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Protein

Alpha-crystallin A chain

Gene

CRYAA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Contributes to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1Susceptible to oxidation1
Sitei18Susceptible to oxidation1
Sitei34Susceptible to oxidation1
Metal bindingi79Zinc 1Curated1
Metal bindingi100Zinc 2By similarity1
Metal bindingi102Zinc 2By similarity1
Metal bindingi107Zinc 1Curated1
Metal bindingi115Zinc 1Curated1
Sitei138Susceptible to oxidation1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • structural constituent of eye lens Source: UniProtKB-KW
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of intracellular transport Source: HGNC
  • protein homooligomerization Source: UniProtKB
  • response to stimulus Source: UniProtKB-KW
  • visual perception Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Eye lens protein

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160202-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-crystallin A chain
Alternative name(s):
Heat shock protein beta-4
Short name:
HspB4
Cleaved into the following 3 chains:
Gene namesi
Name:CRYAA
Synonyms:CRYA1, HSPB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:2388. CRYAA.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Alpha-crystallin A 1-172 is found at nearly twofold higher levels in diabetic lenses than in age-matched control lenses.

Cataract 9, multiple types (CTRCT9)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT9 includes nuclear, zonular central nuclear, anterior polar, cortical, embryonal, anterior subcapsular, fan-shaped, and total cataracts, among others. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
See also OMIM:604219
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07003212R → C in CTRCT9. 1 PublicationCorresponds to variant rs397515624dbSNPEnsembl.1
Natural variantiVAR_04689221R → L in CTRCT9; associated with macular hypoplasia and a generally hypopigmented fundus. 1 Publication1
Natural variantiVAR_03837549R → C in CTRCT9; nuclear cataract. 1 PublicationCorresponds to variant rs74315441dbSNPEnsembl.1
Natural variantiVAR_003819116R → C in CTRCT9; zonular central nuclear cataract; reduced chaperone-like activity and increased membrane-binding capacity. 2 PublicationsCorresponds to variant rs74315439dbSNPEnsembl.1
Natural variantiVAR_046893116R → H in CTRCT9; reverse phase-high-performance liquid chromatography suggests an increase hydrophobicity of the mutant protein; loss of chaperone activity of the mutant is seen in DL-dithiothreitol-induced insulin aggregation assay; fast protein liquid chromatography purification shows that the mutant protein has increased binding affinity to lysozyme. 2 PublicationsCorresponds to variant rs121912973dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi123N → D: Impairs chaperone activity. 1 Publication1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi102724652.
1409.
MalaCardsiCRYAA.
MIMi604219. phenotype.
OpenTargetsiENSG00000160202.
ENSG00000276076.
Orphaneti1377. Cataract-microcornea syndrome.
98991. Nuclear cataract.
98995. Zonular cataract.
PharmGKBiPA26906.

Polymorphism and mutation databases

BioMutaiCRYAA.
DMDMi1706112.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001258651 – 173Alpha-crystallin A chainAdd BLAST173
ChainiPRO_00002266391 – 172Alpha-crystallin A(1-172)Add BLAST172
ChainiPRO_00004235031 – 168Alpha-crystallin A(1-168)Add BLAST168
ChainiPRO_00004235041 – 162Alpha-crystallin A(1-162)Add BLAST162

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1
Modified residuei6Deamidated glutamine; partial1 Publication1
Modified residuei45Phosphoserine1 Publication1
Modified residuei50Deamidated glutamine; partial1 Publication1
Modified residuei70N6-acetyllysine2 Publications1
Modified residuei90Deamidated glutamine; partial1 Publication1
Modified residuei99N6-acetyllysine1 Publication1
Modified residuei101Deamidated asparagine; partial4 Publications1
Modified residuei122Phosphoserine3 Publications1
Modified residuei123Deamidated asparagine; partial1 Publication1
Disulfide bondi131 ↔ 1422 Publications
Modified residuei147Deamidated glutamine; partial1 Publication1
Glycosylationi162O-linked (GlcNAc)By similarity1

