CRBA1_HUMAN
ID CRBA1_HUMAN Reviewed; 215 AA.
AC P05813; Q13633; Q14CM9;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 4.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Beta-crystallin A3;
DE Contains:
DE RecName: Full=Beta-crystallin A3, isoform A1, Delta4 form;
DE Contains:
DE RecName: Full=Beta-crystallin A3, isoform A1, Delta7 form;
DE Contains:
DE RecName: Full=Beta-crystallin A3, isoform A1, Delta8 form;
GN Name=CRYBA1; Synonyms=CRYB1;
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=3745196; DOI=10.1016/s0021-9258(18)67257-6;
RA Hogg D., Tsui L.-C., Gorin M., Breitman M.L.;
RT "Characterization of the human beta-crystallin gene Hu beta A3/A1 reveals
RT ancestral relationships among the beta gamma-crystallin superfamily.";
RL J. Biol. Chem. 261:12420-12427(1986).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 44-215, PROTEIN SEQUENCE OF 23-30 AND
RP 197-211, ACETYLATION AT MET-1, CLEAVAGE OF INITIATOR METHIONINE (ISOFORM
RP A1), ACETYLATION AT ALA-2 (ISOFORM A1), AND MASS 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 [4]
RP PROTEOLYTIC PROCESSING OF N-TERMINUS, ACETYLATION AT MET-1, CLEAVAGE OF
RP INITIATOR METHIONINE (ISOFORM A1), ACETYLATION AT ALA-2 (ISOFORM A1),
RP METHYLATION AT CYS-82; CYS-117 AND CYS-185, GLUTATHIONYLATION AT CYS-82 AND
RP CYS-117, AND MASS SPECTROMETRY.
RX PubMed=15576560; DOI=10.1110/ps.04738505;
RA Lapko V.N., Cerny R.L., Smith D.L., Smith J.B.;
RT "Modifications of human betaA1/betaA3-crystallins include S-methylation,
RT glutathiolation, and truncation.";
RL Protein Sci. 14:45-54(2005).
RN [5]
RP INVOLVEMENT IN CTRCT10.
RX PubMed=9788845;
RA Kannabiran C., Rogan P.K., Olmos L., Basti S., Rao G.N., Kaiser-Kupfer M.,
RA Hejtmancik J.F.;
RT "Autosomal dominant zonular cataract with sutural opacities is associated
RT with a splice mutation in the betaA3/A1-crystallin gene.";
RL Mol. Vis. 4:21-21(1998).
RN [6]
RP INVOLVEMENT IN CTRCT10.
RX PubMed=15016766; DOI=10.1093/hmg/ddh110;
RA Reddy M.A., Bateman O.A., Chakarova C., Ferris J., Berry V., Lomas E.,
RA Sarra R., Smith M.A., Moore A.T., Bhattacharya S.S., Slingsby C.;
RT "Characterization of the G91del CRYBA1/3-crystallin protein: a cause of
RT human inherited cataract.";
RL Hum. Mol. Genet. 13:945-953(2004).
RN [7]
RP VARIANT CTRCT10 GLY-91 DEL.
RX PubMed=21866213;
RA Sun W., Xiao X., Li S., Guo X., Zhang Q.;
RT "Mutation analysis of 12 genes in Chinese families with congenital
RT cataracts.";
RL Mol. Vis. 17:2197-2206(2011).
RN [8]
RP VARIANT CTRCT10 GLY-91 DEL.
RX PubMed=31523120;
RA Zhuang J., Cao Z., Zhu Y., Liu L., Tong Y., Chen X., Wang Y., Lu C., Ma X.,
RA Yang J.;
RT "Mutation screening of crystallin genes in Chinese families with congenital
RT cataracts.";
RL Mol. Vis. 25:427-437(2019).
