CCHCR1 explained

Coiled-coil alpha-helical rod protein 1, also known as CCHCR1, is a protein which in humans is encoded by the CCHCR1 gene.^{[1] [2] [3]}

Gene

The Human CCHCR1 gene is located at 6p21.33. It is also known as Coiled-Coil Alphahelical Rod Protein 1, C6orf18, Putative Gene 8 Protein, SBP, HCR (A-Helix Coiled-Coil Rod Homologue), pg8, StAR-Binding Protein, and Pg8.

Homology

Homologes for CCHCR1 are conserved through tetrapods.

Orthologs

CCHCR1 has orthologs throughout vertebrates.

Phylogeny

Phylogenetic analysis with ClustalW indicated that CCHCR1

The CCHCR1 gene has

Protein

Structure

The structure of CCHCR1 is primarily composed of alpha-helices, coils, and a small amount of beta sheets, according to PELE.^[4]

Function

May be a regulator of keratinocyte proliferation or differentiation.

Interacting Proteins

CCHCR1 has been shown to interact with POLR2C,^[5] KRT17,^[6] TOP3B,^[7] Steroidogenic acute regulatory protein,^[6] TRAF4,^[8] HLA-C,^[9] TCF19,^[9] SNX29,^[10] EEF1D,^[11] and EEF1B2.^[11]

Clinical significance

In genetically engineered mice, certain CCHCR1 polymorphisms cause upregulation of the expression of cytokeratins 6 (KRT6A), 16 (KRT16) and 17 (KRT17) and change in expression in other genes associated with terminal differentiation and formation of the cornified cell envelope. These CCHCR1 polymorphisms may therefore be associated with a susceptibility to psoriasis.^[12] Defective functioning of CCHCR1 may lead to abnormal keratinocyte proliferation which is a key feature of psoriasis.^[13]

CCHCR1 polymorphisms have also been found to be associated with multiple sclerosis.^[14]

See also

• Coiled coil

Further reading

• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O . Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence . Nature . 377 . 6547 Suppl . 3–174 . 1995 . 7566098 . .
• Oka A, Tamiya G, Tomizawa M, Ota M, Katsuyama Y, Makino S, Shiina T, Yoshitome M, Iizuka M, Sasao Y, Iwashita K, Kawakubo Y, Sugai J, Ozawa A, Ohkido M, Kimura M, Bahram S, Inoko H . Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene . Hum. Mol. Genet. . 8 . 12 . 2165–70 . 1999 . 10545595 . 10.1093/hmg/8.12.2165 . free .
• Asumalahti K, Laitinen T, Itkonen-Vatjus R, Lokki ML, Suomela S, Snellman E, Saarialho-Kere U, Kere J . A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele . Hum. Mol. Genet. . 9 . 10 . 1533–42 . 2000 . 10888604 . 10.1093/hmg/9.10.1533 . free .
• O'Brien KP, Holm SJ, Nilsson S, Carlén L, Rosenmüller T, Enerbäck C, Inerot A, Ståhle-Bäckdahl M . The HCR gene on 6p21 is unlikely to be a psoriasis susceptibility gene . J. Invest. Dermatol. . 116 . 5 . 750–4 . 2001 . 11348465 . 10.1046/j.0022-202x.2001.01323.x . free .
• Asumalahti K, Veal C, Laitinen T, Suomela S, Allen M, Elomaa O, Moser M, de Cid R, Ripatti S, Vorechovsky I, Marcusson JA, Nakagawa H, Lazaro C, Estivill X, Capon F, Novelli G, Saarialho-Kere U, Barker J, Trembath R, Kere J . Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus . Hum. Mol. Genet. . 11 . 5 . 589–97 . 2002 . 11875053 . 10.1093/hmg/11.5.589 . free .
• Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS . Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase . J. Biol. Chem. . 277 . 31 . 28051–7 . 2002 . 12023963 . 10.1074/jbc.M202665200 . free .
• Sugawara T, Shimizu H, Hoshi N, Nakajima A, Fujimoto S . Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system . J. Biol. Chem. . 278 . 43 . 42487–94 . 2003 . 12909641 . 10.1074/jbc.M302291200 . free .
• Suomela S, Elomaa O, Asumalahti K, Kariniemi AL, Karvonen SL, Peltonen J, Kere J, Saarialho-Kere U . HCR, a candidate gene for psoriasis, is expressed differently in psoriasis and other hyperproliferative skin disorders and is downregulated by interferon-gamma in keratinocytes . J. Invest. Dermatol. . 121 . 6 . 1360–4 . 2003 . 14675183 . 10.1046/j.1523-1747.2003.12642.x . free .
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nat. Biotechnol. . 22 . 6 . 707–16 . 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM . miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1 . RNA Biol . 1 . 2 . 106–13 . 2004 . 17179747 . 10.4161/rna.1.2.1066 . free .
• Tiala I, Suomela S, Huuhtanen J, Wakkinen J, Hölttä-Vuori M, Kainu K, Ranta S, Turpeinen U, Hämäläinen E, Jiao H, Karvonen SL, Ikonen E, Kere J, Saarialho-Kere U, Elomaa O . The CCHCR1 (HCR) gene is relevant for skin steroidogenesis and downregulated in cultured psoriatic keratinocytes . J. Mol. Med. . 85 . 6 . 589–601 . 2007 . 17221218 . 10.1007/s00109-006-0155-0 . 25864002 .
• Suomela S, Kainu K, Onkamo P, Tiala I, Himberg J, Koskinen L, Snellman E, Karvonen SL, Karvonen J, Uurasmaa T, Reunala T, Kivikäs K, Jansén CT, Holopainen P, Elomaa O, Kere J, Saarialho-Kere U . Clinical associations of the risk alleles of HLA-Cw6 and CCHCR1*WWCC in psoriasis . Acta Derm. Venereol. . 87 . 2 . 127–34 . 2007 . 17340018 . 10.2340/00015555-0184 . free .
• Elomaa O, Majuri I, Suomela S, Asumalahti K, Jiao H, Mirzaei Z, Rozell B, Dahlman-Wright K, Pispa J, Kere J, Saarialho-Kere U . Transgenic mouse models support HCR as an effector gene in the PSORS1 locus . Human Molecular Genetics . 13 . 15 . 1551–61 . Aug 2004 . 15190014 . 10.1093/hmg/ddh178 . free .

