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   24-JAN-2024, entry version 209.
DE   RecName: Full=Beta-crystallin A3 {ECO:0000305};
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 {ECO:0000312|HGNC:HGNC:2394}; 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   INTERACTION WITH SLC36A4.
RX   PubMed=28083894; DOI=10.1111/acel.12561;
RA   Shang P., Valapala M., Grebe R., Hose S., Ghosh S., Bhutto I.A.,
RA   Handa J.T., Lutty G.A., Lu L., Wan J., Qian J., Sergeev Y., Puertollano R.,
RA   Zigler J.S. Jr., Xu G.T., Sinha D.;
RT   "The amino acid transporter SLC36A4 regulates the amino acid pool in
RT   retinal pigmented epithelial cells and mediates the mechanistic target of
RT   rapamycin, complex 1 signaling.";
RL   Aging Cell 16:349-359(2017).
RN   [6]
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   [7]
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   [8]
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   [9]
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). Interacts
CC       with CRYBA1 (PubMed:28083894). {ECO:0000250,
CC       ECO:0000269|PubMed:28083894}.
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; 9606-ENSP00000225387; -.
DR   PeptideAtlas; P05813; -.
DR   ProteomicsDB; 51859; -. [P05813-1]
DR   ProteomicsDB; 51860; -. [P05813-2]
DR   Antibodypedia; 26701; 189 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   AGR; HGNC:2394; -.
DR   CTD; 1411; -.
DR   DisGeNET; 1411; -.
DR   GeneCards; CRYBA1; -.
DR   HGNC; HGNC:2394; CRYBA1.
DR   HPA; ENSG00000108255; Not detected.
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; 3998747at2759; -.
DR   PhylomeDB; P05813; -.
DR   TreeFam; TF331401; -.
DR   PathwayCommons; P05813; -.
DR   SignaLink; P05813; -.
DR   BioGRID-ORCS; 1411; 12 hits in 1149 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 102 other cell types or tissues.
DR   ExpressionAtlas; P05813; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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   Gene3D; 2.60.20.10; Crystallins; 2.
DR   InterPro; IPR001064; Beta/gamma_crystallin.
DR   InterPro; IPR011024; G_crystallin-like.
DR   PANTHER; PTHR11818:SF8; BETA-CRYSTALLIN A3; 1.
DR   PANTHER; PTHR11818; BETA/GAMMA CRYSTALLIN; 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; P05813; HS.
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
//