dimerization of different bZIP partners can change the DNA sequence that the pair targets in a manner that could not have been predicted based on the preferences of each partner alone. This suggests that, as heterodimers, bZIP transcription factors are able to change their preferences for which location they target in the DNA. The ability of bZIP domain forming dimers with different partners greatly expands the locations on the genome to which bZIP transcription factors can bind and from which they can regulate gene expression.[30]

A small number of bZIP factors such as OsOBF1 can also recognize palindromic sequences.[31] However, the others, including LIP19, OsZIP-2a, and OsZIP-2b, do not bind to DNA sequences. Instead, these bZIP proteins form heterodimers with other bZIPs to regulate transcriptional activities.[31][32]

Leucine zipper nuclear factor genes

Gene ID: 571 is BACH1 BTB domain and CNC homolog 1 on 21q21.3: "This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene."[33]

  1. NP_001177.1 transcription regulator protein BACH1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein."[33]
  2. NP_996749.1 transcription regulator protein BACH1: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 encode the same protein."[33]

Gene ID: 3954 is LETM1 leucine zipper and EF-hand containing transmembrane protein 1 on 4p16.3: "This gene encodes a protein that is localized to the inner mitochondrial membrane. The protein functions to maintain the mitochondrial tubular shapes and is required for normal mitochondrial morphology and cellular viability. Mutations in this gene cause Wolf-Hirschhorn syndrome, a complex malformation syndrome caused by the deletion of parts of the distal short arm of chromosome 4. Related pseudogenes have been identified on chromosomes 8, 15 and 19."[34]

  1. NP_036450.1 mitochondrial proton/calcium exchanger protein precursor.[34]

Gene ID: 4778 is NFE2 nuclear factor, erythroid 2, aka leucine zipper protein NF-E2, p45 NF-E2, on 12q13.13.[35]

  1. NP_001129495.1 transcription factor NF-E2 45 kDa subunit: "Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein."[35]
  2. NP_001248390.1 transcription factor NF-E2 45 kDa subunit: "Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein."[35]
  3. NP_006154.1 transcription factor NF-E2 45 kDa subunit: "Transcript Variant: This variant (1) represents the shortest transcript. Variants 1, 2 and 3 encode the same protein."[35]

Gene ID: 4779 is NFE2L1 nuclear factor, erythroid 2 like 1 aka transcription factor 11 (basic leucine zipper type) on 17q21.32: "This gene encodes a protein that is involved in globin gene expression in erythrocytes. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene, NFE2L1, and for "nuclear respiratory factor 1" which has an official symbol of NRF1."[36]

  1. NP_001317190.1 endoplasmic reticulum membrane sensor NFE2L1 isoform 2 [variant 2].[36]
  2. NP_001317191.1 endoplasmic reticulum membrane sensor NFE2L1 isoform 3 [variant 3].[36]
  3. NP_003195.1 endoplasmic reticulum membrane sensor NFE2L1 isoform 1 [variant 1].[36]

Gene ID: 4780 is NFE2L2 nuclear factor, erythroid 2 like 2 on 2q31.2: "This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene."[37]

  1. NP_001138884.1 nuclear factor erythroid 2-related factor 2 isoform 2: "Transcript Variant: This variant (2) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein."[37]
  2. NP_001138885.1 nuclear factor erythroid 2-related factor 2 isoform 3: "Transcript Variant: This variant (3) represents use of an alternate promoter and 5' UTR, uses a downstream start codon, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (3) has a shorter N-terminus and is missing an internal segment, compared to isoform 1."[37]
  3. NP_001300829.1 nuclear factor erythroid 2-related factor 2 isoform 2: "Transcript Variant: This variant (4) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein."[37]
  4. NP_001300830.1 nuclear factor erythroid 2-related factor 2 isoform 2: "Transcript Variant: This variant (5) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein."[37]
  5. NP_001300831.1 nuclear factor erythroid 2-related factor 2 isoform 4: "Transcript Variant: This variant (6) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The resulting isoform (4) is shorter compared to isoform 1."[37]
  6. NP_001300832.1 nuclear factor erythroid 2-related factor 2 isoform 5: "Transcript Variant: This variant (7) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting isoform (5) is shorter compared to isoform 1."[37]
  7. NP_001300833.1 nuclear factor erythroid 2-related factor 2 isoform 6: "Transcript Variant: This variant (8) represents use of an alternate promoter and 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (6) is shorter compared to isoform 1."[37]
  8. NP_006155.2 nuclear factor erythroid 2-related factor 2 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[37]

Gene ID: 4783 is NFIL3 nuclear factor, interleukin 3 regulated on 9q22.31: "The protein encoded by this gene is a transcriptional regulator that binds as a homodimer to activating transcription factor (ATF) sites in many cellular and viral promoters. The encoded protein represses PER1 and PER2 expression and therefore plays a role in the regulation of circadian rhythm. Three transcript variants encoding the same protein have been found for this gene."[38]

  1. NP_001276928.1 nuclear factor interleukin-3-regulated protein: "Transcript Variant: This variant (1) represents the longest transcript. All three variants encode the same protein."[38] "NFIL3, also called E4 promoter-binding protein 4 (E4BP4), is a Basic leucine zipper (bZIP) transcription factor that was independently identified as a transactivator of the IL3 promoter in T-cells and as a transcriptional repressor that binds to a DNA sequence site in the adenovirus E4 promoter. Its expression levels are regulated by cytokines and it plays crucial functions in the immune system. It is required for the development of natural killer cells and CD8+ conventional dendritic cells. In B-cells, NFIL3 mediates immunoglobulin heavy chain class switching that is required for IgE production, thereby influencing allergic and pathogenic immune responses. It is also involved in the polarization of T helper responses. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription."[39]
  2. NP_001276929.1 nuclear factor interleukin-3-regulated protein: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All three variants encode the same protein."[38]
  3. NP_005375.2 nuclear factor interleukin-3-regulated protein: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All three variants encode the same protein."[38]

Gene ID: 4901 is NRL neural retina leucine zipper on 14q11.2-q12: "This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases."[40]

  1. NP_001341697.1 neural retina-specific leucine zipper protein isoform 1 [variant 2].[40]
  2. NP_001341698.1 neural retina-specific leucine zipper protein isoform 1 [variant 3].[40]
  3. NP_001341699.1 neural retina-specific leucine zipper protein isoform 2 [variant 4].[40]
  4. NP_006168.1 neural retina-specific leucine zipper protein isoform 1 [variant 1].[40]

