ID CRGC_HUMAN Reviewed; 174 AA. AC P07315; Q53R50; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 24-JAN-2024, entry version 206. DE RecName: Full=Gamma-crystallin C; DE AltName: Full=Gamma-C-crystallin; DE AltName: Full=Gamma-crystallin 2-1; DE AltName: Full=Gamma-crystallin 3; GN Name=CRYGC; Synonyms=CRYG3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=4065573; DOI=10.1016/0378-1119(85)90218-5; RA den Dunnen J.T., Moormann R.J.M., Cremers F.P.M., Schoenmakers J.G.G.; RT "Two human gamma-crystallin genes are linked and riddled with Alu- RT repeats."; RL Gene 38:197-204(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=4033658; DOI=10.1128/mcb.5.6.1408-1414.1985; RA Meakin S.O., Breitman M.L., Tsui L.-C.; RT "Structural and evolutionary relationships among five members of the human RT gamma-crystallin gene family."; RL Mol. Cell. Biol. 5:1408-1414(1985). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2777080; DOI=10.1016/0378-1119(89)90223-0; RA den Dunnen J.T., van Neck J.W., Cremers F.P.M., Lubsen N.H., RA Schoenmakers J.G.G.; RT "Nucleotide sequence of the rat gamma-crystallin gene region and comparison RT with an orthologous human region."; RL Gene 78:201-213(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lens; RA Petrash J.M., Mathur S., Manoharan M., Andley U.P.; RT "Cloning and expression of human lens crystallins."; RL Invest. Ophthalmol. Vis. Sci. 36:S882-S882(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 2-26. RX PubMed=8999933; DOI=10.1074/jbc.272.4.2268; RA Lampi K.J., Ma Z., Shih M., Shearer T.R., Smith J.B., Smith D.L., RA David L.L.; RT "Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the RT identification of the major proteins in young human lens."; RL J. Biol. Chem. 272:2268-2275(1997). RN [9] RP METHYLATION AT CYS-23, AND MASS SPECTROMETRY. RX PubMed=12876325; DOI=10.1110/ps.0305403; RA Lapko V.N., Smith D.L., Smith J.B.; RT "Methylation and carbamylation of human gamma-crystallins."; RL Protein Sci. 12:1762-1774(2003). RN [10] RP INVOLVEMENT IN CTRCT2. RX PubMed=22876111; RA Guo Y., Su D., Li Q., Yang Z., Ma Z., Ma X., Zhu S.; RT "A nonsense mutation of CRYGC associated with autosomal dominant congenital RT nuclear cataracts and microcornea in a Chinese pedigree."; RL Mol. Vis. 18:1874-1880(2012). RN [11] RP 3D-STRUCTURE MODELING. RX PubMed=12507494; DOI=10.1016/s0006-291x(02)02895-4; RA Salim A., Zaidi Z.H.; RT "Homology models of human gamma-crystallins: structural study of the RT extensive charge network in gamma-crystallins."; RL Biochem. Biophys. Res. Commun. 300:624-630(2003). RN [12] RP VARIANT CTRCT2 PRO-5. RX PubMed=10521291; DOI=10.1086/302619; RA Heon E., Priston M., Schorderet D.F., Billingsley G.D., Girard P.O., RA Lubsen N., Munier F.L.; RT "The gamma-crystallins and human cataracts: a puzzle made clearer."; RL Am. J. Hum. Genet. 65:1261-1267(1999). RN [13] RP ERRATUM OF PUBMED:10521291. RA Heon E., Priston M., Schorderet D.F., Billingsley G.D., Girard P.O., RA Lubsen N., Munier F.L.; RL Am. J. Hum. Genet. 66:753-753(2000). RN [14] RP INVOLVEMENT IN CTRCT2. RX PubMed=10914683; DOI=10.1007/s004390000289; RA Ren Z., Li A., Shastry B.S., Padma T., Ayyagari R., Scott M.H., Parks M.M., RA Kaiser-Kupfer M.I., Hejtmancik J.F.; RT "A 5-base insertion in the gammaC-crystallin gene is associated with RT autosomal dominant variable zonular pulverulent cataract."; RL Hum. Genet. 106:531-537(2000). RN [15] RP VARIANT CTRCT2 TRP-168, AND VARIANT HIS-48. RX PubMed=12011157; DOI=10.1136/jmg.39.5.352; RA Santhiya S.T., Shyam Manohar M., Rawlley D., Vijayalakshmi P., RA Namperumalsamy P., Gopinath P.M., Loester J., Graw J.; RT "Novel mutations in the gamma-crystallin genes cause autosomal dominant RT congenital cataracts."; RL J. Med. Genet. 