C7orf43

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
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C7orf43 (Chromosome 7 Open reading frame 43) is a protein that in human is encoded by the gene C7orf43. C7orf43 has no other human alias, but in mice can be found as BC037034.

Gene Locus

In humans, C7orf43 is located in the long arm of human chromosome 7 (7q22.1), and is on the negative (antisense) strand. Genes located around C7orf43 include GAL3ST4, LAMTOR4, GPC2. In humans, C7orf43 has 9 detected common single-nucleotide polymorphisms (SNPs), all of which are located in non-coding regions and thus do not affect amino acid sequence.

File:Geneneigbour.png

Gene neighbourhood of C7orf43 in human chromosome 7

mRNA

Splice variants

File:C7orf43 isoform 1 transcript.png

Primary transcript of C7orf43 isoform 1, showing 11 exons and 10 introns (NCBI Aceview:C7orf43)

C7orf43 encodes 2 isoforms, the longest being C7orf43 isoform 1, which is 2585 base pairs long and has with 11 exons and 10 introns. C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site. C7orf43 isoform 2 is 2085 base pairs long and encodes a protein of 311 amino acids. Two additional isoforms has been reported on several occasions, encoding for proteins with 199 and 206 amino acids.

Tissue expression

C7orf43 has a widespread moderate expression with tissue to tissue variability in humans and across mammalian species. The mouse C7orf43 ortholog has been shown to be ubiquitously expressed in the brain, as well as in the mouse embryonic central nervous system.

Regulations

C7orf43 has one promoter region upstream of its transcription site, as predicted by Genomatix. This promoter is 657 base pairs long and is located at position 99756182 to 99756838 in the negative strand of chromosome 7. There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors. The top 20 transcription binding sites as predicted by the ElDorado from Genomatix is listed in the following table.

Detailed Family Information	Detailed Matrix Information	Start Position	End Position	Anchor Position	Strand	Matrix Similarity Score	Sequence
Brachyury gene, mesoderm developmental factor	T-box transcription factor TBX20	617	645	631	+	1	agcagccggAGGTgtcgggaccctctgga
C2H2 zinc finger transcription factors 2	KRAB-containing zinc finger protein 300	596	618	607	+	1	ccggccgCCCCagccgggcgcag
Fork head domain factors	Alternative splicing variant of FOXP1, activated in ESCs	37	53	45	-	1	aaaaaaaAACAaccctt
Pleomorphic adenoma gene	Pleomorphic adenoma gene 1	411	433	422	-	1	gaGGGGgcggggtcccgctgctc
Pleomorphic adenoma gene	Pleomorphic adenoma gene 1	464	486	475	-	1	gaGGGGgcgtggccgccgaggcc
RNA polymerase II transcription factor II B	Transcription factor II B (TFIIB) recognition element	197	203	200	+	1	ccgCGCC
TGF-beta induced apoptosis proteins	Cysteine-serine-rich nuclear protein 1 (AXUD1, AXIN1 up-regulated 1)	73	79	76	-	1	AGAGtga
GC-Box factors SP1/GC	Stimulating protein 1, ubiquitous zinc finger transcription factor	418	434	426	-	0.998	ggaggGGGCggggtccc
Human and murine ETS1 factors	Ets variant 3	486	506	496	-	0.996	gagaaacaGGAAgcggaaggg
Krueppel like transcription factors	Gut-enriched Krueppel-like factor / KLF4	469	485	477	-	0.994	agggggcGTGGccgccg
Two-handed zinc finger homeodomain transcription factors	AREB6 (Atp1a1 regulatory element binding factor 6)	495	507	501	+	0.994	ttcctGTTTctct
Zinc finger transcription factor RU49, zinc finger proliferation 1 - Zipro1	Zinc finger transcription factor RU49 (zinc finger proliferation 1 - Zipro 1). RU49 exhibits a strong preference for binding to tandem repeats of the minimal RU49 consensus binding site.	522	528	525	+	0.994	cAGTAcc
Krueppel like transcription factors	Core promoter-binding protein (CPBP) with 3 Krueppel-type zinc fingers (KLF6, ZF9)	418	434	426	-	0.992	ggagGGGGcggggtccc
C2H2 zinc finger transcription factors 7	Zinc finger protein 263, ZKSCAN12 (zinc finger protein with KRAB and SCAN domains 12)	425	439	432	+	0.99	cgccccCTCCtccac
C2H2 zinc finger transcription factors 6	Zinc finger and BTB domain containing 7, Proto-oncogene FBI-1, Pokémon (secondary DNA binding preference)	252	264	258	-	0.989	caaGACCaccctg
Krueppel like transcription factors	Kruppel-like factor 7 (ubiquitous, UKLF)	416	432	424	-	0.989	agggGGCGgggtcccgc
GC-Box factors SP1/GC	Sp4 transcription factor	471	487	479	-	0.986	ggagggGGCGtggccgc
Krueppel like transcription factors	Gut-enriched Krueppel-like factor	137	153	145	+	0.986	gggctcAAAGgatcctc
Krueppel like transcription factors	Krueppel-like factor 2 (lung) (LKLF)	641	657	649	-	0.986	cgctaGGGTgggtccag
Human and murine ETS1 factors	Ets variant 1	6	26	16	-	0.984	ttctcccaGGAAgattctcca