Gene ID: 5971 is RELB RELB proto-oncogene, NF-kB subunit on 19q13.32.[41] "This domain is a leucine zipper found in RelB transcription factors."[42]

Gene ID: 7798 is LUZP1 leucine zipper protein 1 on 1p36.12: "This gene encodes a protein that contains a leucine zipper motif. The exact function of the encoded protein is not known. In mice this gene affects neural tube closure. Alternative splicing results in multiple transcript variants."[43]

  1. NP_001136018.1 leucine zipper protein 1: "Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein."[43]
  2. NP_361013.3 leucine zipper protein 1: "Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein."[43]

Gene ID: 8216 is LZTR1 leucine zipper like transcription regulator 1 on 22q11.21; 22q11.1-q11.2: "This gene encodes a member of the BTB-kelch superfamily. Initially described as a putative transcriptional regulator based on weak homology to members of the basic leucine zipper-like family, the encoded protein subsequently has been shown to localize exclusively to the Golgi network where it may help stabilize the Gogli complex. Deletion of this gene may be associated with DiGeorge syndrome."[44]

Gene ID: 8548 is BLZF1 basic leucine zipper nuclear factor 1 on 1q24.2.[45]

  1. NP_001307901.1 golgin-45 isoform 2 [variant 2].[45]
  2. NP_001307902.1 golgin-45 isoform 1 [variant 3].[45]
  3. NP_003657.1 golgin-45 isoform 1 [variant 1].[45]

Gene ID: 9689 is BZW1 basic leucine zipper and W2 domains 1 on 2q33.1.[46]

  1. NP_001193996.1 basic leucine zipper and W2 domain-containing protein 1 isoform 1: "Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform 1."[46]
  2. NP_001193997.1 basic leucine zipper and W2 domain-containing protein 1 isoform 2: "Transcript Variant: This variant (2) includes an alternate 5' terminal exon, compared to variant 1. It encodes isoform 2, which is longer and has a distinct N-terminus, compared to isoform 1."[46]
  3. NP_001193998.1 basic leucine zipper and W2 domain-containing protein 1 isoform 3: "Transcript Variant: This variant (3) uses an alternate 5' terminal exon, compared to variant 1. It encodes isoform 3, which is longer and has a distinct N-terminus, compared to isoform 1."[46]
  4. NP_001308617.1 basic leucine zipper and W2 domain-containing protein 1 isoform 1 [variant 5].[46]
  5. NP_001308619.1 basic leucine zipper and W2 domain-containing protein 1 isoform 1 [variant 6].[46]
  6. NP_001308620.1 basic leucine zipper and W2 domain-containing protein 1 isoform 5 [variant 7].[46]
  7. NP_001308622.1 basic leucine zipper and W2 domain-containing protein 1 isoform 6 [variant 8].[46]
  8. NP_001308623.1 basic leucine zipper and W2 domain-containing protein 1 isoform 7 [variant 9].[46]
  9. NP_055485.2 basic leucine zipper and W2 domain-containing protein 1 isoform 4: "Transcript Variant: This variant (4) uses an alternate in-frame splice site in the coding region, compared to variant 1. It encodes isoform 4, which is shorter than isoform 1."[46]

Gene ID: 9833 is MELK maternal embryonic leucine zipper kinase on 9p13.2.[47]

  1. NP_001243614.1 maternal embryonic leucine zipper kinase isoform 2: "Transcript Variant: This variant (2) lacks an exon in the 3' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1."[47]
  2. NP_001243616.1 maternal embryonic leucine zipper kinase isoform 3: "Transcript Variant: This variant (3) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1."[47]
  3. NP_001243617.1 maternal embryonic leucine zipper kinase isoform 4: "Transcript Variant: This variant (4) lacks two consecutive exons in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."[47]
  4. NP_001243618.1 maternal embryonic leucine zipper kinase isoform 5: "Transcript Variant: This variant (5) initiates translation at an alternate start codon and lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (5) is shorter and has a distinct N-terminus, compared to isoform 1."[47]
  5. NP_001243619.1 maternal embryonic leucine zipper kinase isoform 6: "Transcript Variant: This variant (6) initiates translation at an alternate start codon and lacks two consecutive exons in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (6) is shorter and has a distinct N-terminus, compared to isoform 1."[47]
  6. NP_001243620.1 maternal embryonic leucine zipper kinase isoform 7: "Transcript Variant: This variant (7) initiates translation at an alternate start codon and lacks two exons in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (7) is shorter and has a distinct N-terminus, compared to isoform 1."[47]
  7. NP_001243621.1 maternal embryonic leucine zipper kinase isoform 8: "Transcript Variant: This variant (8) lacks three exons in the 5' coding region and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (8) has a shorter N-terminus, compared to isoform 1."[47]
  8. NP_001243622.1 maternal embryonic leucine zipper kinase isoform 9: "Transcript Variant: This variant (9) lacks two consecutive exons in the 5' region and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (9) has a shorter N-terminus, compared to isoform 1."[47]
  9. NP_055606.1 maternal embryonic leucine zipper kinase isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."[47]

Gene ID: 10538 is BATF basic leucine zipper ATF-like transcription factor on 14q24.3: "The protein encoded by this gene is a nuclear basic leucine zipper protein that belongs to the AP-1/ATF superfamily of transcription factors. The leucine zipper of this protein mediates dimerization with members of the Jun family of proteins. This protein is thought to be a negative regulator of AP-1/ATF transcriptional events."[48] "Basic leucine zipper (bZIP) transcription factor ATF-like (BATF or SFA2), BATF2 (or SARI) and BATF3 form heterodimers with Jun proteins. They function as inhibitors of AP-1-driven transcription. Unlike most bZIP transcription factors that contain additional domains, BATF and BATF3 contain only the the bZIP DNA-binding and dimerization domain. BATF2 contains an additional C-terminal domain of unknown function. BATF:Jun hetrodimers preferentially bind to TPA response elements (TREs) with the consensus sequence TGA(C/G)TCA, and can also bind to a TGACGTCA cyclic AMP response element (CRE). In addition to negative regulation, BATF proteins also show positive transcriptional activities in the development of classical dendritic cells and T helper cell subsets, and in antibody production. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription."[49]

Gene ID: 11178 is LZTS1 leucine zipper tumor suppressor 1 on 8p21.3: "This gene encodes a tumor suppressor protein that is ubiquitously expressed in normal tissues. In uveal melanomas, expression of this protein is silenced in rapidly metastasizing and metastatic tumor cells but has normal expression in slowly metastasizing or nonmetastasizing tumor cells. This protein may have a role in cell-cycle control by interacting with the Cdk1/cyclinB1 complex. This gene is located on chromosomal region 8p22. Loss of heterozygosity (LOH) in the 8p arm is a common characteristic of many types of cancer."[50]