39:352-358(2002). RN [16] RP CHARACTERIZATION OF VARIANT CTRCT2 PRO-5. RX PubMed=12601044; DOI=10.1167/iovs.02-0950; RA Fu L., Liang J.J.-N.; RT "Alteration of protein-protein interactions of congenital cataract RT crystallin mutants."; RL Invest. Ophthalmol. Vis. Sci. 44:1155-1159(2003). RN [17] RP VARIANT CTRCT2 TRP-168. RX PubMed=18587492; RA Devi R.R., Yao W., Vijayalakshmi P., Sergeev Y.V., Sundaresan P., RA Hejtmancik J.F.; RT "Crystallin gene mutations in Indian families with inherited pediatric RT cataract."; RL Mol. Vis. 14:1157-1170(2008). RN [18] RP VARIANT HIS-48. RX PubMed=21423869; RA Kumar M., Agarwal T., Khokhar S., Kumar M., Kaur P., Roy T.S., Dada R.; RT "Mutation screening and genotype phenotype correlation of alpha-crystallin, RT gamma-crystallin and GJA8 gene in congenital cataract."; RL Mol. Vis. 17:693-707(2011). RN [19] RP VARIANT CTRCT2 CYS-129. RX PubMed=22052681; DOI=10.1002/humu.21648; RA Li X.Q., Cai H.C., Zhou S.Y., Yang J.H., Xi Y.B., Gao X.B., Zhao W.J., RA Li P., Zhao G.Y., Tong Y., Bao F.C., Ma Y., Wang S., Yan Y.B., Lu C.L., RA Ma X.; RT "A novel mutation impairing the tertiary structure and stability of gammaC- RT crystallin (CRYGC) leads to cataract formation in humans and zebrafish RT lens."; RL Hum. Mutat. 33:391-401(2012). RN [20] RP VARIANTS CTRCT2 HIS-48 AND 144-TYR--TYR-174 DEL. RX PubMed=29386872; RA Sun Z., Zhou Q., Li H., Yang L., Wu S., Sui R.; RT "Mutations in crystallin genes result in congenital cataract associated RT with other ocular abnormalities."; RL Mol. Vis. 23:977-986(2017). RN [21] RP VARIANT CTRCT2 PHE-78. RX PubMed=29914532; DOI=10.1186/s13023-018-0828-0; RA Li J., Leng Y., Han S., Yan L., Lu C., Luo Y., Zhang X., Cao L.; RT "Clinical and genetic characteristics of Chinese patients with familial or RT sporadic pediatric cataract."; RL Orphanet J. Rare Dis. 13:94-94(2018). RN [22] RP VARIANT CTRCT2 PRO-5. RX PubMed=33243271; DOI=10.1186/s13023-020-01613-3; RA Berry V., Ionides A., Pontikos N., Georgiou M., Yu J., Ocaka L.A., RA Moore A.T., Quinlan R.A., Michaelides M.; RT "The genetic landscape of crystallins in congenital cataract."; RL Orphanet J. Rare Dis. 15:333-333(2020). CC -!- FUNCTION: Crystallins are the dominant structural components of the CC vertebrate eye lens. CC -!- SUBUNIT: Monomer. {ECO:0000250}. CC -!- INTERACTION: CC P07315; P02489: CRYAA; NbExp=3; IntAct=EBI-6875941, EBI-6875961; CC P07315; P02511: CRYAB; NbExp=3; IntAct=EBI-6875941, EBI-739060; CC P07315; Q9C029: TRIM7; NbExp=3; IntAct=EBI-6875941, EBI-2813981; CC -!- DOMAIN: Has a two-domain beta-structure, folded into four very similar CC Greek key motifs. CC -!- MASS SPECTROMETRY: Mass=20747; Mass_error=0.2; Method=Electrospray; CC Evidence={ECO:0000269|PubMed:12876325}; CC -!- DISEASE: Cataract 2, multiple types (CTRCT2) [MIM:604307]: An CC opacification of the crystalline lens of the eye that frequently CC results in visual impairment or blindness. Opacities vary in CC morphology, are often confined to a portion of the lens, and may be CC static or progressive. CTRCT2 includes Coppock-like cataract, among CC others. Coppock-like cataract is a congenital pulverulent disk-like CC opacity involving the embryonic nucleus with many tiny white dots in CC the lamellar portion of the lens. It is usually bilateral and CC dominantly inherited. In some cases, CTRCT2 is associated with CC microcornea without any other systemic anomaly or dysmorphism. CC Microcornea is defined by a corneal diameter inferior to 10 mm in both CC meridians in an otherwise normal eye. {ECO:0000269|PubMed:10521291, CC