CRBA4_HUMAN
ID CRBA4_HUMAN Reviewed; 196 AA.
AC P53673; Q4VB22; Q6ICE4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Beta-crystallin A4;
DE AltName: Full=Beta-A4 crystallin;
GN Name=CRYBA4;
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 [MRNA], PROTEIN SEQUENCE OF 14-25; 159-174 AND 178-192,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, AND MASS
RP SPECTROMETRY.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-194.
RX PubMed=7504514; DOI=10.1002/gcc.2870080208;
RA Bijlsma E.K., Delattre O., Juyn J.A., Melot T., Westerveld A.,
RA Dumanski J.P., Thomas G., Hulsebos T.J.M.;
RT "Regional fine mapping of the beta crystallin genes on chromosome 22
RT excludes these genes as physically linked markers for neurofibromatosis
RT type 2.";
RL Genes Chromosomes Cancer 8:112-118(1993).
RN [6]
RP INVOLVEMENT IN CTRCT23, AND VARIANTS CTRCT23 PRO-69 AND SER-94.
RX PubMed=16960806; DOI=10.1086/507712;
RA Billingsley G., Santhiya S.T., Paterson A.D., Ogata K., Wodak S.,
RA Hosseini S.M., Manisastry S.M., Vijayalakshmi P., Gopinath P.M., Graw J.,
RA Heon E.;
RT "CRYBA4, a novel human cataract gene, is also involved in microphthalmia.";
RL Am. J. Hum. Genet. 79:702-709(2006).
RN [7]
RP INVOLVEMENT IN CTRCT23, AND VARIANT CTRCT23 TRP-64.
RX PubMed=20577656;
RA Zhou G., Zhou N., Hu S., Zhao L., Zhang C., Qi Y.;
RT "A missense mutation in CRYBA4 associated with congenital cataract and
RT microcornea.";
RL Mol. Vis. 16:1019-1024(2010).
CC -!- FUNCTION: Crystallins are the dominant structural components of the
CC vertebrate eye lens.
CC -!- SUBUNIT: Homo/heterodimer, or complexes of higher-order. The structure
CC of beta-crystallin oligomers seems to be stabilized through
CC interactions between the N-terminal arms (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P53673; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-7519711, EBI-946029;
CC P53673; Q8N5R6: CCDC33; NbExp=3; IntAct=EBI-7519711, EBI-740841;
CC P53673; Q8TAP6: CEP76; NbExp=9; IntAct=EBI-7519711, EBI-742887;
CC P53673; P53673: CRYBA4; NbExp=6; IntAct=EBI-7519711, EBI-7519711;
CC P53673; P53674: CRYBB1; NbExp=3; IntAct=EBI-7519711, EBI-7519424;
CC P53673; Q12805: EFEMP1; NbExp=3; IntAct=EBI-7519711, EBI-536772;
CC P53673; Q5TD97: FHL5; NbExp=3; IntAct=EBI-7519711, EBI-750641;
CC P53673; P08151: GLI1; NbExp=3; IntAct=EBI-7519711, EBI-308084;
CC P53673; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-7519711, EBI-747204;
CC P53673; A9UHW6-2: MIF4GD; NbExp=3; IntAct=EBI-7519711, EBI-9118295;
CC P53673; O75558: STX11; NbExp=3; IntAct=EBI-7519711, EBI-714135;
CC P53673; Q15654: TRIP6; NbExp=3; IntAct=EBI-7519711, EBI-742327;
CC -!- DOMAIN: Has a two-domain beta-structure, folded into four very similar
CC Greek key motifs.
CC -!- MASS SPECTROMETRY: Mass=22285; Mass_error=3; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8999933};
CC -!- DISEASE: Cataract 23, multiple types (CTRCT23) [MIM:610425]: 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. In general, the more posteriorly located and
CC dense an opacity, the greater the impact on visual function. CTRCT23 is
CC a zonular cataract. Zonular or lamellar cataracts are opacities, broad
CC or narrow, usually consisting of powdery white dots affecting only
CC certain layers or zones between the cortex and nucleus of an otherwise
CC clear lens. The opacity may be so dense as to render the entire central
CC region of the lens completely opaque, or so translucent that vision is
CC hardly if at all impeded. Zonular cataracts generally do not involve
CC the embryonic nucleus, though sometimes they involve the fetal nucleus.
CC Usually sharply separated from a clear cortex outside them, they may
CC have projections from their outer edges known as riders or spokes.
CC {ECO:0000269|PubMed:16960806, ECO:0000269|PubMed:20577656}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the beta/gamma-crystallin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAG30310.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U59057; AAC50970.1; -; mRNA.
DR EMBL; CR456424; CAG30310.1; ALT_INIT; mRNA.
DR EMBL; Z95115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069404; AAH69404.1; -; mRNA.
DR EMBL; BC096171; AAH96171.1; -; mRNA.
DR EMBL; BC096172; AAH96172.1; -; mRNA.
DR EMBL; BC096173; AAH96173.1; -; mRNA.
DR EMBL; BC096174; AAH96174.1; -; mRNA.
DR EMBL; S67583; AAD13994.1; -; Genomic_DNA.
DR CCDS; CCDS13841.1; -.
DR PIR; I54083; I54083.
DR RefSeq; NP_001877.1; NM_001886.2.
DR RefSeq; XP_016884087.1; XM_017028598.1.
DR PDB; 3LWK; X-ray; 1.70 A; A=8-196.
DR PDBsum; 3LWK; -.
DR AlphaFoldDB; P53673; -.
DR SMR; P53673; -.
DR BioGRID; 107803; 38.
DR IntAct; P53673; 26.
DR MINT; P53673; -.
DR STRING; 9606.ENSP00000346805; -.
DR iPTMnet; P53673; -.