  1. NP_001349813.1 leucine zipper putative tumor suppressor 1 [variant 2].[50]
  2. NP_066300.1 leucine zipper putative tumor suppressor 1 [variant 1].[50]

Gene ID: 23641 is LDOC1 LDOC1 regulator of NFKB signaling on Xq27.1: "The protein encoded by this gene contains a leucine zipper-like motif and a proline-rich region that shares marked similarity with an SH3-binding domain. The protein localizes to the nucleus and is down-regulated in some cancer cell lines. It is thought to regulate the transcriptional response mediated by the nuclear factor kappa B (NF-kappaB). The gene has been proposed as a tumor suppressor gene whose protein product may have an important role in the development and/or progression of some cancers."[51]

Gene ID: 26060 is APPL1 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 on 3p14.3: "The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus."[52]

Gene ID: 28969 is BZW2 basic leucine zipper and W2 domains 2 on 7p21.1.[53]

  1. NP_001153239.1 basic leucine zipper and W2 domain-containing protein 2 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 4 encode the same isoform (1)."[53]
  2. NP_001349646.1 basic leucine zipper and W2 domain-containing protein 2 isoform 1: "Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1)."[53]
  3. NP_001349647.1 basic leucine zipper and W2 domain-containing protein 2 isoform 2: "Transcript Variant: This variant (3) lacks an exon in the 5' coding region compared to variant 1, resulting in the use of a downstream start codon. The encoded isoform (2) has a shorter N-terminus compared to isoform 1. Variants 3 and 5 encode the same isoform (2)."[53]
  4. NP_001349648.1 basic leucine zipper and W2 domain-containing protein 2 isoform 2: "Transcript Variant: This variant (5) differs in the 5' UTR and lacks an exon in the 5' coding region compared to variant 1, resulting in the use of a downstream start codon. The encoded isoform (2) has a shorter N-terminus compared to isoform 1. Variants 3 and 5 encode the same isoform (2)."[53]
  5. NP_054757.1 basic leucine zipper and W2 domain-containing protein 2 isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1)."[53]

Gene ID: 51213 is LUZP4 leucine zipper protein 4 on Xq23: "This gene encodes a leucine-zipper protein that was first defined as a cancer testis antigens. The encoded protein is an RNA binding protein that interacts with the mRNA export receptor nuclear RNA export factor 2. Alternate splicing results in multiple transcript variants."[54]

  1. NP_001305769.1 leucine zipper protein 4 isoform 2: "Transcript Variant: This variant (2) lacks an exon in the 5' coding region which results in the use of a an alternate 5' most exon and a frameshift in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus compared to isoform 1."[54]
  2. NP_057467.1 leucine zipper protein 4 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."[54]

Gene ID: 51776 is MAP3K20 mitogen-activated protein kinase kinase kinase 20 aka ZAK on 2q31.1: "This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized."[55]

  1. NP_057737.2 mitogen-activated protein kinase kinase kinase 20 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1, also referred to as MRK-alpha and MLTK-alpha)."[55]
  2. NP_598407.1 mitogen-activated protein kinase kinase kinase 20 isoform 2: "Transcript Variant: This variant (2) lacks several exons in the coding region and contains a different 3' exon compared to variant 1. The resulting protein (isoform 2, also referred to as MRK-beta, MLTK-beta and MLK7) is shorter and has a distinct C-terminus compared to isoform 1."[55]

Gene ID: 54585 is LZTFL1 leucine zipper transcription factor like 1 on 3p21.31: "This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. Alternative splicing of this gene results in multiple transcript variants."[56]

  1. NP_001263307.1 leucine zipper transcription factor-like protein 1 isoform 2: "Transcript Variant: This variant (2) contains a distinct 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at a downstream in-frame AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1."[56]
  2. NP_001263308.1 leucine zipper transcription factor-like protein 1 isoform 3: "Transcript Variant: This variant (3) contains a distinct 5' UTR, has multiple coding region differences, and initiates translation at an alternate start codon compared to variant 1. The encoded isoform (3) is shorter and has distinct N- and C-termini, compared to isoform 1."[56]
  3. NP_065080.1 leucine zipper transcription factor-like protein 1 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."[56]

Gene ID: 55198 is APPL2 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 on 12q23.3: "The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome."[57]

  1. NP_001238833.1 DCC-interacting protein 13-beta isoform 2: "Transcript Variant: This variant (2) has an additional in-frame segment in the coding region, compared to variant 1. The resulting isoform 2 is longer than isoform 1."[57]
  2. NP_001238834.1 DCC-interacting protein 13-beta isoform 3: "Transcript Variant: This variant (3) differs in the 5' exon, which results in a downstream AUG start codon, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1."[57]
  3. NP_060641.2 DCC-interacting protein 13-beta isoform 1: "Transcript Variant: This variant (1) encodes the predominant isoform (1)."[57]

Gene ID: 55509 is BATF3 basic leucine zipper ATF-like transcription factor 3 on 1q32.3: "This gene encodes a member of the basic leucine zipper protein family. The encoded protein functions as a transcriptional repressor when heterodimerizing with JUN. The protein may play a role in repression of interleukin-2 and matrix metalloproteinase-1 transcription."[58]

Gene ID: 56169 is GSDMC gasdermin C aka melanoma-derived leucine zipper-containing extranuclear factor on 8q24.21.[59]

Gene ID: 57594 is HOMEZ homeobox and leucine zipper encoding on 14q11.2.[60]

Gene ID: 60468 is BACH2 BTB domain and CNC homolog 2 on 6q15.[61]

  1. NP_001164265.1 transcription regulator protein BACH2: "Transcript Variant: This variant (2) lacks two exons in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein."[61]
  2. NP_068585.1 transcription regulator protein BACH2: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."[61]

Gene ID: 84247 is RTL6 retrotransposon Gag like 6 aka leucine zipper protein down-regulated in cancer cells-like on 22q13.31.[62]

Gene ID: 84328 is LZIC leucine zipper and CTNNBIP1 domain containing on 1p36.22.[63]

