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Protein

Alpha-crystallin A chain

Gene

CRYAA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: HGNC
  • negative regulation of intracellular transport Source: HGNC
  • protein homooligomerization Source: UniProtKB
  • protein stabilization Source: CAFA
  • response to stimulus Source: UniProtKB-KW
  • visual perception Source: UniProtKB

Keywordsi

Molecular functionChaperone, Eye lens protein
Biological processSensory transduction, Vision
LigandMetal-binding, Zinc

Enzyme and pathway databases

SIGNORiP02489

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

EuPathDBiHostDB:ENSG00000160202.7
HGNCiHGNC:2388 CRYAA
MIMi123580 gene
neXtProtiNX_P02489

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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.1 Publication
Cataract 9, multiple types (CTRCT9)7 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 dbSNP:rs397515624EnsemblClinVar.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 dbSNP:rs74315441EnsemblClinVar.1
Natural variantiVAR_003819116R → C in CTRCT9; zonular central nuclear cataract; reduced chaperone-like activity and increased membrane-binding capacity. 2 PublicationsCorresponds to variant dbSNP:rs74315439EnsemblClinVar.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 dbSNP:rs121912973EnsemblClinVar.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
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) serineBy 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 approximately 50% of the lens molecules.5 Publications

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Oxidation, Phosphoprotein

Proteomic databases

PaxDbiP02489
PeptideAtlasiP02489
PRIDEiP02489

2D gel databases

SWISS-2DPAGEiP02489

PTM databases

GlyConnecti33
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

HPAiHPA037737

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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi107799, 68 interactors
DIPiDIP-41265N
IntActiP02489, 10 interactors
MINTiP02489
STRINGi9606.ENSP00000291554

Structurei

3D structure databases

ProteinModelPortaliP02489
SMRiP02489
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini52 – 164sHSPPROSITE-ProRule annotationAdd BLAST113

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
OMAiGERQDDH
OrthoDBiEOG091G0USC
PhylomeDBiP02489
TreeFamiTF105049

Family and domain databases

Gene3Di2.60.40.790, 1 hit
InterProiView protein in InterPro
IPR002068 A-crystallin/Hsp20_dom
IPR001436 Alpha-crystallin/HSP
IPR012274 Alpha-crystallin_A
IPR003090 Alpha-crystallin_N
IPR031107 HSP20
IPR008978 HSP20-like_chaperone
PANTHERiPTHR11527 PTHR11527, 1 hit
PTHR11527:SF36 PTHR11527:SF36, 1 hit
PfamiView protein in Pfam
PF00525 Crystallin, 1 hit
PF00011 HSP20, 1 hit
PIRSFiPIRSF036514 Sm_HSP_B1, 1 hit
PRINTSiPR00299 ACRYSTALLIN
SUPFAMiSSF49764 SSF49764, 1 hit
PROSITEiView protein in PROSITE
PS01031 SHSP, 1 hit

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 dbSNP:rs397515624EnsemblClinVar.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 dbSNP:rs74315441EnsemblClinVar.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 dbSNP:rs74315439EnsemblClinVar.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 dbSNP:rs121912973EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiCRYAA_HUMAN
AccessioniPrimary (citable) accession number: P02489
Secondary accession number(s): Q53X53
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 196 of the entry and version 2 of the sequence. See 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

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