DR PhosphoSitePlus; P53673; -.
DR BioMuta; CRYBA4; -.
DR DMDM; 2506318; -.
DR MassIVE; P53673; -.
DR PaxDb; P53673; -.
DR PeptideAtlas; P53673; -.
DR PRIDE; P53673; -.
DR ProteomicsDB; 56606; -.
DR Antibodypedia; 24295; 141 antibodies from 22 providers.
DR DNASU; 1413; -.
DR Ensembl; ENST00000354760.4; ENSP00000346805.3; ENSG00000196431.4.
DR GeneID; 1413; -.
DR KEGG; hsa:1413; -.
DR MANE-Select; ENST00000354760.4; ENSP00000346805.3; NM_001886.3; NP_001877.1.
DR UCSC; uc003acz.4; human.
DR CTD; 1413; -.
DR DisGeNET; 1413; -.
DR GeneCards; CRYBA4; -.
DR HGNC; HGNC:2396; CRYBA4.
DR HPA; ENSG00000196431; Tissue enhanced (epididymis, testis).
DR MalaCards; CRYBA4; -.
DR MIM; 123631; gene.
DR MIM; 610425; phenotype.
DR neXtProt; NX_P53673; -.
DR OpenTargets; ENSG00000196431; -.
DR Orphanet; 1377; Cataract-microcornea syndrome.
DR Orphanet; 441452; Early-onset lamellar cataract.
DR PharmGKB; PA26910; -.
DR VEuPathDB; HostDB:ENSG00000196431; -.
DR eggNOG; ENOG502QTF8; Eukaryota.
DR GeneTree; ENSGT00940000160372; -.
DR HOGENOM; CLU_081883_0_0_1; -.
DR InParanoid; P53673; -.
DR OMA; GEYPSWE; -.
DR OrthoDB; 1142622at2759; -.
DR PhylomeDB; P53673; -.
DR TreeFam; TF331401; -.
DR PathwayCommons; P53673; -.
DR SignaLink; P53673; -.
DR BioGRID-ORCS; 1413; 10 hits in 1070 CRISPR screens.
DR ChiTaRS; CRYBA4; human.
DR EvolutionaryTrace; P53673; -.
DR GeneWiki; CRYBA4; -.
DR GenomeRNAi; 1413; -.
DR Pharos; P53673; Tbio.
DR PRO; PR:P53673; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P53673; protein.
DR Bgee; ENSG00000196431; Expressed in granulocyte and 57 other tissues.
DR ExpressionAtlas; P53673; baseline and differential.
DR Genevisible; P53673; HS.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005212; F:structural constituent of eye lens; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IMP:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR001064; Beta/gamma_crystallin.
DR InterPro; IPR033342; CRYBA4.
DR InterPro; IPR011024; G_crystallin-like.
DR PANTHER; PTHR11818:SF19; PTHR11818:SF19; 1.
DR Pfam; PF00030; Crystall; 2.
DR PRINTS; PR01367; BGCRYSTALLIN.
DR SMART; SM00247; XTALbg; 2.
DR SUPFAM; SSF49695; SSF49695; 1.
DR PROSITE; PS50915; CRYSTALLIN_BETA_GAMMA; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cataract; Direct protein sequencing;
KW Disease variant; Eye lens protein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8999933"
FT CHAIN 2..196
FT /note="Beta-crystallin A4"
FT /id="PRO_0000057545"
FT DOMAIN 12..51
FT /note="Beta/gamma crystallin 'Greek key' 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 52..98
FT /note="Beta/gamma crystallin 'Greek key' 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 105..146
FT /note="Beta/gamma crystallin 'Greek key' 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 147..195
FT /note="Beta/gamma crystallin 'Greek key' 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT REGION 2..11
FT /note="N-terminal arm"
FT REGION 99..104
FT /note="Connecting peptide"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|PubMed:8999933"
FT VARIANT 36
FT /note="V -> M (in dbSNP:rs35520672)"
FT /id="VAR_033824"
FT VARIANT 64
FT /note="G -> W (in CTRCT23; dbSNP:rs1114167427)"
FT /evidence="ECO:0000269|PubMed:20577656"
FT /id="VAR_078868"
FT VARIANT 69
FT /note="L -> P (in CTRCT23; the patient has cataract and
FT bilateral microphthalmia; the mutation is predicted to
FT disrupt the beta-sheet structure of the protein;
FT dbSNP:rs74315487)"
FT /evidence="ECO:0000269|PubMed:16960806"
FT /id="VAR_029528"
FT VARIANT 84
FT /note="T -> M (in dbSNP:rs4277)"
FT /id="VAR_014903"
FT VARIANT 94
FT /note="F -> S (in CTRCT23; modeling suggests that this
FT substitution would significantly reduce the intrinsic
FT stability of the crystalline monomer; dbSNP:rs74315486)"
FT /evidence="ECO:0000269|PubMed:16960806"
FT /id="VAR_029529"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 20..22
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 141..154
FT /evidence="ECO:0007829|PDB:3LWK"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 158..165
FT /evidence="ECO:0007829|PDB:3LWK"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:3LWK"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:3LWK"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:3LWK"
SQ SEQUENCE 196 AA; 22374 MW; 104EC68E3CDE5740 CRC64;
MTLQCTKSAG PWKMVVWDED GFQGRRHEFT AECPSVLELG FETVRSLKVL SGAWVGFEHA
GFQGQQYILE RGEYPSWDAW GGNTAYPAER LTSFRPAACA NHRDSRLTIF EQENFLGKKG
ELSDDYPSLQ AMGWEGNEVG SFHVHSGAWV CSQFPGYRGF QYVLECDHHS GDYKHFREWG
SHAPTFQVQS IRRIQQ