  1. NP_001303902.1 protein LZIC isoform a: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a)."[63]

Gene ID: 84445 is LZTS2 leucine zipper tumor suppressor 2 on 10q24.31: "The protein encoded by this gene belongs to the leucine zipper tumor suppressor family of proteins, which function in transcription regulation and cell cycle control. This family member can repress beta-catenin-mediated transcriptional activation and is a negative regulator of the Wnt signaling pathway. It negatively regulates microtubule severing at centrosomes, and is necessary for central spindle formation and cytokinesis completion. It is implicated in cancer, where it may inhibit cell proliferation and decrease susceptibility to tumor development. Alternative splicing of this gene results in multiple transcript variants."[64]

  1. NP_001305028.1 leucine zipper putative tumor suppressor 2 isoform a: "Transcript Variant: This variant (2) contains an alternate 5' terminal exon and it thus differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 all encode the same isoform (a)."[64]
  2. NP_001305029.1 leucine zipper putative tumor suppressor 2 isoform a: "Transcript Variant: This variant (3) contains an alternate 5' terminal exon and it thus differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 all encode the same isoform (a)."[64]
  3. NP_001305030.1 leucine zipper putative tumor suppressor 2 isoform b: "Transcript Variant: This variant (4) lacks an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a. This variant has an incomplete 5' UTR because there are no 5'-complete transcripts representing it, and there is splicing ambiguity at the 5' end of the gene."[64]
  4. NP_115805.1 leucine zipper putative tumor suppressor 2 isoform a: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a). Variants 1, 2 and 3 all encode isoform a."[64]

Gene ID: 84654 is SPZ1 spermatogenic leucine zipper 1 on 5q14.1: "This gene encodes a bHLH-zip transcription factor which functions in the mitogen-activate protein kinase (MAPK) signaling pathway. Because of its role in the upregulation of cell proliferation and tumorigenesis, this gene may serve as a target for Ras-induced tumor treatments."[65]

Gene ID: 116071 is BATF2 basic leucine zipper ATF-like transcription factor 2 on 11q13.1.[66]

  1. NP_001287736.1 basic leucine zipper transcriptional factor ATF-like 2 isoform 2: "Transcript Variant: This variant (2) has an alternate exon in place of the first two exons compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1."[66]
  2. NP_001287737.1 basic leucine zipper transcriptional factor ATF-like 2 isoform 3: "Transcript Variant: This variant (3) has an alternate exon in place of the first two exons compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1."[66]
  3. NP_612465.3 basic leucine zipper transcriptional factor ATF-like 2 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[66]

Gene ID: 136991 is ASZ1 ankyrin repeat, SAM and basic leucine zipper domain containing 1 on 7q31.2.[67]

  1. NP_001288750.1 ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 isoform 2: "Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1."[67]
  2. NP_001288751.1 ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 isoform 3: "Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream start codon compared to variant 1. It encodes isoform 3 which has a shorter N-terminus compared to isoform 1."[67]
  3. NP_570124.1 ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[67]

Gene ID: 137994 is LETM2 leucine zipper and EF-hand containing transmembrane protein 2 on 8p11.23.[68]

  1. NP_001186588.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 1: "Transcript Variant: This variant (1) encodes isoform (1)."[68]
  2. NP_001186589.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1. Variants 3 and 4 enocode the same isoform (3)."[68]
  3. NP_001273716.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 3: "Transcript Variant: This variant (4) uses two alternate splice sites in the 5' UTR which results in the use of a downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1. Variants 3 and 4 enocode the same isoform (3)."[68]
  4. NP_001273748.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 4: "Transcript Variant: This variant (5) uses two alternate splice sites in the coding region which results in the use of an upstream AUG, compared to variant 1. The encoded isoform (4) has a longer N-terminus compared to isoform 1."[68]
  5. NP_001273750.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 5: "Transcript Variant: This variant (6) differs in both UTR's and the coding region and uses an alternate start codon, compared to variant 1. This results in an isoform (5) that is shorter and has distinct N- and C-termini, compared to isoform 1."[68]
  6. NP_001317444.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 6 [variant 7].[68]
  7. NP_001350133.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 7 precursor [variant 8].[68]
  8. NP_001350134.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 3 [variant 9].[68]
  9. NP_653253.1 LETM1 domain-containing protein LETM2, mitochondrial isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."[68]

Gene ID: 338645 is LUZP2 leucine zipper protein 2 on 11p14.3: "This gene encodes a leucine zipper protein. This protein is deleted in some patients with Wilms tumor-Aniridia-Genitourinary anomalies-mental Retardation (WAGR) syndrome. Alternate splicing results in multiple transcript variants."[69]

  1. NP_001009909.2 leucine zipper protein 2 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[69]
  2. NP_001238937.1 leucine zipper protein 2 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and lacks a portion of the 5' coding region, compared to variant 1. These differences causes translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1."[69]
  3. NP_001238939.1 leucine zipper protein 2 isoform 3: "Transcript Variant: This variant (3) lacks two in-frame exons in the coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1."[69]

X box nuclear factor genes

Gene ID: 4799 is NFX1 nuclear transcription factor, X-box binding 1 on 9p13.3: "MHC class II gene expression is controlled primarily at the transcriptional level by transcription factors that bind to the X and Y boxes, two highly conserved elements in the proximal promoter of MHC class II genes. The protein encoded by this gene is a transcriptional repressor capable of binding to the conserved X box motif of HLA-DRA and other MHC class II genes in vitro. The protein may play a role in regulating the duration of an inflammatory response by limiting the period in which class II MHC molecules are induced by IFN-gamma. Three alternative splice variants, each of which encodes a different isoform, have been identified."[70]

  1. NP_001305687.1 transcriptional repressor NF-X1 isoform 4: "Transcript Variant: This variant (4) uses an alternate in-frame splice site in an internal exon, compared to variant 1. It encodes isoform 4 which is longer than isoform 1."[70]
  2. NP_002495.2 transcriptional repressor NF-X1 isoform 1: "Transcript Variant: This variant (1) encodes isoform 1."[70]
  3. NP_667345.1 transcriptional repressor NF-X1 isoform 3: "Transcript Variant: This variant (3) utilizes an alternate 3' terminal exon compared to variant 1 and encodes the shortest isoform (3), with a unique C-terminus."[70]

Nuclear factor genes

Gene ID: 4790 is NFKB1 nuclear factor kappa B subunit 1 on 4q24: "This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed."[71]

  1. NP_001158884.1 nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein: "Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 amino acid shorter than isoform 1. Variants 2 and 3 encode the same isoform (2)."[71]
  2. NP_001306155.1 nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein: "Transcript Variant: This variant (3) differs in its 5' UTR and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 amino acid shorter than isoform 1. Variants 2 and 3 encode the same isoform (2)."[71]
  3. NP_003989.2 nuclear factor NF-kappa-B p105 subunit isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). This isoform (1) may undergo proteolytic processing similar to that of isoform 2."[71]

