C3orf62

Chromosome 3 Open Reading Frame 62 (C3orf62), is a protein that in humans is encoded by the C3orf62 gene. C3orf62 is a glycine depleted protein relative to the amount of glycine in proteins in the rest of the genome.[1] C3orf62 has a KKXX-like motif and is predicted to be localized in the nucleus.[2] Expression of C3orf62 remains highest in whole blood.[3]

C3orf62
Identifiers
Symbol	C3orf62
Alt. names	CC062, FLJ43654
NCBI gene	375341
HGNC	24771
RefSeq	NM_198562.21
UniProt	Q6ZUJ4
Other data
Locus	Chr. 3 p21.31{{{LocusSupplementaryData}}}

Gene

Locus

C3orf62 is mapped to the reverse strand of chromosome 3 at 3p21.31 and spans 9.313 bases.[4] C3orf62 starts at 49,268,597 base pairs from the terminus of the short arm (pter) and ending at 49,277,909 base pairs pter. This gene is known to have 3 exons, 4 transcripts, and 37 orthologues.[5][3][6][7][8]

Gene neighborhood

C3orf62 is flanked by Ubiquitin Specific Protease 4 (USP4) and Coil-Coiled Domain Containing 36 (CCDC36).

C3orf62 and its gene neighbors on chromosome 3 from NCBI

Aliases

C3orf62 possesses the following alternate names and synonyms: CC062; FLJ43654.[6][9]

Protein

Primary sequence

C3orf62 human protein (Q6ZUJ4) is 267 amino acids long, and has a molecular mass of 30,194 Daltons.[5] The isoelectric point of C3orf62 is roughly 5.2. The unmodified C3orf62 protein is a “glycine depleted protein” relative to amounts of glycine in proteins in the rest of the genome.[1] It appears that glycine is evenly distributed throughout the C3orf62 sequence with no preference of areas to cluster in. Before post-translational modifications, C3orf62 is an acidic protein. No charge clusters are present in C3orf62, and no specific spacing of cysteine is found. The isoelectric point of C3orf62 is 5.211000.[10]

Name	Ensembl Transcript ID[7][3]	Base Pairs	Protein	Biotype	CCDS	Uniprot	Refseq
C3orf62-001	ENST00000343010.7	4235	267aa	Protein encoding	CCDS2792	Q6ZUJ4	NM_198562, NP_940964
C3orf62-004	ENST00000436325.1	581	190aa	Protein encoding	-	C9JW57	-
C3orf62-003	ENST00000424960.1	602	98aa	Nonsense mediated decay	-	H7BZX3	-
C3orf62-002	ENST00000479673.1	3330	No protein	Retained intron	-	-	-

Domains and motifs

There are no known transmembrane domains for C3orf62.[9] C3orf62 has a KKXX-like motif in the C-terminus meaning C3orf62 may be responsible for retrieval of endoplasmic reticulum (ER) membrane proteins from the Golgi apparatus.[11]

Secondary structure

Roughly 7 alpha helices are predicted for C3orf62 through Pele Protein Structure Protein Prediction and strengthened through orthologous secondary structure predictions by Ali2D.[9][12]

Subcellular localization

C3orf62 is predicted to be localized in the nucleus.[2] The k-nearest neighbors algorithm predicts C3orf62 to be classified as follows: k=9/23; 69.6% nuclear, 13.0% mitochondrial, 13.0% cytoskeletal, 4.3% cytoplasmic.[2]

Expression

C3orf62 is expressed in more than 30 different tissues; highest expression is in whole blood.[6][3][5] Specifically, highest expression of C3orf62 is in the following tissues: lung, tonsil, trachea, small intestine, mammary gland, and salivary gland. Through analysis of various microarray studies, C3orf62 is found to have consistently high expression compared to other genes tested in the datasets.[13] C3orf62 has low expression in brain tissues.

