Reviewed, UniProtKB/Swiss-Prot P02489 (CRYAA_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-crystallin A chain
Alternative name(s):
    Heat shock protein beta-4
      Short name=HspB4
Cleaved into the following chain:
    1- Recommended name:
            Alpha-crystallin A chain, short form

Gene names

Name:	CRYAA
Synonyms:	CRYA1, HSPB4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	173 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May contribute to the transparency and refractive index of the lens.
Post-translational modification	O-glycosylated; contains N-acetylglucosamine side chains. Ref.9 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. 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. Ref.10 Ref.11 Ref.13 Ref.14 Ref.15
Involvement in disease	Defects in CRYAA are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an 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. Cataract is the most common treatable cause of visual disability in childhood.
Sequence similarities	Belongs to the small heat shock protein (HSP20) family.
Mass spectrometry	Molecular mass is 19950 Da from positions 1 - 173. Determined by ESI. Ref.10 Molecular mass is 19863 Da from positions 1 - 172. Determined by ESI. Ref.10 Molecular mass is 20029 Da from positions 1 - 173. Determined by ESI. With 1 phosphate group. Ref.10 Molecular mass is 19951 Da from positions 1 - 173. Determined by ESI. Ref.13 Molecular mass is 19864 Da from positions 1 - 172. Determined by ESI. Ref.13 Molecular mass is 19947 Da from positions 1 - 173. Determined by ESI. Ref.14 Molecular mass is 19851 Da from positions 1 - 172. Determined by ESI. Ref.14