Gene ID: 4791 is NFKB2 nuclear factor kappa B subunit 2 on 10q24.32: "This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants."[72]

  1. NP_001070962.1 nuclear factor NF-kappa-B p100 subunit isoform a: "Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1 and 5 both encode the same isoform (a)."[72]
  2. NP_001248332.1 nuclear factor NF-kappa-B p100 subunit isoform b: "Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a. Variants 2, 3, and 4 encode the same isoform (b)."[72]
  3. NP_001275653.1 nuclear factor NF-kappa-B p100 subunit isoform b: "Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a. Variants 2, 3, and 4 encode the same isoform (b)."[72]
  4. NP_001309863.1 nuclear factor NF-kappa-B p100 subunit isoform a: "Transcript Variant: This variant (5) and variant 1 both encode the same isoform (a)."[72]
  5. NP_001309864.1 nuclear factor NF-kappa-B p100 subunit isoform c [variant 6].[72]
  6. NP_002493.3 nuclear factor NF-kappa-B p100 subunit isoform b: "Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a. Variants 2, 3, and 4 encode the same isoform (b)."[72]

Gene ID: 4792 is NFKBIA NFKB inhibitor alpha aka major histocompatibility complex enhancer-binding protein [mitotic arrest deficient 3] MAD3 on 14q13.2: "This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease."[73]

Gene ID: 4793 is NFKBIB NFKB inhibitor beta on 19q13.2: "The protein encoded by this gene belongs to the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B, which translocates to the nucleus to function as a transcription factor. Alternatively spliced transcript variants have been found for this gene."[74]

  1. NP_001230045.1 NF-kappa-B inhibitor beta isoform 2: "Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame downstream AUG, and a shorter isoform (2) compared to isoform 1."[74]
  2. NP_001356628.1 NF-kappa-B inhibitor beta isoform 3 [variant 4].[74]
  3. NP_001356629.1 NF-kappa-B inhibitor beta isoform 4 [variant 5].[74]
  4. NP_002494.2 NF-kappa-B inhibitor beta isoform 1: "Transcript Variant: This variant (1) represents the predominant transcript and encodes the longest isoform (1)."[74]

Gene ID: 4794 is NFKBIE NFKB inhibitor epsilon on 6p21.1: "The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus."[75]

Gene ID: 4795 is NFKBIL1 NFKB inhibitor like 1 on 6p21.33: "This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene."[76]

  1. NP_001138433.1 NF-kappa-B inhibitor-like protein 1 isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."[76]
  2. NP_001138434.1 NF-kappa-B inhibitor-like protein 1 isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1."[76]
  3. NP_001138435.1 NF-kappa-B inhibitor-like protein 1 isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1."[76]
  4. NP_004998.3 NF-kappa-B inhibitor-like protein 1 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[76]

Gene ID: 4796 is TONSL tonsoku like, DNA repair protein aka nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2 on 8q24.3: "The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus."[77]

Gene ID: 4798 is NFRKB nuclear factor related to kappaB binding protein on 11q24.3.[78]

  1. NP_001137307.1 nuclear factor related to kappa-B-binding protein isoform 1: "Transcript Variant: This variant (1) represents the longer transcript but encodes the shorter isoform (1)."[78]
  2. NP_006156.2 nuclear factor related to kappa-B-binding protein isoform 2: "Transcript Variant: This variant (2) represents use of an alternate promoter, differs in the 5' UTR and 5' coding region, and uses an alternate in-frame splice site in the central coding region, compared to variant 1. The resulting isoform (2) has a longer N-terminus and includes an additional internal segment, compared to isoform 1."[78]

Gene ID: 4899 is NRF1 nuclear respiratory factor 1 on 7q32.2: "This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1."[79]

  1. NP_001035199.1 nuclear respiratory factor 1 isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 3. The encoded protein (isoform 1) is shorter, compared to isoform 2. Variants 1 and 2 encode the same protein (isoform 1)."[79]
  2. NP_001280092.1 nuclear respiratory factor 1 isoform 2: "Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (2)."[79]
  3. NP_001280093.1 nuclear respiratory factor 1 isoform 3: "Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the coding region, and initiates translation at a downstream start codon, compared to variant 3. The encoded protein (isoform 3) is shorter, compared to isoform 2."[79]
  4. NP_005002.3 nuclear respiratory factor 1 isoform 1: "Transcript Variant: This variant (1) differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 3. The encoded protein (isoform 1) is shorter, compared to isoform 2. Variants 1 and 2 encode the same protein (isoform 1)."[79]

Gene ID: 5970 is RELA RELA proto-oncogene, NF-kB subunit, aka NFKB3 on 11q13.1: "NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene."[80]

  1. NP_001138610.1 transcription factor p65 isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site at one of the coding exons compared to transcript variant 1. This results in a shorter isoform (2) missing a 3 aa segment compared to isoform 1."[80]
  2. NP_001230913.1 transcription factor p65 isoform 3: "Transcript Variant: This variant (3) uses an alternate in-frame splice site at the 5' end of the last exon compared to variant 1. The resulting isoform (3) lacks an alternate internal segment compared to isoform 1."[80]
  3. NP_001230914.1 transcription factor p65 isoform 4: "Transcript Variant: This variant (4) lacks an alternate internal in-frame segment in the last exon compared to variant 1. The resulting isoform (4) lacks an alternate internal segment compared to isoform 1."[80]
  4. NP_068810.3 transcription factor p65 isoform 1: "Transcript Variant: This variant (1) represents the predominant transcript and encodes the longer isoform (1)."[80]

Consensus sequences

Hepatic nuclear factor (HNF) DNA-binding domain (DBD): (A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T).

Nuclear factor 1 (NF-1) DNA binding domain: TTGGCXXXXXGCCAA.

Nuclear factor 𝜿B DNA binding: CCCCTAAGGGG.

Nuclear factor of activated T cell gene transcriptions (NFAT): GGAAAA.

Nuclear factor Y apparent consensus sequence: CAATGG(A/C)(A/G).

Hypotheses

  1. A1BG has no CCAAT-boxes in either promoter.
  2. A1BG is not transcribed by a CCAAT-box.
  3. CCAAT-box does not participate in the transcription of A1BG.