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 P05813; Q03989: ARID5A; NbExp=3; IntAct=EBI-7043337, EBI-948603;
CC P05813; Q9H503-2: BANF2; NbExp=3; IntAct=EBI-7043337, EBI-11977289;
CC P05813; Q96J87-2: CELF6; NbExp=3; IntAct=EBI-7043337, EBI-12832044;
CC P05813; Q8TCT0: CERK; NbExp=3; IntAct=EBI-7043337, EBI-10274247;
CC P05813; Q9Y6H1: CHCHD2; NbExp=3; IntAct=EBI-7043337, EBI-2321769;
CC P05813; P02511: CRYAB; NbExp=2; IntAct=EBI-7043337, EBI-739060;
CC P05813; P53674: CRYBB1; NbExp=9; IntAct=EBI-7043337, EBI-7519424;
CC P05813; P43320: CRYBB2; NbExp=3; IntAct=EBI-7043337, EBI-974082;
CC P05813; P26998: CRYBB3; NbExp=6; IntAct=EBI-7043337, EBI-1965681;
CC P05813; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7043337, EBI-3867333;
CC P05813; O75593: FOXH1; NbExp=3; IntAct=EBI-7043337, EBI-1759806;
CC P05813; P31273: HOXC8; NbExp=3; IntAct=EBI-7043337, EBI-1752118;
CC P05813; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-7043337, EBI-1052037;
CC P05813; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-7043337, EBI-11953846;
CC P05813; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-7043337, EBI-10241252;
CC P05813; Q14847-2: LASP1; NbExp=3; IntAct=EBI-7043337, EBI-9088686;
CC P05813; Q86UR1-2: NOXA1; NbExp=3; IntAct=EBI-7043337, EBI-12025760;
CC P05813; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-7043337, EBI-742388;
CC P05813; O75360: PROP1; NbExp=3; IntAct=EBI-7043337, EBI-9027467;
CC P05813; Q93062: RBPMS; NbExp=3; IntAct=EBI-7043337, EBI-740322;
CC P05813; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-7043337, EBI-372094;
CC P05813; Q08AM6: VAC14; NbExp=3; IntAct=EBI-7043337, EBI-2107455;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=A3;
CC IsoId=P05813-1; Sequence=Displayed;
CC Name=A1;
CC IsoId=P05813-2; Sequence=VSP_018710;
CC -!- DOMAIN: Has a two-domain beta-structure, folded into four very similar
CC Greek key motifs.
CC -!- PTM: Specific cleavages in the N-terminal arm occur during lens
CC maturation and give rise to several truncated forms. Cleavages do not
CC seem to have adverse effects on solubility.
CC {ECO:0000269|PubMed:15576560}.
CC -!- PTM: S-methylation and glutathionylation occur in normal young lenses
CC and do not seem to be detrimental. {ECO:0000269|PubMed:15576560}.
CC -!- MASS SPECTROMETRY: [Beta-crystallin A3]: Mass=25192; Mass_error=3;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:8999933};
CC -!- MASS SPECTROMETRY: [Beta-crystallin A3]: Mass=25192;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:15576560};
CC -!- MASS SPECTROMETRY: [Beta-crystallin A3, isoform A1, Delta4 form]:
CC Mass=22646; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15576560};
CC -!- MASS SPECTROMETRY: [Beta-crystallin A3, isoform A1, Delta7 form]:
CC Mass=22351; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15576560};
CC -!- MASS SPECTROMETRY: [Beta-crystallin A3, isoform A1, Delta8 form]:
CC Mass=22294; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15576560};
CC -!- DISEASE: Cataract 10, multiple types (CTRCT10) [MIM:600881]: 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. CTRCT10 includes congenital zonular with sutural
CC opacities, among others. This is a form of zonular cataract with an
CC erect Y-shaped anterior and an inverted Y-shaped posterior sutural
CC opacities. Zonular or lamellar cataracts are opacities, broad or
CC narrow, usually consisting of powdery white dots affecting only certain
CC layers or zones between the cortex and nucleus of an otherwise clear
CC 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:15016766, ECO:0000269|PubMed:21866213,
CC ECO:0000269|PubMed:31523120, ECO:0000269|PubMed:9788845}. 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 -!- WEB RESOURCE: Name=Eye disease Crystallin, beta-A1 (CRYBA1);
CC Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/CRYBA1";
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DR EMBL; M14306; AAA52107.1; -; Genomic_DNA.