Protein

Composition and Domains

The human protein C7orf43 has an isoelectric point of 8.94. C7orf43 also has a glycine-rich region spanning amino acids 54 through 134. Analysis using the SAPS tool from the SDSC Biology Workbench showed this glycine-rich region to not be conserved in terms of specific glycine residue positions, but is well conserved in overall glycine content in mammals and reptiles, although not in bony fishes. C7orf43 is mostly uncharged, and this neutral charge distribution is conserved in mammals and reptiles, but bony fishes have at least one negative charge cluster C7orf43 is predicted to have no signal peptide in its first 70 amino acid residues. However, it is predicted to have a vacuolar targeting motif starting at residue 258 in the human protein. This vacuolar targeting motif is shown to be conserved throughout mammals, reptiles, birds, amphibians, and bony fishes.

Evolutionary history

The C7orf43 protein has no paralogs in humans. However, C7orf43 orthologs can be found to be highly conserved in mammals, reptiles, and several species of bony fishes. C7orf43 is also conserved in birds, although several bird species lack parts of the N-terminus. No C7orf43 orthologs can be found outside the animal kingdom. The following table lists representative C7orf43 orthologs across multiple animal classes.

Strict orthologs

No.	Species	Common Name	Date of Divergence (MYA)	Accession No.	E-value	Length (aa)	Identity (%)	Similarity (%)
1	Homo sapiens	Human	-	NP_060745.3	0.0	580	100	100
2	Pan troglodytes	Common Chimpanzee	6.3	XP_009452032	0.0	580	99	100
3	Macaca mulatta	Macaque	29.0	XP_001102238	0.0	580	99	99
4	Cavia porcellus	Guinea pig	92.3	XP_003470051	0.0	580	98	98
5	Sus scrofa	Wild boar	94.2	XP_003124386	0.0	580	98	99
6	Odobenus rosmarus divergens	Walrus	94.2	XP_004399075	0.0	580	98	98
7	Tursiops truncates	Common bottlenose dolphin	94.2	XP_004315199	0.0	582	92	93
8	Echinops telfairi	Lesser hedgehog tenrec	98.7	XP_004705644	0.0	581	95	97
9	Dasypus novemcinctus	Nine-banded armadillo	104.2	XP_004457234	0.0	580	97	98
10	Monodelphis domestica	Gray short-tailed opossum	162.6	XP_001367097	0.0	568	89	92
11	Chrysemys picta bellii	Painted turtle	296.0	XP_008175974	0.0	572	76	83
12	Alligator mississippiensis	American alligator	296.0	XP_006266384	0.0	582	75	82
13	Pelodiscus sinensis	Chinese softshell turtle	296.0	XP_006127325	0.0	569	73	81
14	Xenopus tropicalis	Western clawed frog	371.2	NP_001121523	0.0	580	64	74
15	Oncorhynchus mykiss	Rainbow trout	400.1	CDQ84878	0.0	581	64	75
16	Danio rerio	Zebrafish	400.1	XP_001339329	0.0	595	63	74
17	Oryzias latipes	Japanese rice fish	400.1	XP_004076807	0.0	609	62	70
18	Takifugu rubripes	Pufferfish	400.1	XP_003970822	0.0	618	61	71