ECO:0000269|PubMed:10914683, ECO:0000269|PubMed:12011157, CC ECO:0000269|PubMed:12601044, ECO:0000269|PubMed:18587492, CC ECO:0000269|PubMed:22052681, ECO:0000269|PubMed:22876111, CC ECO:0000269|PubMed:29386872, ECO:0000269|PubMed:29914532, CC ECO:0000269|PubMed:33243271}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the beta/gamma-crystallin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Eye disease Crystallin, gamma-C (CRYGC); Note=Leiden CC Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/CRYGC"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M11973; AAA52114.1; -; Genomic_DNA. DR EMBL; M11972; AAA52114.1; JOINED; Genomic_DNA. DR EMBL; K03004; AAA52111.1; -; Genomic_DNA. DR EMBL; K03003; AAA52111.1; JOINED; Genomic_DNA. DR EMBL; M19364; AAA52110.1; -; Genomic_DNA. DR EMBL; U66582; AAC50899.1; -; mRNA. DR EMBL; AC093698; AAY24042.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70433.1; -; Genomic_DNA. DR EMBL; BC074954; AAH74954.1; -; mRNA. DR EMBL; BC074955; AAH74955.1; -; mRNA. DR CCDS; CCDS2379.1; -. DR PIR; B24520; CYHUG2. DR RefSeq; NP_066269.1; NM_020989.3. DR RefSeq; XP_011508964.1; XM_011510662.1. DR PDB; 2NBR; NMR; -; A=2-174. DR PDBsum; 2NBR; -. DR AlphaFoldDB; P07315; -. DR SMR; P07315; -. DR BioGRID; 107810; 36. DR IntAct; P07315; 6. DR MINT; P07315; -. DR STRING; 9606.ENSP00000282141; -. DR ChEMBL; CHEMBL4296285; -. DR GlyGen; P07315; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P07315; -. DR PhosphoSitePlus; P07315; -. DR BioMuta; CRYGC; -. DR DMDM; 117464; -. DR MassIVE; P07315; -. DR PaxDb; 9606-ENSP00000282141; -. DR PeptideAtlas; P07315; -. DR ProteomicsDB; 51985; -. DR Antibodypedia; 34194; 204 antibodies from 27 providers. DR DNASU; 1420; -. DR Ensembl; ENST00000282141.4; ENSP00000282141.3; ENSG00000163254.5. DR Ensembl; ENST00000646204.2; ENSP00000496418.1; ENSG00000285011.2. DR GeneID; 1420; -. DR KEGG; hsa:1420; -. DR MANE-Select; ENST00000282141.4; ENSP00000282141.3; NM_020989.4; NP_066269.1. DR UCSC; uc002vco.4; human. DR AGR; HGNC:2410; -. DR CTD; 1420; -. DR DisGeNET; 1420; -. DR GeneCards; CRYGC; -. DR HGNC; HGNC:2410; CRYGC. DR HPA; ENSG00000163254; Tissue enriched (testis). DR MalaCards; CRYGC; -. DR MIM; 123680; gene. DR MIM; 604307; phenotype. DR neXtProt; NX_P07315; -. DR OpenTargets; ENSG00000163254; -. DR Orphanet; 1377; Cataract-microcornea syndrome. DR Orphanet; 441452; Early-onset lamellar cataract. DR Orphanet; 98991; Early-onset nuclear cataract. DR Orphanet; 98984; Pulverulent cataract. DR PharmGKB; PA26917; -. DR VEuPathDB; HostDB:ENSG00000163254; -. DR eggNOG; ENOG502RXJY; Eukaryota. DR GeneTree; ENSGT00940000159232; -. DR HOGENOM; CLU_081883_1_1_1; -. DR InParanoid; P07315; -. DR OMA; CYECTTD; -. DR OrthoDB; 3998747at2759; -. DR PhylomeDB; P07315; -. DR PathwayCommons; P07315; -. DR SignaLink; P07315; -. DR SIGNOR; P07315; -. DR BioGRID-ORCS; 1420; 18 hits in 1151 CRISPR screens. DR GeneWiki; CRYGC; -. DR GenomeRNAi; 1420; -. DR Pharos; P07315; Tbio. DR PRO; PR:P07315; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P07315; Protein. DR Bgee; ENSG00000163254; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 9 other cell types or tissues. DR ExpressionAtlas; P07315; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005212; F:structural constituent of eye lens; IBA:GO_Central. DR GO; GO:0002088; P:lens development in camera-type eye; IBA:GO_Central. DR GO; GO:0007601; P:visual perception; IMP:UniProtKB. DR Gene3D; 2.60.20.10; Crystallins; 2. DR InterPro; IPR001064; Beta/gamma_crystallin. DR InterPro; IPR011024; G_crystallin-like. DR PANTHER; PTHR11818; BETA/GAMMA CRYSTALLIN; 1. DR PANTHER; PTHR11818:SF32; GAMMA-CRYSTALLIN