TMEM98

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene.[1][2] The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.[3]


Gene

This gene is found on the plus strand of chromosome 17 at locus 17q11.2.[2] It spans from base pairs 31,254,928 to 31,272,124.[4]

Variants

There are two known transcript variants that encode for TMEM98. Variant one corresponds to the longer of the two, has 8 exons, and is 1808 bases in length.[5] Variant two codes for the same protein, but is slightly shorter at exon 2 and is missing exon 3; it is 1732 bases long.[6] This missing region corresponds to 85 base pairs near the end of the 5' UTR.[6] Variant one is more abundant than Variant two with 17 times the amount mRNA extracted in various human tissue experiments.[7]


Evolution

Paralogs

There are no known paralogs for TMEM98.[4] While not functional, there are two pseudogenes found on chromosome 6 and 14 in Homo sapiens.[8]

Orthologs

Transmembrane protein 98 is highly conserved in fish, amphibians, reptiles, birds, and other non-human mammals. It is only slightly conserved and invertebrates and insects and is not found in bacteria, archaea, protists, plants, or fungi.

Genus and Species Common Name Class Accession Percent Identity
Pan paniscus Bonobo Mammalia XP_003818064.1 99%
Felis catus Common House Cat Mammalia XP_003996602 99%
Mus musculus Mouse Mammalia NP_083813.1 99%
Myotis davidii Mouse-Eared Bat Mammalia ELK33053.1 95%
Heterocephalus glaber Naked Mole Rat Mammalia EHB09150.1 94%
Anolis carolinensis Arboreal Lizard Reptilia XP_003222593 85%
Taeniopygia guttata Zebra Finch Aves XP_002193870.1 78%
Tetraodon nigrovirdis Green Spotten Puffer Fish Actinopterygii CAG07250.1 78%
Bombus impatiens Common Eastern Bubblebee Insecta XP_003489307.1 42%
Harpegnathos saltator Jumping Ant Insecta EFN84682.1 40%
Trichinella spiralis Nematode Parasite Annelida XP_003372303.1 37%

Phylogeny

The percent change over time graph was made using Time Tree.[9]

File:Phylogenetic Change Over Time of TMEM98.png
Percent Change Over Time

Protein

Transcript Variant one and two code for the same protein of 226 amino acids.[2] The protein is 24.6 kdal with an isoelectric point of 4.26.[10]


Domains

There is no signal peptide in this protein.[11] The transmembrane domain is 22 amino acids long and is located from amino acids 6-28. Amino acids on the N-terminus side are located outside of the cell, and amino acids on the C-terminius side are outside of the cell.[12]

The paralogous domain Grap2 and cyclin-D-interacting (pfam13324) spans from 81-151 and is highly conserved in orthologs.[13] This region is involved in the regulation of proliferation and cell differentiation using Grap2 and cyclin-d-mediated signaling pathways.[14]

Secondary Structure

TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10−7.[15]

Regulation

mRNA level

The promotor region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below.[16]

Transcription Factor Start End Strand Sequence
GC-box factors SP1/GC 58 74 + gtagGGGGtgtgtgttt
C2H2 zinc finger transcription factor 5 102 116 + tgtatgGGATggagt
C2H2 zinc finger transcription factor 2 48 70 - acacaCCCCctaccctgccatcc
Motif composed of binding sites for pluripotency or stem cell factors 151 169 + gggctctGCATttgtactc
Calcium-response element 352 362 + agaccGAGGca
CP2-erythrocyte Factor released to drosophila Elf1 II B 386 404 - cTCTGccactcactagcta
GC-box factors SP1/GC 500 516 + gcccgGGGCggggcgca
Metal induced transcription factor 505 519 - gcctGCGCcccgccc
KRAB domain zinc finger protein 57 543 555 + gtcTGCCgcccgg
Pleomorphic adenoma gene 567 589 + cgGGGGcgcgaggaaggggtgtt
CTCF and BORIS gene family, transcriptional regulators 615 641 + tgccccggccgccgGGGGgcctggcgg
EGR/nerve growth factor induced protein C and release factor 695 713 + gggcgcggGGGCgcgaggc
E2F-myc activator and cell cycle regulator 663 679 - ggcccgcgcCAAAtccc
RNA polymerase II transcription factor 670 676 - ccgCGCC
RNA polymerase II transcription factor 696 702 - ccgCGCC
Nuclear respiratory factor 1 694 710 - tcgcGCCCccgcgcccc
Selenocysteine tRNA activation factor 725 755 + ggccgcggcgcttCCCGgcatgctccgctgc
Nuclear respiratory factor 1 758 774 + gcccGCGCccgcgcccg
Histone nuclear factor P 771 783 + ccCGGActttgcc
Nuclear respiratory factor 1 759 775 - ccggGCGCgggcgcggg
RNA polymerase II transcription factor 886 892 - ccgCGCC