Diagram depicting the expression of C3orf62 in tissues throughout the body

Post-transcriptional modifications

C3orf62 possess two post-translational modifications, both are phosphorylation sites with locations at amino acid 210 and 224.[5] A natural variant is found at amino acid 110 (Glutamic acid (E)--> Lysine K).[8][7]

It appears as though C3orf62 may have a YinOYang site at residue 115, meaning that this Threonine residue is predicted to be O-GlycNAcylated as well as phosphorylated. This site may be reversibly and dynamically modified by O-GlcNAc or Phosphate groups at different times in the cell.[14]

Regulation of expression

Thirteen promoters have been predicted for C3orf62.[15]

Transcript variants

Transcription of C3orf62 produces 5 alternatively spliced variants and 1 unspliced form. Of the four splice variants, two of them are protein coding, one is nonsense meditated decay, and one is a retained intron.[6] QIAGEN denotes the following as transcription factor binding sites in the C3orf62 promoter: TFCP2, Pax-6, p53, MyoD, YY1, Ik-2, AREB6, IRF-7A3.[3]

Function

Function of C3orf62 is not currently understood by the scientific community.

Interactions

Upwards of 12 interacting proteins have been predicted for C3orf62.[16][17][18] Interacting proteins with the strongest confidence to interact with C3orf62 include: HAUS augmin-like complex subunit 1 (HAUS-1), Inhibitor of growth protein 5 (ING5), Thioredoxin domain-containing protein 9 (TXNDC9), and MORF4-family associated proteins (MORF4L1, MFRAP1).

Chemicals known to interact with C3orf62 include the following: Aflatoxin B1, Hydralazine, Valproic acid, and Decitabine.[6]

Clinical significance

Interstitial deletions of chromosome 3 are rare, and only a few patients with a microdeletion of 3p21.31 have been reported to date. Characteristic clinical features found in patients with a microdeletion of 3p21.31 include developmental delay and distinctive facial features (including arched eyebrows, hypertelorism, epicanthus, and micrognathia).[19][20][21]

In the gene region, NCBI SNP identified 1,326 SNPS on the reverse minus strand of C3orf62.[22] In the coding region, NCBI SNP identified 147 common SNPs.

Homology

Paralogs

There are no known paralogs of C3orf62.[23]

Orthologs

The ortholog space of C3orf62 is fairly narrow, with the majority of orthologs found in mammals.[23] A small fraction of orthologs have also been found in the following classes: Reptila, Sarcopterygii, and Actinoptergii.

The groupings of nearly all Mammalia ortholog sequences of C3orf62 are as follows: E-value: 2e-94 to 1e-169; similarity 56-84%. Mammals in this group consist largely of primates but also include the following orders: Perissodactyla, Rodentia, Carnivora, Proboscidea, Cetartiodactyla, Cingulata, Artiodactyla, Eulipotyphla, Diselphimorphia, and Afrosoricida.[23]

More distantly related ortholog sequences of C3orf62 include organisms from classes Reptilia, Sarcopterygii, and Actinopterygii ranging from an E-value of 8e-10 to 3e-59 with similarity of 24-39%.[23] Organisms in this grouping consist of Testudines, Coelacanthiformes, Squamata, and Osteoglossiformes orders. No ortholog sequences of C3orf62 were found for the following life forms: Bacteria, archaea, protist, plant, fungus, trichoplax, invertebrate, amphibian, or bird.

Genus and Species	Common Name	Class	Accession	Percent Identity
Homo sapiens	Human	Mammalia	NP_940964	100
Microcebus murinus	Grey Mouse Lemur	Mammalia	XP_012626718	88
Propithecus coquereli	Coquerel's sifaka (lemur)	Mammalia	XP_012510880	86.9
Equus caballus	Horse	Mammalia	NP_001295877	84.3
Loxodonta Africana	African elephant	Mammalia	XP_003409711	83.2
Castor Canadensis	North American Beaver	Mammalia	XP_020037316	81.6
Otolemur garnettii	Garnett's Greater Galago	Mammalia	XP_003800633	81.6
Camelus bactrianus	Bactrian camel	Mammalia	XP_010967491.1	78.3
Ailuropoda melanoleuca	Giant Panda	Mammalia	XP_019656626	77.7
Canis lupus familiaris	Dog	Mammalia	XP_003432924	77.2
Vicugna pacos	Alpaca	Mammalia	XP_006196356	77.2
Condylura cristata	Star-nosed mole	Mammalia	XP_012575760	76.8
Felis catus	Cat	Mammalia	XP_003982269	75.1
Pteropus vampyrus	Large flying fox	Mammalia	XP_011373720	73.3
Pantholops hodgsonii	Tibetan antelope	Mammalia	XP_005969318	72.6
Ictidomys tridecemlineatus	Thirteen lines ground squirrel	Mammalia	XP_005326967	71
Sorex araneus	Common Shrew	Mammalia	XP_012789682	69.5
Monodelphis domestica	Gray short-tailed opossum	Mammalia	XP_001367907	65.4
Echinops telfairi	Lesser Hedgehog Tenrec	Mammalia	XP_004715283	63.7
Orcinus orca	Killer whale	Mammalia	XP_004283985	61.2
Dasypus novemcinctus	Nine banded armadillo	Mammalia	XP_004451950	58.2
Dipodomys ordii	Ord's Kangaroo Rat	Mammalia	XP_012883511	56.3
Myotis lucifugus	Little Brown Myotis	Mammalia	XP_006107033	39.3
Pelodiscus sinensis	Chinese softshell turtle	Reptillia	XP_014426235	38.5
Chelonia mydas	Green Sea Turtle	Reptillia	XP_007061837	37.1
Latimeria chalumnae	West Indian Ocean coelacanth (fish)	Sarcopterygii	XP_005992740	35.3
Anolis carolinensis	Green anole (lizard)	Reptillia	XP_008103227	33.1
Gekko japonicus	Japanese Gecko	Reptillia	XP_015262861	30.1