CCAAT samplings

For the Basic programs testing consensus sequence 5'-CCAAT-3' (starting with SuccessablesCCAT.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-CCAAT-3', 0.
  2. negative strand, positive direction, looking for 5'-CCAAT-3', 1, 5'-CCAAT-3' at 2908.
  3. positive strand, negative direction, looking for 5'-CCAAT-3', 1, 5'-CCAAT-3' at 2848.
  4. positive strand, positive direction, looking for 5'-CCAAT-3', 1, 5'-CCAAT-3' at 3024.
  5. complement, negative strand, negative direction, looking for 5'-GGTTA-3', 1, 5'-GGTTA-3' at 2848.
  6. complement, negative strand, positive direction, looking for 5'-GGTTA-3', 1, 5'-GGTTA-3' at 3024.
  7. complement, positive strand, negative direction, looking for 5'-GGTTA-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-GGTTA-3', 1, 5'-GGTTA-3' at 2908.
  9. inverse complement, negative strand, negative direction, looking for 5'-ATTGG-3', 1, 5'-ATTGG-3' at 614.
  10. inverse complement, negative strand, positive direction, looking for 5'-ATTGG-3', 1, 5'-ATTGG-3' at 24.
  11. inverse complement, positive strand, negative direction, looking for 5'-ATTGG-3', 3, 5'-ATTGG-3' at 3529, 5'-ATTGG-3' at 1045, 5'-ATTGG-3' at 643.
  12. inverse complement, positive strand, positive direction, looking for 5'-ATTGG-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-TAACC-3', 3, 5'-TAACC-3' at 3529, 5'-TAACC-3' at 1045, 5'-TAACC-3' at 643.
  14. inverse negative strand, positive direction, looking for 5'-TAACC-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-TAACC-3', 1, 5'-TAACC-3' at 614.
  16. inverse positive strand, positive direction, looking for 5'-TAACC-3', 1, 5'-TAACC-3' at 24.

CCAAT distal promoters

Negative strand, negative direction,: 5'-ATTGG-3' at 614, and complement.

Positive strand, negative direction: 5'-ATTGG-3' at 3529, 5'-CCAAT-3' at 2848, 5'-ATTGG-3' at 1045, 5'-ATTGG-3' at 643, and complement.

Negative strand, positive direction: 5'-CCAAT-3' at 2908, 5'-ATTGG-3' at 24, and complement.

Positive strand, positive direction: 5'-CCAAT-3' at 3024, and complement.

NF-1 samplings

Copying an apparent consensus sequence for the NF1 TTGGCA and putting it in "⌘F" finds none located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TTGGCNNNNNGCCAA (starting with SuccessablesNF1.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for TTGGCNNNNNGCCAA, 0.
  2. positive strand, negative direction, looking for TTGGCNNNNNGCCAA, 0.
  3. positive strand, positive direction, looking for TTGGCNNNNNGCCAA, 0.
  4. negative strand, positive direction, looking for TTGGCNNNNNGCCAA, 0.
  5. complement, negative strand, negative direction, looking for AACCGNNNNNCGGTT, 0.
  6. complement, positive strand, negative direction, looking for AACCGNNNNNCGGTT, 0.
  7. complement, positive strand, positive direction, looking for AACCGNNNNNCGGTT, 0.
  8. complement, negative strand, positive direction, looking for AACCGNNNNNCGGTT, 0.
  9. inverse complement, negative strand, negative direction, looking for TTGGCNNNNNGCCAA, 0.
  10. inverse complement, positive strand, negative direction, looking for TTGGCNNNNNGCCAA, 0.
  11. inverse complement, positive strand, positive direction, looking for TTGGCNNNNNGCCAA, 0.
  12. inverse complement, negative strand, positive direction, looking for TTGGCNNNNNGCCAA, 0.
  13. inverse negative strand, negative direction, looking for AACCGNNNNNCGGTT, 0.
  14. inverse positive strand, negative direction, looking for AACCGNNNNNCGGTT, 0.
  15. inverse positive strand, positive direction, looking for AACCGNNNNNCGGTT, 0.
  16. inverse negative strand, positive direction, looking for AACCGNNNNNCGGTT, 0.

NF-1 first factor samplings

For the Basic programs testing consensus sequence TTGGC (starting with SuccessablesFirstFactor.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for TTGGC, 0.
  2. positive strand, negative direction, looking for TTGGC, 3, TTGGC at 4098, TTGGC at 3947, TTGGC at 644.
  3. positive strand, positive direction, looking for TTGGC, 2, TTGGC at 3912, TTGGC at 2149.
  4. negative strand, positive direction, looking for TTGGC, 1, TTGGC at 2186.

Gene ID: 1 has TTGGC occurring as follows: on nn there are none, on pn there are none within TSS ± 50, but at other locations -2211 TTGGC -2207, +1132 TTGGC +1136 and +1240 TTGGC +1244, in the positive direction the same result occurred that there were none within TSS ± 50, on np at -2161 TTGGC -2157 and on pp at -2217 TTGGC -2213 and -454 TTGGC -450.

NF-1 second factor samplings

For the Basic programs testing consensus sequence GCCAA (starting with SuccessablesSecondFactor.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for GCCAA, 1, GCCAA at 2233.
  2. positive strand, negative direction, looking for GCCAA, 8, GCCAA at 3272, GCCAA at 2609, GCCAA at 1636, GCCAA at 1202, GCCAA at 873, GCCAA at 691, GCCAA at 555, and GCCAA at 418.
  3. positive strand, positive direction, looking for GCCAA, 1, GCCAA at 3489.
  4. negative strand, positive direction, looking for GCCAA, 3, GCCAA at 2907, GCCAA at 2825, and GCCAA at 2011.

Gene ID: 1 has GCCAA occurring as follows: on nn at -122 GCCAA -618, on pn at -2437 GCCAA -2433, -2300 GCCAA -2296, -2162 GCCAA -2158, -1982 GCCAA -1978, -1653 GCCAA -1649, -1219 GCCAA -1215, -246 GCCAA -242 and +417 GCCAA +421, and on np at -2355 GCCAA -2351, -1541 GCCAA -1537, and -1459 GCCAA -1455, and pp at -877 GCCAA -873. None are close enough to form Order 75 as found by computer analysis, or occur on either side of A1BG within the possible TSS ranges of ± 50.

