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C15orf62
Identifiers
Aliases	C15orf62, chromosome 15 open reading frame 62
External IDs	MGI: 3651144; HomoloGene: 85847; GeneCards: C15orf62; OMA:C15orf62 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) Band 15q15.1 Start 40,769,980 bp End 40,772,449 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2|2 E5 Start 119,004,990 bp End 119,008,056 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell skin of leg oral cavity amniotic fluid tendon of biceps brachii skin of abdomen olfactory zone of nasal mucosa minor salivary glands mucosa of pharynx granulocyte Top expressed in lip esophagus skin of abdomen hair follicle skin of back superior cervical ganglion cornea conjunctival fornix skin of external ear embryo More reference expression data BioGPS n/a
Gene ontology Molecular function GTPase activator activity Cellular component cytoplasm plasma membrane mitochondrion Biological process positive regulation of pseudopodium assembly positive regulation of actin filament polymerization Rho protein signal transduction regulation of cell shape positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 643338 623781 Ensembl ENSG00000188277 ENSMUSG00000055926 UniProt A8K5M9 Q8CE97 RefSeq (mRNA) NM_001130448 NM_001039223 RefSeq (protein) NP_001123920 NP_001034312 Location (UCSC) Chr 15: 40.77 – 40.77 Mb Chr 2: 119 – 119.01 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

C15orf62 is a protein which in humans is encoded by the C15orf62 gene. The protein displays high levels of expression in the esophagus and skin of human tissue. C15orf62 is a regulatory protein involved in mitochondrial function and cytoskeletal organization, playing roles in ribosomal biogenesis, Rho protein signal transduction, and protein turnover through ubiquitination. It connects mitochondrial activity to cell structure, signaling, and biogenesis through its unique amino acid composition and post-translational modifications.

Gene

The gene is also known as chromosome 15 open reading frame 62. The human C15orf62 gene spans 2,470 base pairs, and is oriented on the plus strand of cytogenetic band 15q15.1. The C15orf62 gene contains a single exon and transcribes a protein-coding mRNA that encodes a 175 amino acid protein.

Protein

Human C15orf62 encodes a single protein, with just a singular isoform. The protein has a molecular weight of 19.7 kD and an isoelectric point (pI) of 8.66. C15orf62 has a high abundance of arginine and significantly lower levels of valine. The protein has one prominent amino acid repeat, "RL-R-SS."

The protein contains eight motifs; an amidation site, an N-glycosylation site, cAMP- and a cGMP-dependent protein kinase phosphorylation sites, a casein kinase II phosphorylation site, an N-myristoylation site, a protein kinase C phosphorylation site, and a protein prenyltransferases alpha subunit repeat profile, and a domain of unknown function (DUF2437).

C15orf62 contains a histidine kinase sensor, TorS sensor domain, functioning in response to diverse signals and mediating signal transduction across the plasma membrane in all prokaryotes and certain eukaryotes.

Gene Level Regulation

C15orf62 RNA expression patterns reveal tissue enhanced in the esophagus and skin. Ubiquitously moderate to low expression can be seen across other human tissues. Microarray data from normal tissue expression profiling of 24 human C15orf62 tissue samples revealed expression is moderate to low in most parts of the body based on findings in NCBIGeo. In-situ hybridization of the human brain from Allen Brain Atlas indicated that C15orf62 exhibits the highest expression levels throughout the myelencephalon. In contrast, expression in the cerebral cortex is exceptionally lower.

immunohistochemical staining of the human esophagus displayed moderate cytoplasmic positivity of C15orf62 in squamous epithelia cells.

Transcript Level Regulation

The gene contains an active enhancer region proceeding the coding sequence (CDS) and three histone H3 lysine 4 mono-methylation (H3K4me1) human embryonic stem cell (hESC) sites marking poised or active enhancers throughout C15orf62. H3K4me1 facilitates promoter-enhancer interactions and gene activation during embryonic stem cell differentiation.

Protein Level Regulation

The C15orf62 gene is localized in the mitochondria based on a 78.3% confidence.

The following post-translation modification tools revealed; YinoYang indicated several O-beta GlcNAc attachment signals. Phosphosite detected six phosphorylation sites. NetPhos - 3.1 indicated several phosphorylation sites. NetAcet - 1.0 displayed an acetylation at one sequence, position 3 T, and NetNGlyc predicted one signal at position 11, NASF.

PSORT II detected two nuclear localization signals highly conserved in orthologs (RPRR and PRRLRRQ).

PSORT II identified a cleavage site for a mitochondrial pre-sequence in the protein, using the Gavel tool. The cleavage occurs after residue 38, at the sequence RRQ|SS. This is consistent with the R-2 motif (arginine at position -2), which is a common feature of mitochondrial targeting sequences cleaved by mitochondrial processing peptidases. This suggests that the protein is transported to the mitochondria, where its pre-sequence is removed to generate the mature form.

Homology

Orthologs

The C15orf62 gene has many orthologs but is only found in vertebrates. The most divergent species studied so far are within the class Chondrichthyes (cartilaginous fish), such as the horn shark (Heterodontus francisci), which diverged approximately 462 million years ago (MYA).

The gene is present across mammals, birds, reptiles, and amphibians, though its sequence similarity and identity to the human ortholog vary significantly. For example, reptiles such as the Pinta Island tortoise (Chelonoidis abingdonii) and the loggerhead sea turtle (Caretta caretta) exhibit around 40% sequence identity and over 60% similarity. However, amphibians like the tiny Cayenne caecilian (Microcaecilia unicolor) and the two-lined caecilian (Rhinatrema bivittatum) have even more divergent sequences, with identity dropping as low as 26-28%.