DR EMBL; M14301; AAA52107.1; JOINED; Genomic_DNA.
DR EMBL; M14302; AAA52107.1; JOINED; Genomic_DNA.
DR EMBL; M14303; AAA52107.1; JOINED; Genomic_DNA.
DR EMBL; M14304; AAA52107.1; JOINED; Genomic_DNA.
DR EMBL; M14305; AAA52107.1; JOINED; Genomic_DNA.
DR EMBL; BC069537; AAH69537.1; -; mRNA.
DR EMBL; BC113693; AAI13694.1; -; mRNA.
DR EMBL; U59058; AAC50971.1; -; mRNA.
DR CCDS; CCDS11249.1; -. [P05813-1]
DR PIR; A25202; CYHUB3.
DR RefSeq; NP_005199.2; NM_005208.4. [P05813-1]
DR AlphaFoldDB; P05813; -.
DR SMR; P05813; -.
DR BioGRID; 107801; 41.
DR IntAct; P05813; 22.
DR MINT; P05813; -.
DR STRING; 9606.ENSP00000225387; -.
DR iPTMnet; P05813; -.
DR PhosphoSitePlus; P05813; -.
DR BioMuta; CRYBA1; -.
DR DMDM; 2506317; -.
DR EPD; P05813; -.
DR MassIVE; P05813; -.
DR PaxDb; P05813; -.
DR PeptideAtlas; P05813; -.
DR PRIDE; P05813; -.
DR ProteomicsDB; 51859; -. [P05813-1]
DR ProteomicsDB; 51860; -. [P05813-2]
DR Antibodypedia; 26701; 183 antibodies from 25 providers.
DR DNASU; 1411; -.
DR Ensembl; ENST00000225387.8; ENSP00000225387.3; ENSG00000108255.8. [P05813-1]
DR GeneID; 1411; -.
DR KEGG; hsa:1411; -.
DR MANE-Select; ENST00000225387.8; ENSP00000225387.3; NM_005208.5; NP_005199.2.
DR UCSC; uc002hdw.4; human. [P05813-1]
DR CTD; 1411; -.
DR DisGeNET; 1411; -.
DR GeneCards; CRYBA1; -.
DR HGNC; HGNC:2394; CRYBA1.
DR HPA; ENSG00000108255; Tissue enriched (brain).
DR MalaCards; CRYBA1; -.
DR MIM; 123610; gene.
DR MIM; 600881; phenotype.
DR neXtProt; NX_P05813; -.
DR OpenTargets; ENSG00000108255; -.
DR Orphanet; 441452; Early-onset lamellar cataract.
DR Orphanet; 98991; Early-onset nuclear cataract.
DR Orphanet; 98993; Early-onset posterior polar cataract.
DR Orphanet; 98985; Early-onset sutural cataract.
DR PharmGKB; PA26908; -.
DR VEuPathDB; HostDB:ENSG00000108255; -.
DR eggNOG; ENOG502QSM0; Eukaryota.
DR GeneTree; ENSGT00940000159685; -.
DR HOGENOM; CLU_081883_0_0_1; -.
DR InParanoid; P05813; -.
DR OMA; IGRQWEM; -.
DR OrthoDB; 1142622at2759; -.
DR PhylomeDB; P05813; -.
DR TreeFam; TF331401; -.
DR PathwayCommons; P05813; -.
DR SignaLink; P05813; -.
DR BioGRID-ORCS; 1411; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; CRYBA1; human.
DR GeneWiki; Crystallin,_beta_A1; -.
DR GenomeRNAi; 1411; -.
DR Pharos; P05813; Tbio.