NF𝜿B samplings

Copying an apparent core consensus sequence for the NF𝛋B of GAATTC and putting it in "⌘F" finds three cores located between ZSCAN22 and none between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence CCCCTAAGGGG (starting with SuccessablesNF𝜿B.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for CCCCTAAGGGG, 0.
  2. positive strand, negative direction, looking for CCCCTAAGGGG, 0.
  3. positive strand, positive direction, looking for CCCCTAAGGGG, 0.
  4. negative strand, positive direction, looking for CCCCTAAGGGG, 0.
  5. complement, negative strand, negative direction, looking for GGGGATTCCCC, 0.
  6. complement, positive strand, negative direction, looking for GGGGATTCCCC, 0.
  7. complement, positive strand, positive direction, looking for GGGGATTCCCC, 0.
  8. complement, negative strand, positive direction, looking for GGGGATTCCCC, 0.
  9. inverse complement, negative strand, negative direction, looking for CCCCTTAGGGG, 0.
  10. inverse complement, positive strand, negative direction, looking for CCCCTTAGGGG, 0.
  11. inverse complement, positive strand, positive direction, looking for CCCCTTAGGGG, 0.
  12. inverse complement, negative strand, positive direction, looking for CCCCTTAGGGG, 0.
  13. inverse negative strand, negative direction, looking for GGGGAATCCCC, 0.
  14. inverse positive strand, negative direction, looking for GGGGAATCCCC, 0.
  15. inverse positive strand, positive direction, looking for GGGGAATCCCC, 0.
  16. inverse negative strand, positive direction, looking for GGGGAATCCCC, 0.

NF𝜿B (Sato) samplings

For the Basic programs testing consensus sequence GAATTC (starting with SuccessablesNF𝜿BS.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction: 3, GAATTC at 4408, GAATTC at 4164, GAATTC at 319.
  2. positive strand, negative direction: 2, GAATTC at 1522, GAATTC at 1415.
  3. negative strand, positive direction: 0.
  4. positive strand, positive direction: 1, GAATTC at 1539.
  5. inverse complement (ci), same as above.

NFKBS (4560-2846) UTRs

  1. Negative strand, negative direction: GAATTC at 4408, GAATTC at 4164.

NFKBS negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: GAATTC at 319.
  2. positive strand, negative direction: GAATTC at 1522, GAATTC at 1415.

NFKBS positive direction (4050-1) distal promoters

  1. Positive strand, positive direction: GAATTC at 1539.

NF𝜿BS random dataset samplings

  1. NF𝜿BSr0: 0.
  2. NF𝜿BSr1: 3, GAATTC at 3089, GAATTC at 2989, GAATTC at 2978.
  3. NF𝜿BSr2: 0.
  4. NF𝜿BSr3: 0.
  5. NF𝜿BSr4: 1, GAATTC at 394.
  6. NF𝜿BSr5: 3, GAATTC at 3340, GAATTC at 560, GAATTC at 448.
  7. NF𝜿BSr6: 3, GAATTC at 3952, GAATTC at 2570, GAATTC at 501.
  8. NF𝜿BSr7: 2, GAATTC at 4108, GAATTC at 2558.
  9. NF𝜿BSr8: 0.
  10. NF𝜿BSr9: 1, GAATTC at 1939.

NF𝜿BSr arbitrary (evens) (4560-2846) UTRs

  1. NF𝜿BSr6: GAATTC at 3952.

NF𝜿BSr alternate (odds) (4560-2846) UTRs

  1. NF𝜿BSr1: GAATTC at 3089, GAATTC at 2989, GAATTC at 2978.
  2. NF𝜿BSr5: GAATTC at 3340.
  3. NF𝜿BSr7: GAATTC at 4108.

NFKBSr arbitrary positive direction (odds) (4265-4050) proximal promoters

  1. NF𝜿BSr7: GAATTC at 4108.

NF𝜿BSr arbitrary negative direction (evens) (2596-1) distal promoters

  1. NF𝜿BSr4: GAATTC at 394.
  2. NF𝜿BSr6: GAATTC at 2570, GAATTC at 501.

NFKBSr alternate negative direction (odds) (2596-1) distal promoters

  1. NF𝜿BSr5: GAATTC at 560, GAATTC at 448.
  2. NF𝜿BSr7: GAATTC at 2558.
  3. NF𝜿BSr9: GAATTC at 1939.

NF𝜿BSr arbitrary positive direction (odds) (4050-1) distal promoters

  1. NF𝜿BSr1: GAATTC at 3089, GAATTC at 2989, GAATTC at 2978.
  2. NF𝜿BSr5: GAATTC at 3340, GAATTC at 560, GAATTC at 448.
  3. NF𝜿BSr7: GAATTC at 2558.
  4. NF𝜿BSr9: GAATTC at 1939.

NF𝜿BSr alternate positive direction (evens) (4050-1) distal promoters

  1. NF𝜿BSr4: GAATTC at 394.
  2. NF𝜿BSr6: GAATTC at 3952, GAATTC at 2570, GAATTC at 501.

NF𝜿BS analysis and results

Binding site for NF𝛋B in humans (GGAATTCCCC) with a core of (GAATTC), Sp-1 (CCGCCCC), 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element (TRE) (TGAGTCA), and GC box (GGGCGG).[81]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 2 2 1 1 ± 1 (--2,+-0)
Randoms UTR arbitrary negative 1 10 0.1 0.3
Randoms UTR alternate negative 5 10 0.5 0.3
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 0 10 0 0
Randoms Core alternate positive 0 10 0 0
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 0 10 0 0
Randoms Proximal alternate negative 0 10 0 0
Reals Proximal positive 0 2 0 0
Randoms Proximal arbitrary positive 1 10 0.1 0.05
Randoms Proximal alternate positive 0 10 0 0.05
Reals Distal negative 3 2 1.5 1.5 ± 0.5 (--1,+-2)
Randoms Distal arbitrary negative 3 10 0.3 0.35
Randoms Distal alternate negative 4 10 0.4 0.35
Reals Distal positive 1 2 0.5 0.5 ± 0.5 (-+0,++1)
Randoms Distal arbitrary positive 8 10 0.8 0.6
Randoms Distal alternate positive 4 10 0.4 0.6

Comparison:

The occurrences of real NF𝜿BSs are greater than the randoms. This suggests that the real NF𝜿BSs are likely active or activable.