Post-translational modificationi

O-glycosylated; contains N-acetylglucosamine side chains.
Deamidation of Asn-101 in lens occurs mostly during the first 30 years of age, followed by a small additional amount of deamidation (approximately 5%) during the next approximately 38 years, resulting in a maximum of approximately 50% deamidation during the lifetime of the individual.5 Publications
Phosphorylation on Ser-122 seems to be developmentally regulated. Absent in the first months of life, it appears during the first 12 years of human lifetime. The relative amount of phosphorylated form versus unphosphorylated form does not change over the lifetime of the individual.5 Publications
Acetylation at Lys-70 seems to increase chaperone activity.3 Publications
Undergoes age-dependent proteolytical cleavage at the C-terminus. Alpha-crystallin A(1-172) is the most predominant form produced most rapidly during the first 12 years of age and after this age is present in approximatley 50% of the lens molecules.5 Publications

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Oxidation, Phosphoprotein

Proteomic databases

EPDiP02489.
PaxDbiP02489.
PeptideAtlasiP02489.
PRIDEiP02489.

2D gel databases

SWISS-2DPAGEP02489.

PTM databases

iPTMnetiP02489.
PhosphoSitePlusiP02489.
UniCarbKBiP02489.

Expressioni

Tissue specificityi

Expressed in eye lens.1 Publication

Gene expression databases

BgeeiENSG00000160202.
CleanExiHS_CRYAA.
ExpressionAtlasiP02489. baseline and differential.
GenevisibleiP02489. HS.

Organism-specific databases

HPAiCAB034116.

Interactioni

Subunit structurei

Heteropolymer composed of three CRYAA and one CRYAB subunits. Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens. Can also form homodimers and higher homooligomers. Age-dependent C-terminal truncation affects oligomerization.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-6875961,EBI-6875961
CRYABP0251111EBI-6875961,EBI-739060
CRYGCP073153EBI-6875961,EBI-6875941
GORASP2Q9H8Y86EBI-6875961,EBI-739467
HEL-S-101V9HW273EBI-6875961,EBI-10178933
HSPB6O145584EBI-6875961,EBI-739095
SDCBPO005605EBI-6875961,EBI-727004
SPG21Q9NZD85EBI-6875961,EBI-742688
WDYHV1Q96HA85EBI-6875961,EBI-741158

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107799. 16 interactors.
DIPiDIP-41265N.
IntActiP02489. 10 interactors.
MINTiMINT-220977.
STRINGi9606.ENSP00000291554.

Structurei

3D structure databases

DisProtiDP00444.
ProteinModelPortaliP02489.
SMRiP02489.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the small heat shock protein (HSP20) family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3591. Eukaryota.
ENOG410YERS. LUCA.
GeneTreeiENSGT00760000119238.
HOGENOMiHOG000233954.
HOVERGENiHBG054766.
InParanoidiP02489.
KOiK09541.
OMAiGPKVQSG.
OrthoDBiEOG091G0USC.
PhylomeDBiP02489.
TreeFamiTF105049.