Phylogeny

The most distant ortholog of C3orf62 are species of fish and amphibians. Orthologs of C3orf62 are not seen in birds, invertebrates, or bacteria.[23]

References

1. "SAPS". SDSC Biology Workbench. Retrieved 23 April 2017.
2. "C3orf62 Homo sapiens". PSORT WWW Server.
3. "Homo sapiens C3orf62". GeneCards. Retrieved 5 February 2017.
4. "Homo sapiens C3orf62". NCBI Nucleotide. Retrieved 5 February 2017.
5. "Homo sapiens C3orf62". NCBI Gene. Retrieved 5 February 2017.
6. "Humans 2010-C3orf62". Aceview. Retrieved 5 February 2017.
7. "C3orf62". UniProtKB.
8. "C3orf62". Ensembl. Retrieved 5 February 2017.
9. "Human Gene C3orf62". UCSC. Retrieved 5 February 2017.
10. "PI". SDSC Biology Workbench.
11. "C3orf62". PSORT WWW Server. Retrieved 7 May 2017.
12. "C3orf62". Ali2D. Archived from the original on 22 December 2016. Retrieved 7 May 2017.
13. "C3orf62 GEO Profiles". NCBI GEO. Retrieved 24 April 2017.
14. "C3orf62". YingOYang. Retrieved 7 May 2017.
15. "C3orf62". Genomatix. Retrieved 7 May 2017.
16. "C3orf62". STRING Interaction Network. Retrieved 7 May 2017.
17. "C3orf62". BioGRID. Retrieved 7 May 2017.
18. "C3orf62". InAct. Retrieved 7 May 2017.
19. Haldeman-Englert CR, Gai X, Perin JC, Ciano M, Halbach SS, Geiger EA, McDonald-McGinn DM, Hakonarson H, Zackai EH, Shaikh TH (13 Dec 2008). "A 3.1-Mb microdeletion of 3p21.31 associated with cortical blindness, cleft lip, CNS abnormalities, and developmental delay". European Journal of Medical Genetics. 52 (4): 265–8. doi:10.1016/j.ejmg.2008.11.005. PMC 4391973. PMID 19100872.
20. Eto K, Sakai N, Shimada S, Shioda M, Ishigaki K, Hamada Y, Shinpo M, Azuma J, Tominaga K, Shimojima K, Ozono K, Osawa M, Yamamoto T (December 2013). "Microdeletions of 3p21.31 characterized by developmental delay, distinctive features, elevated serum creatine kinase levels, and white matter involvement". American Journal of Medical Genetics. Part A. 161A (12): 3049–56. doi:10.1002/ajmg.a.36156. PMID 24039031.
21. Lovrecic L, Bertok S, Žerjav Tanšek M (May 2016). "A New Case of an Extremely Rare 3p21.31 Interstitial Deletion". Molecular Syndromology. 7 (2): 93–8. doi:10.1159/000445227. PMC 4906427. PMID 27385966.
22. "C3orf62". NCBI SNP.
23. "C3orf62". NCBI BLAST. Retrieved 7 May 2017.