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

See also

References

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  32. Nantel A, Quatrano RS (December 1996). "Characterization of three rice basic/leucine zipper factors, including two inhibitors of EmBP-1 DNA binding activity". The Journal of Biological Chemistry. 271 (49): 31296–305. doi:10.1074/jbc.271.49.31296. PMID 8940135.
  33. 33.0 33.1 33.2 RefSeq (May 2009). "BACH1 BTB domain and CNC homolog 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  34. 34.0 34.1 RefSeq (October 2009). "LETM1 leucine zipper and EF-hand containing transmembrane protein 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  35. 35.0 35.1 35.2 35.3 RefSeq (13 March 2020). "NFE2 nuclear factor, erythroid 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  36. 36.0 36.1 36.2 36.3 RefSeq (July 2008). "NFE2L1 nuclear factor, erythroid 2 like 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  37. 37.0 37.1 37.2 37.3 37.4 37.5 37.6 37.7 37.8 RefSeq (September 2015). "NFE2L2 nuclear factor, erythroid 2 like 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  38. 38.0 38.1 38.2 38.3 RefSeq (February 2014). "NFIL3 nuclear factor, interleukin 3 regulated [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  39. cd14694 (2 March 2014). "Conserved Protein Domain Family bZIP_NFIL3". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  40. 40.0 40.1 40.2 40.3 40.4 RefSeq (29 March 2020). "NRL neural retina leucine zipper [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  41. RefSeq (29 March 2020). "RELB RELB proto-oncogene, NF-kB subunit [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  42. S. Lu (2020). "Conserved Protein Domain Family RelB_leu_zip". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  43. 43.0 43.1 43.2 RefSeq (December 2008). "LUZP1 leucine zipper protein 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 May 2020.
  44. RefSeq (29 March 2020). "LZTR1 leucine zipper like transcription regulator 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 May 2020.
  45. 45.0 45.1 45.2 45.3 RefSeq (13 March 2020). "BLZF1 basic leucine zipper nuclear factor 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 May 2020.
  46. 46.0 46.1 46.2 46.3 46.4 46.5 46.6 46.7 46.8 46.9 RefSeq (3 May 2020). "BZW1 basic leucine zipper and W2 domains 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 May 2020.
  47. 47.0 47.1 47.2 47.3 47.4 47.5 47.6 47.7 47.8 47.9 HGNC (5 April 2020). "MELK maternal embryonic leucine zipper kinase [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  48. RefSeq (July 2008). "BATF basic leucine zipper ATF-like transcription factor [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  49. Conserved Protein Domain Family (July 2020). "Basic leucine zipper (bZIP) domain of BATF proteins: a DNA-binding and dimerization domain". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  50. 50.0 50.1 50.2 RefSeq (November 2009). "LZTS1 leucine zipper tumor suppressor 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  51. RefSeq (July 2008). "LDOC1 LDOC1 regulator of NFKB signaling [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  52. RefSeq (July 2008). "APPL1 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 May 2020.
  53. 53.0 53.1 53.2 53.3 53.4 53.5 RefSeq (3 May 2020). "BZW2 basic leucine zipper and W2 domains 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  54. 54.0 54.1 54.2 RefSeq (January 2016). "LUZP4 leucine zipper protein 4 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  55. 55.0 55.1 55.2 RefSeq (July 2008). "MAP3K20 mitogen-activated protein kinase kinase kinase 20 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  56. 56.0 56.1 56.2 56.3 RefSeq (February 2013). "LZTFL1 leucine zipper transcription factor like 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  57. 57.0 57.1 57.2 57.3 RefSeq (October 2011). "APPL2 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  58. RefSeq (February 2009). "BATF3 basic leucine zipper ATF-like transcription factor 3 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  59. RefSeq (20 March 2020). "GSDMC gasdermin C aka melanoma-derived leucine zipper-containing extranuclear factor [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  60. RefSeq (13 March 2020). "HOMEZ homeobox and leucine zipper encoding [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  61. 61.0 61.1 61.2 HGNC (3 May 2020). "BACH2 BTB domain and CNC homolog 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  62. HGNC (13 March 2020). "RTL6 retrotransposon Gag like 6 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  63. 63.0 63.1 HGNC (13 March 2020). "LZIC leucine zipper and CTNNBIP1 domain containing [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 9 May 2020.
  64. 64.0 64.1 64.2 64.3 64.4 RefSeq (December 2015). "LZTS2 leucine zipper tumor suppressor 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 10 May 2020.
  65. RefSeq (October 2011). "SPZ1 spermatogenic leucine zipper 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 10 May 2020.
  66. 66.0 66.1 66.2 66.3 HGNC (13 March 2020). "BATF2 basic leucine zipper ATF-like transcription factor 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 11 May 2020.
  67. 67.0 67.1 67.2 67.3 HGNC (13 March 2020). "ASZ1 ankyrin repeat, SAM and basic leucine zipper domain containing 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 12 May 2020.
  68. 68.0 68.1 68.2 68.3 68.4 68.5 68.6 68.7 68.8 68.9 HGNC (13 March 2020). "LETM2 leucine zipper and EF-hand containing transmembrane protein 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 12 May 2020.
  69. 69.0 69.1 69.2 69.3 RefSeq (October 2011). "LUZP2 leucine zipper protein 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 13 May 2020.
  70. 70.0 70.1 70.2 70.3 RefSeq (July 2008). "NFX1 nuclear transcription factor, X-box binding 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  71. 71.0 71.1 71.2 71.3 RefSeq (February 2016). "NFKB1 nuclear factor kappa B subunit 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  72. 72.0 72.1 72.2 72.3 72.4 72.5 72.6 RefSeq (December 2013). "NFKB2 nuclear factor kappa B subunit 2 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  73. RefSeq (August 2011). "NFKBIA NFKB inhibitor alpha [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 28 March 2020.
  74. 74.0 74.1 74.2 74.3 74.4 RefSeq (July 2008). "NFKBIB NFKB inhibitor beta [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  75. RefSeq (September 2011). "NFKBIE NFKB inhibitor epsilon [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  76. 76.0 76.1 76.2 76.3 76.4 RefSeq (January 2009). "NFKBIL1 NFKB inhibitor like 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  77. RefSeq (July 2008). "TONSL tonsoku like, DNA repair protein [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  78. 78.0 78.1 78.2 RefSeq (13 March 2020). "NFRKB nuclear factor related to kappaB binding protein [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 4 May 2020.
  79. 79.0 79.1 79.2 79.3 79.4 RefSeq (May 2014). "NRF1 nuclear respiratory factor 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 6 May 2020.
  80. 80.0 80.1 80.2 80.3 80.4 RefSeq (September 2011). "RELA RELA proto-oncogene, NF-kB subunit [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  81. Hiroshi Sato, Megumi Kita, and Motoharu Seiki (5 November 1993). "v-Src Activates the Expression of 92-kDa Type IV Collagenase Gene through the AP-1 Site and the GT Box Homologous to Retinoblastoma Control Elements" (PDF). The Journal of Biological Chemistry. 268 (31): 23460–8. PMID 8226872. Retrieved 13 August 2020.

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