Possible Stem Loops The 5' UTR has two possible stem loops. These are located from 279-303 and 342-372. In the 3' UTR, there is a possible stem loop located from 1487-1502.[17]

microRNA Binding Sites There is one miRNA binding site in the 3' UTR as predicted using TargetScan.[18][19] This miRNA, has-miR-4782-3p, may play a role in breast cancer.[20]

Protein level

TMEM98 has 4 predicted glycation sites at amino acids 44, 118, 120, and 133.[21] There are serine phosphorylation sites at 60, 122, 124, 136, 145, and 191 and threonine phosphorylation sites at 55, 105, and 160.[22] These sites are all on the N-terminus side of the transmembrane region and are inside the cytosol of the cell.

Expression

TMEM98 is expressed highly in retina, adipose tissue, embryo, ovary, umbilical cord, uterus, prostate, large and small intestines, lung, medical olfactory epithelium, nasal organ, stomach, bladder, and adrenal gland tissues. It is expressed very low in fertilized egg, oocyte, B cell, skeletal muscle, tongue epidermis, and thymus tissues.

It is also more highly expressed later embryonic stages.[23]


Clinical aspects

Mutations in TMEM98 cause autosomal dominant nanophthalmos .[24]

References

  1. ↑ Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: TMEM98 transmembrane protein 98".
  3. ↑ Clark HF, Gurney AL, Abaya E, et al. (October 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
  4. ↑ 4.0 4.1 "Ensembl genome browser 75: Homo sapiens - Summary - Gene: TMEM98 (ENSG00000006042)".
  5. ↑ "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 1, - Nucleotide - NCBI".
  6. ↑ 6.0 6.1 "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 2, - Nucleotide - NCBI".
  7. ↑ "AceView: Gene:TMEM98, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView".
  8. ↑ "TMEM98 Gene - GeneCards | TMM98 Protein | TMM98 Antibody".
  9. ↑ "TimeTree :: The Timescale of Life".
  10. ↑ "SDSC Biology Workbench".
  11. ↑ "SignalP 4.1 Server".
  12. ↑ "harrier.nagahama-i-bio.ac.jp".
  13. ↑ "NCBI Conserved Domain Search".
  14. ↑ Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (July 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". J. Biol. Chem. 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854.
  15. ↑ "Welcome to NCBI Related Structure Search".
  16. ↑ "Genomatix - NGS Data Analysis & Personalized Medicine".
  17. ↑ "The Mfold Web Server | mfold.rit.albany.edu".
  18. ↑ "TargetScanHuman 6.2".
  19. ↑ Agarwal, Vikram; Bell, George W.; Nam, Jin-Wu; Bartel, David P. (2015-08-12). "Predicting effective microRNA target sites in mammalian mRNAs". eLife. 4: e05005. doi:10.7554/eLife.05005. ISSN 2050-084X. PMC 4532895. PMID 26267216.
  20. ↑ Persson H, Kvist A, Rego N, et al. (January 2011). "Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene". Cancer Res. 71 (1): 78–86. doi:10.1158/0008-5472.CAN-10-1869. PMID 21199797.
  21. ↑ "NetGlycate 1.0 Server".
  22. ↑ "NetPhos 2.0 Server".
  23. ↑ "Home - GEO Profiles - NCBI".
  24. ↑ Awadalla, M. S.; Burdon, K. P.; Souzeau, E; Landers, J; Hewitt, A. W.; Sharma, S; Craig, J. E. (2014). "Mutation in TMEM98 in a Large White Kindred with Autosomal Dominant Nanophthalmos Linked to 17p12-q12". JAMA Ophthalmology. 132: 970. doi:10.1001/jamaophthalmol.2014.946. PMID 24852644.
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