This pattern suggests that while C15orf62 is well-conserved within the vertebrate lineage, its function may have diverged or adapted significantly across different classes, especially in more evolutionarily distant groups such as amphibians and sharks.

The above table displays orthologs of human C15orf62 in organisms of various classes. The orthologs have been grouped according to the sequence identity of the human protein. Mammalia (100%), aves (38%-42%), reptilia (34%-41%), amphibia (26%-29%), and chondrichthyes (20%-23%). NCBI’s Blast, TimeTree, and EMBOSS Needle were utilized to collect the above data.

Paralogs

C15orf62 has no paralogs as can be determined by a BLAST run on NCBI Protein using the human C15orf62 sequence against the non-redundant database. The lack of significant results indicated that the gene has no duplications within the species.

Biochemistry

C15orf62 plays a key role in both mitochondrial function and cytoskeletal organization. It is involved in Rho protein signal transduction, regulating cytoskeletal dynamics and cell shape through interactions with small GTPases. In the mitochondria, it is directly involved in ribosomal biogenesis, supported by its interactions with mitochondrial ribosomal proteins such as MRPS18A and GFM2. The protein contains a mitochondrial targeting sequence that is cleaved at residue 38, confirming its role in mitochondrial processes. Additionally, C15orf62 interacts with NEDD4, an E3 ubiquitin ligase, indicating its involvement in protein turnover through ubiquitination. With its unique amino acid composition and multiple post-translational modification sites, C15orf62 acts as a regulatory protein connecting mitochondrial activity to processes like biogenesis, signaling, and cell structure.

Interacting Proteins

Human neural precursor cell expressed, developmentally down-regulated 4 (NEDD4), an E3 ubiquitin-protein ligase involved in regulating various cellular processes such as signal transduction, cell differentiation, and apoptosis, interacts with human C15orf62, as determined by phage display. This interaction suggests a role for C15orf62 in protein turnover through ubiquitination.

Additionally, C15orf62 has an interactome involving several mitochondrial proteins, including C15orf61, C3orf33, MRPS18A, MRPL53, GFM2, MTER4, and DNAJC11, indicating its involvement in mitochondrial ribosome biogenesis and other mitochondrial functions. Interactions with proteins like DNAJC17, DNAJC4, and ZFYVE19, localized in other cellular compartments, suggest C15orf62 may also be involved in processes beyond the mitochondria, such as protein folding and cell division.

Clinical Significance

C15orf62 has been identified as a methylene-driven gene in thyroid cancer. Hypomethylation causes gene over-expression, and hypermethylation leads to low gene expression, both key factors in tumor development. C15orf62 has also been linked to breast cancer susceptibility performing a role in mitochondrial ribosomal biogenesis, assembling mitochondrial ribosomes.

An expression profile for diabetes ORFs was detected in C15orf62 found in liver secretion. This indicates the capability of enhancing diagnostic markers for diabetes types 1 and 2. A distinct expression profile for C15orf62 was detected in in blood.

Identified single nucleotide polymorphisms (SNPs) include T75N, P83A, and S148fs.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000188277 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000055926 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "C15orf62 chromosome 15 open reading frame 62 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-09-20.
6. Moore, Jason O.; Hendrickson, Wayne A. (2009-09-09). "Structural Analysis of Sensor Domains from the TMAO-Responsive Histidine Kinase Receptor TorS". Structure. 17 (9): 1195–1204. doi:10.1016/j.str.2009.07.015. ISSN 0969-2126.
7. Kubo, Naoki; Chen, Poshen B.; Hu, Rong; Ye, Zhen; Sasaki, Hiroyuki; Ren, Bing (2024-05-02). "H3K4me1 facilitates promoter-enhancer interactions and gene activation during embryonic stem cell differentiation". Molecular Cell. 84 (9): 1742–1752.e5. doi:10.1016/j.molcel.2024.02.030. ISSN 1097-2765. PMC 11069443. PMID 38513661.{{cite journal}}: CS1 maint: PMC format (link)
8. "PSORT II Prediction". psort.hgc.jp. Retrieved 2024-12-05.
9. Chen, Zhiwei; Liu, Xiaoli; Liu, Fangfang; Zhang, Guolie; Tu, Haijian; Lin, Wei; Lin, Haifeng (2021-08-29). "Identification of 4-methylation driven genes based prognostic signature in thyroid cancer: an integrative analysis based on the methylmix algorithm". Aging (Albany NY). 13 (16): 20164–20178. doi:10.18632/aging.203338. ISSN 1945-4589. PMC 8436924. PMID 34456184.
10. Podder, Bristy Rani; Kheya, Ilora Shabnam; Elias, Sabrina Moriom (2024-02-01). "Breast cancer risk SNPs and associated expression QTLs focusing Bangladeshi population: An in silico analysis". Human Gene. 39: 201270. doi:10.1016/j.humgen.2024.201270. ISSN 2773-0441.
11. Narayanan, Ramaswamy (2014-07-19). ""Diabetes Associated Genes from the Dark Matter of the Human Proteome"". MOJ Proteomics & Bioinformatics. 1 (4). doi:10.15406/mojpb.2014.01.00020. ISSN 2374-6920. Archived from the original on 2024-07-15.

Suggested Reading

• Genes on human chromosome 15