Notes and References

1. Web site: Entrez Gene: CCHCR1 coiled-coil alpha-helical rod protein 1.
2. Asumalahti K, Laitinen T, Itkonen-Vatjus R, Lokki ML, Suomela S, Snellman E, Saarialho-Kere U, Kere J . A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele . Hum. Mol. Genet. . 9 . 10 . 1533–42 . June 2000 . 10888604 . 10.1093/hmg/9.10.1533 . free .
3. Oka A, Tamiya G, Tomizawa M, Ota M, Katsuyama Y, Makino S, Shiina T, Yoshitome M, Iizuka M, Sasao Y, Iwashita K, Kawakubo Y, Sugai J, Ozawa A, Ohkido M, Kimura M, Bahram S, Inoko H . Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene . Hum. Mol. Genet. . 8 . 12 . 2165–70 . November 1999 . 10545595 . 10.1093/hmg/8.12.2165 . free .
4. 10.1016/S0098-3004(98)00117-4 . 0098-3004 . 25 . 2 . 201–203. Boudreau. A. E.. PELE—a version of the MELTS software program for the PC platform . Comput. Geosci.. Mar 1999 . 1999CG.....25..201B.
5. Corbi N, Bruno T, De Angelis R, Di Padova M, Libri V, Di Certo MG, Spinardi L, Floridi A, Fanciulli M, Passananti C . RNA polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product . J. Cell Sci. . 118 . Pt 18 . 4253–60 . September 2005 . 16141233 . 10.1242/jcs.02545 . free .
6. Tervaniemi MH, Siitonen HA, Söderhäll C, Minhas G, Vuola J, Tiala I, Sormunen R, Samuelsson L, Suomela S, Kere J, Elomaa O . Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization . PLOS ONE . 7 . 11 . e49920 . 2012 . 23189171 . 10.1371/journal.pone.0049920 . 3506594. 2012PLoSO...749920T . free .
7. Nicholas TJ, Baker C, Eichler EE, Akey JM . A high-resolution integrated map of copy number polymorphisms within and between breeds of the modern domesticated dog . BMC Genomics . 12 . 414 . 16 August 2011 . 21846351 . 10.1186/1471-2164-12-414 . 3166287 . free .
8. Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS . Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase . The Journal of Biological Chemistry . 277 . 31 . 28051–7 . Aug 2002 . 12023963 . 10.1074/jbc.M202665200 . free .
9. Petersdorf EW, Malkki M, Gooley TA, Spellman SR, Haagenson MD, Horowitz MM, Wang T . MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation . Science Translational Medicine . 4 . 144 . 144ra101 . Jul 2012 . 22837536 . 10.1126/scitranslmed.3003974 . 3633562.
10. Yang HH, Hu N, Wang C, Ding T, Dunn BK, Goldstein AM, Taylor PR, Lee MP . Influence of genetic background and tissue types on global DNA methylation patterns . PLOS ONE . 5 . 2 . e9355 . 23 February 2010 . 20186319 . 10.1371/journal.pone.0009355 . 2826396. 2010PLoSO...5.9355Y . free .
11. Corbi N, Batassa EM, Pisani C, Onori A, Di Certo MG, Strimpakos G, Fanciulli M, Mattei E, Passananti C . The eEF1γ subunit contacts RNA polymerase II and binds vimentin promoter region . PLOS ONE . 5 . 12 . e14481 . 31 December 2010 . 21217813 . 10.1371/journal.pone.0014481 . 3013090. 2010PLoSO...514481C . free .
12. Elomaa O, Majuri I, Suomela S, Asumalahti K, Jiao H, Mirzaei Z, Rozell B, Dahlman-Wright K, Pispa J, Kere J, Saarialho-Kere U . Transgenic mouse models support HCR as an effector gene in the PSORS1 locus . Hum. Mol. Genet. . 13 . 15 . 1551–61 . August 2004 . 15190014 . 10.1093/hmg/ddh178 . free .
13. Tiala I, Wakkinen J, Suomela S, Puolakkainen P, Tammi R, Forsberg S, Rollman O, Kainu K, Rozell B, Kere J, Saarialho-Kere U, Elomaa O . The PSORS1 locus gene CCHCR1 affects keratinocyte proliferation in transgenic mice . Hum. Mol. Genet. . 17 . 7 . 1043–51 . April 2008 . 18174193 . 10.1093/hmg/ddm377 . free .
14. Lin X, Deng FY, Lu X, Lei SF . Susceptibility Genes for Multiple Sclerosis Identified in a Gene-Based Genome-Wide Association Study . Journal of Clinical Neurology . 11 . 4 . 311–8 . 2015 . 26320842 . 4596110 . 10.3988/jcn.2015.11.4.311 .