DR PRO; PR:P05813; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P05813; protein.
DR Bgee; ENSG00000108255; Expressed in lens of camera-type eye and 101 other tissues.
DR ExpressionAtlas; P05813; baseline and differential.
DR Genevisible; P05813; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS: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:0001818; P:negative regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR GO; GO:2000210; P:positive regulation of anoikis; IEA:Ensembl.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IBA:GO_Central.
DR InterPro; IPR001064; Beta/gamma_crystallin.
DR InterPro; IPR011024; G_crystallin-like.
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 Acetylation; Alternative initiation; Cataract; Direct protein sequencing;
KW Disease variant; Eye lens protein; Glutathionylation; Methylation;
KW Oxidation; Reference proteome; Repeat.
FT CHAIN 1..215
FT /note="Beta-crystallin A3"
FT /id="PRO_0000006331"
FT CHAIN 23..215
FT /note="Beta-crystallin A3, isoform A1, Delta4 form"
FT /id="PRO_0000226692"
FT CHAIN 26..215
FT /note="Beta-crystallin A3, isoform A1, Delta7 form"
FT /id="PRO_0000226693"
FT CHAIN 27..215
FT /note="Beta-crystallin A3, isoform A1, Delta8 form"
FT /id="PRO_0000226694"
FT DOMAIN 31..70
FT /note="Beta/gamma crystallin 'Greek key' 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 71..117
FT /note="Beta/gamma crystallin 'Greek key' 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 124..165
FT /note="Beta/gamma crystallin 'Greek key' 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT DOMAIN 166..214
FT /note="Beta/gamma crystallin 'Greek key' 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00028"
FT REGION 1..30
FT /note="N-terminal arm"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..123
FT /note="Connecting peptide"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:15576560,
FT ECO:0000269|PubMed:8999933"
FT MOD_RES 82
FT /note="S-glutathionyl cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:15576560"
FT MOD_RES 82
FT /note="S-methylcysteine; alternate"
FT /evidence="ECO:0000269|PubMed:15576560"
FT MOD_RES 117
FT /note="S-glutathionyl cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:15576560"
FT MOD_RES 117
FT /note="S-methylcysteine; alternate"
FT /evidence="ECO:0000269|PubMed:15576560"
FT MOD_RES 185
FT /note="S-methylcysteine"
FT /evidence="ECO:0000269|PubMed:15576560"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform A1)"
FT /evidence="ECO:0000305"
FT /id="VSP_018710"
FT VARIANT 91
FT /note="Missing (in CTRCT10)"
FT /evidence="ECO:0000269|PubMed:21866213,
FT ECO:0000269|PubMed:31523120"
FT /id="VAR_084782"
FT CONFLICT 107
FT /note="I -> M (in Ref. 1; AAA52107)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="I -> F (in Ref. 1; AAA52107)"
FT /evidence="ECO:0000305"
FT CONFLICT 172..174
FT /note="QYP -> HYL (in Ref. 1; AAA52107)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="E -> K (in Ref. 1; AAA52107)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="G -> E (in Ref. 1; AAA52107)"
FT /evidence="ECO:0000305"
FT INIT_MET P05813-2:1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15576560,
FT ECO:0000269|PubMed:8999933"
FT MOD_RES P05813-2:2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:15576560,
FT ECO:0000269|PubMed:8999933"
SQ SEQUENCE 215 AA; 25150 MW; C544564835688A19 CRC64;
METQAEQQEL ETLPTTKMAQ TNPTPGSLGP WKITIYDQEN FQGKRMEFTS SCPNVSERSF
DNVRSLKVES GAWIGYEHTS FCGQQFILER GEYPRWDAWS GSNAYHIERL MSFRPICSAN
HKESKMTIFE KENFIGRQWE ISDDYPSLQA MGWFNNEVGS MKIQSGAWVC YQYPGYRGYQ
YILECDHHGG DYKHWREWGS HAQTSQIQSI RRIQQ