C; 1. DR Pfam; PF00030; Crystall; 2. DR PRINTS; PR01367; BGCRYSTALLIN. DR SMART; SM00247; XTALbg; 2. DR SUPFAM; SSF49695; gamma-Crystallin-like; 1. DR PROSITE; PS50915; CRYSTALLIN_BETA_GAMMA; 4. DR Genevisible; P07315; HS. PE 1: Evidence at protein level; KW 3D-structure; Cataract; Direct protein sequencing; Disease variant; KW Eye lens protein; Methylation; Reference proteome; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:8999933" FT CHAIN 2..174 FT /note="Gamma-crystallin C" FT /id="PRO_0000057587" FT DOMAIN 2..40 FT /note="Beta/gamma crystallin 'Greek key' 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028" FT DOMAIN 41..83 FT /note="Beta/gamma crystallin 'Greek key' 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028" FT DOMAIN 88..128 FT /note="Beta/gamma crystallin 'Greek key' 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028" FT DOMAIN 129..171 FT /note="Beta/gamma crystallin 'Greek key' 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028" FT REGION 84..87 FT /note="Connecting peptide" FT MOD_RES 23 FT /note="S-methylcysteine" FT /evidence="ECO:0000269|PubMed:12876325" FT VARIANT 5 FT /note="T -> P (in CTRCT2; reduces protein-protein FT interactions in vivo; dbSNP:rs104893618)" FT /evidence="ECO:0000269|PubMed:10521291, FT ECO:0000269|PubMed:12601044, ECO:0000269|PubMed:33243271" FT /id="VAR_021142" FT VARIANT 6 FT /note="F -> L (in dbSNP:rs2242072)" FT /id="VAR_038432" FT VARIANT 48 FT /note="R -> H (in dbSNP:rs61751949)" FT /evidence="ECO:0000269|PubMed:12011157, FT ECO:0000269|PubMed:21423869, ECO:0000269|PubMed:29386872" FT /id="VAR_021143" FT VARIANT 78 FT /note="S -> F (in CTRCT2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29914532" FT /id="VAR_084798" FT VARIANT 129 FT /note="G -> C (in CTRCT2; dbSNP:rs137853924)" FT /evidence="ECO:0000269|PubMed:22052681" FT /id="VAR_067212" FT VARIANT 144..174 FT /note="Missing (in CTRCT2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29386872" FT /id="VAR_084799" FT VARIANT 168 FT /note="R -> W (in CTRCT2; uncertain significance; FT dbSNP:rs28931604)" FT /evidence="ECO:0000269|PubMed:12011157, FT ECO:0000269|PubMed:18587492" FT /id="VAR_021144" FT STRAND 4..9 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 10..12 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 13..21 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 27..29 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 34..38 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 40..48 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 49..51 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 52..58 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 60..65 FT /evidence="ECO:0007829|PDB:2NBR" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 78..82 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 89..95 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 96..98 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 99..105 FT /evidence="ECO:0007829|PDB:2NBR" FT HELIX 112..115 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 122..129 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 137..139 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 140..146 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 148..151 FT /evidence="ECO:0007829|PDB:2NBR" FT TURN 154..158 FT /evidence="ECO:0007829|PDB:2NBR" FT STRAND 165..169 FT /evidence="ECO:0007829|PDB:2NBR" SQ SEQUENCE 174 AA; 20879 MW; B01DC167171A7668 CRC64; MGKITFYEDR AFQGRSYETT TDCPNLQPYF SRCNSIRVES GCWMLYERPN YQGQQYLLRR GEYPDYQQWM GLSDSIRSCC LIPQTVSHRL RLYEREDHKG LMMELSEDCP SIQDRFHLSE IRSLHVLEGC WVLYELPNYR GRQYLLRPQE YRRCQDWGAM DAKAGSLRRV VDLY //