Family and domain databases

Gene3Di2.60.40.790. 1 hit.
InterProiIPR002068. A-crystallin/Hsp20_dom.
IPR001436. Alpha-crystallin/HSP.
IPR012274. Alpha-crystallin_A.
IPR003090. Alpha-crystallin_N.
IPR031107. HSP20.
IPR008978. HSP20-like_chaperone.
[Graphical view]
PANTHERiPTHR11527. PTHR11527. 1 hit.
PTHR11527:SF36. PTHR11527:SF36. 1 hit.
PfamiPF00525. Crystallin. 1 hit.
PF00011. HSP20. 1 hit.
[Graphical view]
PIRSFiPIRSF036514. Sm_HSP_B1. 1 hit.
PRINTSiPR00299. ACRYSTALLIN.
SUPFAMiSSF49764. SSF49764. 1 hit.
PROSITEiPS01031. HSP20. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02489-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVTIQHPWF KRTLGPFYPS RLFDQFFGEG LFEYDLLPFL SSTISPYYRQ
60 70 80 90 100
SLFRTVLDSG ISEVRSDRDK FVIFLDVKHF SPEDLTVKVQ DDFVEIHGKH
110 120 130 140 150
NERQDDHGYI SREFHRRYRL PSNVDQSALS CSLSADGMLT FCGPKIQTGL
160 170
DATHAERAIP VSREEKPTSA PSS
Length:173
Mass (Da):19,909
Last modified:October 1, 1996 - v2
Checksum:i81804A8439837D50
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45S → T in AAA52105 (PubMed:3758227).Curated1
Sequence conflicti153 – 155THA → HT (PubMed:8587135).Curated3

Mass spectrometryi

Molecular mass is 19950 Da from positions 1 - 173. Determined by ESI. 1 Publication
Molecular mass is 19863 Da from positions 1 - 172. Determined by ESI. 1 Publication
Molecular mass is 20029 Da from positions 1 - 173. Determined by ESI. With 1 phosphate group.1 Publication
Molecular mass is 19951 Da from positions 1 - 173. Determined by ESI. 1 Publication
Molecular mass is 19864 Da from positions 1 - 172. Determined by ESI. 1 Publication
Molecular mass is 19947 Da from positions 1 - 173. Determined by ESI. 1 Publication
Molecular mass is 19851 Da from positions 1 - 172. Determined by ESI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07003212R → C in CTRCT9. 1 PublicationCorresponds to variant rs397515624dbSNPEnsembl.1
Natural variantiVAR_04689221R → L in CTRCT9; associated with macular hypoplasia and a generally hypopigmented fundus. 1 Publication1
Natural variantiVAR_03837549R → C in CTRCT9; nuclear cataract. 1 PublicationCorresponds to variant rs74315441dbSNPEnsembl.1
Natural variantiVAR_036564105D → H in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_003819116R → C in CTRCT9; zonular central nuclear cataract; reduced chaperone-like activity and increased membrane-binding capacity. 2 PublicationsCorresponds to variant rs74315439dbSNPEnsembl.1
Natural variantiVAR_046893116R → H in CTRCT9; reverse phase-high-performance liquid chromatography suggests an increase hydrophobicity of the mutant protein; loss of chaperone activity of the mutant is seen in DL-dithiothreitol-induced insulin aggregation assay; fast protein liquid chromatography purification shows that the mutant protein has increased binding affinity to lysozyme. 2 PublicationsCorresponds to variant rs121912973dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05569 mRNA. Translation: AAA97523.1.
U66584 mRNA. Translation: AAC50900.1.
X14789 mRNA. Translation: CAA32891.1.
CR407691 mRNA. Translation: CAG28619.1.
AP001631 Genomic DNA. No translation available.
AP001748 Genomic DNA. Translation: BAA95535.1.
CH471079 Genomic DNA. Translation: EAX09497.1.
CH471079 Genomic DNA. Translation: EAX09498.1.
BC069528 mRNA. Translation: AAH69528.1.
BC113598 mRNA. Translation: AAI13599.1.
M35628 Genomic DNA. Translation: AAA52106.1.
M35629 Genomic DNA. Translation: AAA52105.1.
CCDSiCCDS13695.1.
PIRiS03344. CYHUAA.
RefSeqiNP_000385.1. NM_000394.3.
NP_001300979.1. NM_001314050.2.
UniGeneiHs.184085.