Distant orthologs

No.	Species	Common Name	Date of Divergence (MYA)	Accession No.	E-value	Length (aa)	Identity (%)	Similarity (%)
1	Nipponia Nippon	Crested ibis	296.0	XP_009472339	0.0	503	80	88
2	Charadrius vociferous	Killdeer	296.0	XP_009892747	0.0	456	82	90
3	Pseudopodoces humilis	Ground tit	296.0	XP_005533426	0.0	600	66	76
4	Latimeria chalumnae	West Indian Ocean coelacanth	414.9	XP_006011612	3E-177	429	65	75
5	Branchiostoma floridae	Florida lancelet	713.2	XP_002592972	9E-67	557	32	46
6	Strongylocentrotus purpuratus	Purple sea urchin	742.9	XP_003727419	3E-46	725	35	51
7	Aplysia californica	California sea slug	782.7	XP_005113015	4E-21	692	25	39
8	Nematostella vectensis	Starlet sea anemone	855.3	XP_001632706	4E-19	494	24	39
9	Trichoplax adhaerens	-	-	XP_002108809	5E-15	645	24	41

Post-translational modifications

C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546. All three sites are relatively well-conserved throughout mammals, reptiles, birds, amphibians, and bony fishes. The protein has no predicted N-myristoylation, as it has no N-terminal glycine. However, C7orf43 is predicted to have one N-acetylation on a serine residue at the N-terminus.

Secondary structure

The secondary structure of C7orf43 is yet to be determined. However, C7orf43 is predicted to have no transmembrane domain and to eventually be secreted from the cell. An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs. Similarly conserved alpha helix motifs have been predicted, one near the N-terminus and one near the C-terminus.

Clinical significance

While no studies have focused on the characterization of C7orf43, several large-scale screenings have revealed information related to C7orf43 function. A study using FLAG affinity purification mass spectrometry (AP-MS) to profile protein interactions in the Hippo signaling pathway identified C7orf43 as one of the interacting proteins. C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling. AMOTL2 is also known to be an inhibitor of Wnt signaling, a pathway with known associations to cancer development, and to be a factor for angiogenesis, a process essential to tumour maintenance and metastasis.

Several studies have linked C7orf43 to carcinomic events. Other studies have also linked C7orf43 to carcinomic events. A large-scale yeast two-hybrid experiment identified C7orf43 to be interacting with transmembrane protein 50A (TMEM50A), also known as cervical cancer gene 9 or small membrane protein 1 (SMP1). While the exact function of TMEM50A is unknown, it has been associated with cervical cancer.

C7orf43 has also been identified as a target gene of the transcription factor AP-2 gamma (TFAP2C). TFAP2C has been shown to be involved in the development, differentiation, and oncogenesis of mammary tissues. Specifically, TFAP2C has a role in breast carcinoma through its regulatory effect to ESR1 and ERBB2, both of which are receptors whose aberrations have been associated with breast carcinomas. TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.

Through its location in the q arm of chromosome 7, C7orf43 has been linked to various diseases. Several diseases have been described as having deletions in the q arm of chromosome 7, among them are myeloid disorders, including acute myelogenous leukemia and myelodysplasia.

External links

• Human C7orf43 genome location and C7orf43 gene details page in the UCSC Genome Browser.

Further reading

• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, et al. (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.
• Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology". Science. 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.