Genome annotation databases

EnsembliENST00000291554; ENSP00000291554; ENSG00000160202.
GeneIDi102724652.
1409.
KEGGihsa:102724652.
hsa:1409.
UCSCiuc002zdd.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05569 mRNA. Translation: AAA97523.1.
U66584 mRNA. Translation: AAC50900.1.
X14789 mRNA. Translation: CAA32891.1.
CR407691 mRNA. Translation: CAG28619.1.
AP001631 Genomic DNA. No translation available.
AP001748 Genomic DNA. Translation: BAA95535.1.
CH471079 Genomic DNA. Translation: EAX09497.1.
CH471079 Genomic DNA. Translation: EAX09498.1.
BC069528 mRNA. Translation: AAH69528.1.
BC113598 mRNA. Translation: AAI13599.1.
M35628 Genomic DNA. Translation: AAA52106.1.
M35629 Genomic DNA. Translation: AAA52105.1.
CCDSiCCDS13695.1.
PIRiS03344. CYHUAA.
RefSeqiNP_000385.1. NM_000394.3.
NP_001300979.1. NM_001314050.2.
UniGeneiHs.184085.

3D structure databases

DisProtiDP00444.
ProteinModelPortaliP02489.
SMRiP02489.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107799. 16 interactors.
DIPiDIP-41265N.
IntActiP02489. 10 interactors.
MINTiMINT-220977.
STRINGi9606.ENSP00000291554.

PTM databases

iPTMnetiP02489.
PhosphoSitePlusiP02489.
UniCarbKBiP02489.

Polymorphism and mutation databases

BioMutaiCRYAA.
DMDMi1706112.

2D gel databases

SWISS-2DPAGEP02489.

Proteomic databases

EPDiP02489.
PaxDbiP02489.
PeptideAtlasiP02489.
PRIDEiP02489.

Protocols and materials databases

DNASUi1409.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291554; ENSP00000291554; ENSG00000160202.
GeneIDi102724652.
1409.
KEGGihsa:102724652.
hsa:1409.
UCSCiuc002zdd.3. human.

Organism-specific databases

CTDi1409.
DisGeNETi102724652.
1409.
GeneCardsiCRYAA.
HGNCiHGNC:2388. CRYAA.
HPAiCAB034116.
MalaCardsiCRYAA.
MIMi123580. gene.
604219. phenotype.
neXtProtiNX_P02489.
OpenTargetsiENSG00000160202.
ENSG00000276076.
Orphaneti1377. Cataract-microcornea syndrome.
98991. Nuclear cataract.
98995. Zonular cataract.
PharmGKBiPA26906.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3591. Eukaryota.
ENOG410YERS. LUCA.
GeneTreeiENSGT00760000119238.
HOGENOMiHOG000233954.
HOVERGENiHBG054766.
InParanoidiP02489.
KOiK09541.
OMAiGPKVQSG.
OrthoDBiEOG091G0USC.
PhylomeDBiP02489.
TreeFamiTF105049.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160202-MONOMER.

Miscellaneous databases

GeneWikiiCRYAA.
GenomeRNAii1409.
PROiP02489.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160202.
CleanExiHS_CRYAA.
ExpressionAtlasiP02489. baseline and differential.
GenevisibleiP02489. HS.

Family and domain databases

Gene3Di2.60.40.790. 1 hit.
InterProiIPR002068. A-crystallin/Hsp20_dom.
IPR001436. Alpha-crystallin/HSP.
IPR012274. Alpha-crystallin_A.
IPR003090. Alpha-crystallin_N.
IPR031107. HSP20.
IPR008978. HSP20-like_chaperone.
[Graphical view]
PANTHERiPTHR11527. PTHR11527. 1 hit.
PTHR11527:SF36. PTHR11527:SF36. 1 hit.
PfamiPF00525. Crystallin. 1 hit.
PF00011. HSP20. 1 hit.
[Graphical view]
PIRSFiPIRSF036514. Sm_HSP_B1. 1 hit.
PRINTSiPR00299. ACRYSTALLIN.
SUPFAMiSSF49764. SSF49764. 1 hit.
PROSITEiPS01031. HSP20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCRYAA_HUMAN
AccessioniPrimary (citable) accession number: P02489
Secondary accession number(s): Q53X53
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.