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Eye lens protein
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
PTM	Acetylation Disulfide bond Glycoprotein Methylation Oxidation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: HGNC negative regulation of intracellular transport Inferred from direct assay. Source: HGNC protein homooligomerization Inferred from direct assay. Source: UniProtKB response to heat Inferred from electronic annotation. Source: InterPro visual perception Ref.16 Ref.18 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HGNC
Molecular function	structural constituent of eye lens Inferred from electronic annotation. Source: UniProtKB-KW unfolded protein binding Ref.3 Ref.21 Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 173	173	Alpha-crystallin A chain		PRO_0000125865
	Chain	1 – 172	172	Alpha-crystallin A chain, short form		PRO_0000226639
	Propeptide	173	1	Removed in short form		PRO_0000226640
Sites
	Site	18	1	Susceptible to oxidation
	Site	34	1	Susceptible to oxidation
	Site	138	1	Susceptible to oxidation
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine
	Modified residue	13	1	Phosphothreonine Ref.15
	Modified residue	21	1	Omega-N-methylated arginine Ref.15
	Modified residue	45	1	Phosphoserine Ref.15
	Modified residue	70	1	N6-acetyllysine Ref.13 Ref.15
	Modified residue	78	1	N6-acetyllysine Ref.15
	Modified residue	88	1	N6-acetyllysine; alternate Ref.15
	Modified residue	88	1	N6-methylated lysine; alternate Ref.15
	Modified residue	101	1	Deamidated asparagine; partial Ref.10 Ref.13 Ref.12
	Modified residue	122	1	Phosphoserine Ref.10 Ref.11 Ref.15
	Modified residue	140	1	Phosphothreonine Ref.15
	Modified residue	145	1	N6-acetyllysine Ref.15
	Glycosylation	162	1	O-linked (GlcNAc) By similarity
	Disulfide bond	131 ↔ 142		Ref.10
Natural variations
	Natural variant	21	1	R → L in congenital cataract; associated with macular hypoplasia and a generally hypopigmented fundus. Ref.19		VAR_046892
	Natural variant	49	1	R → C in ADC; nuclear cataract.		VAR_038375
	Natural variant	105	1	D → H in a breast cancer sample; somatic mutation. Ref.20		VAR_036564
	Natural variant	116	1	R → C in ADC; zonular central nuclear cataract; reduced chaperone-like activity and increased membrane-binding capacity.		VAR_003819
	Natural variant	116	1	R → H in ADC; 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.		VAR_046893
Experimental info
	Sequence conflict	45	1	S → T in AAA52105. Ref.7
	Sequence conflict	153 – 155	3	THA → HT Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P02489-1 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 81804A8439837D50	FASTA	173	19,909
	10 20 30 40 50 60 MDVTIQHPWF KRTLGPFYPS RLFDQFFGEG LFEYDLLPFL SSTISPYYRQ SLFRTVLDSG 70 80 90 100 110 120 ISEVRSDRDK FVIFLDVKHF SPEDLTVKVQ DDFVEIHGKH NERQDDHGYI SREFHRRYRL 130 140 150 160 170 PSNVDQSALS CSLSADGMLT FCGPKIQTGL DATHAERAIP VSREEKPTSA PSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The amino acid sequence of the A chain of human alpha-crystallin." de Jong W.W., Terwindt E.C., Bloemendal H. FEBS Lett. 58:310-313(1975) [PubMed: 817940] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE.
[2]	"A reassessment of mammalian alpha A-crystallin sequences using DNA sequencing: implications for anthropoid affinities of tarsier." Jaworski C.J. J. Mol. Evol. 41:901-908(1995) [PubMed: 8587135] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens.
[3]	"Cloning, expression, and chaperone-like activity of human alphaA-crystallin." Andley U.P., Mathur S., Griest T.A., Petrash J.M. J. Biol. Chem. 271:31973-31980(1996) [PubMed: 8943244] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens.
[4]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"A pseudo-exon in the functional human alpha A-crystallin gene." Jaworski C.J., Piatigorsky J. Nature 337:752-754(1989) [PubMed: 2918909] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104.
[7]	"Isolation and partial characterization of the human alpha A-crystallin gene." McDevitt D.S., Hawkins J.W., Jaworski C.J., Piatigorsky J. Exp. Eye Res. 43:285-291(1986) [PubMed: 3758227] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63 AND 166-173. Tissue: Spleen.
[8]	"Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the identification of the major proteins in young human lens." Lampi K.J., Ma Z., Shih M., Shearer T.R., Smith J.B., Smith D.L., David L.L. J. Biol. Chem. 272:2268-2275(1997) [PubMed: 8999933] [Abstract] Cited for: PROTEIN SEQUENCE OF 13-21 AND 79-88.
[9]	"Vertebrate lens alpha-crystallins are modified by O-linked N-acetylglucosamine." Roquemore E.P., Dell A., Morris H.R., Panico M., Reason A.J., Savoy L.-A., Wistow G.J., Zigler J.S. Jr., Earles B.J., Hart G.W. J. Biol. Chem. 267:555-563(1992) [PubMed: 1730617] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATE.
[10]	"Post-translational modifications of water-soluble human lens crystallins from young adults." Miesbauer L.R., Zhou X., Yang Z., Yang Z., Sun Y., Smith D.L., Smith J.B. J. Biol. Chem. 269:12494-12502(1994) [PubMed: 8175657] [Abstract] Cited for: PHOSPHORYLATION AT SER-122, DISULFIDE BOND, PROTEOLYTIC PROCESSING OF C-TERMINAL, DEAMIDATION AT ASN-101, MASS SPECTROMETRY.
[11]	"Differential phosphorylation of alpha-A crystallin in human lens of different age." Takemoto L.J. Exp. Eye Res. 62:499-504(1996) [PubMed: 8759518] [Abstract] Cited for: PHOSPHORYLATION AT SER-122.
[12]	"Quantitation of asparagine-101 deamidation from alpha-A crystallin during aging of the human lens." Takemoto L.J. Curr. Eye Res. 17:247-250(1998) [PubMed: 9543632] [Abstract] Cited for: DEAMIDATION AT ASN-101.
[13]	"In vivo acetylation identified at lysine 70 of human lens alphaA-crystallin." Lin P.P., Barry R.C., Smith D.L., Smith J.B. Protein Sci. 7:1451-1457(1998) [PubMed: 9655350] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF C-TERMINAL, ACETYLATION AT LYS-70, PHOSPHORYLATION, DEAMIDATION AT ASN-101, MASS SPECTROMETRY.
[14]	"The major in vivo modifications of the human water-insoluble lens crystallins are disulfide bonds, deamidation, methionine oxidation and backbone cleavage." Hanson S.R.A., Hasan A., Smith D.L., Smith J.B. Exp. Eye Res. 71:195-207(2000) [PubMed: 10930324] [Abstract] Cited for: PHOSPHORYLATION, SUSCEPTIBILITY TO OXIDATION, PROTEOLYTIC PROCESSING OF C-TERMINAL, MASS SPECTROMETRY.
[15]	"Shotgun identification of protein modifications from protein complexes and lens tissue." MacCoss M.J., McDonald W.H., Saraf A., Sadygov R., Clark J.M., Tasto J.J., Gould K.L., Wolters D., Washburn M., Weiss A., Clark J.I., Yates J.R. III Proc. Natl. Acad. Sci. U.S.A. 99:7900-7905(2002) [PubMed: 12060738] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-13; SER-45; SER-122 AND THR-140, ACETYLATION AT LYS-70; LYS-78; LYS-88 AND LYS-145, METHYLATION AT ARG-21 AND LYS-88, SUSCEPTIBILITY TO OXIDATION, MASS SPECTROMETRY.
[16]	"Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA." Litt M., Kramer P., la Morticella D.M., Murphey W., Lovrien E.W., Weleber R.G. Hum. Mol. Genet. 7:471-474(1998) [PubMed: 9467006] [Abstract] Cited for: VARIANT ADC CYS-116.
[17]	"Structural and functional changes in the alpha A-crystallin R116C mutant in hereditary cataracts." Cobb B.A., Petrash J.M. Biochemistry 39:15791-15798(2000) [PubMed: 11123904] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ADC CYS-116.
[18]	"Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q." Mackay D.S., Andley U.P., Shiels A. Eur. J. Hum. Genet. 11:784-793(2003) [PubMed: 14512969] [Abstract] Cited for: VARIANT ADC CYS-49.
[19]	"Congenital cataract and macular hypoplasia in humans associated with a de novo mutation in CRYAA and compound heterozygous mutations in P." Graw J., Klopp N., Illig T., Preising M.N., Lorenz B. Graefes Arch. Clin. Exp. Ophthalmol. 244:912-919(2006) [PubMed: 16453125] [Abstract] Cited for: VARIANT CONGENITAL CATARACT LEU-21.
[20]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-105.
[21]	"A novel mutation in AlphaA-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family." Gu F., Luo W., Li X., Wang Z., Lu S., Zhang M., Zhao B., Zhu S., Feng S., Yan Y.-B., Huang S., Ma X. Hum. Mutat. 29:769-769(2008) [PubMed: 18407550] [Abstract] Cited for: VARIANT ADC HIS-116, CHARACTERIZATION OF VARIANT ADC HIS-116.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U05569 mRNA. Translation: AAA97523.1. U66584 mRNA. Translation: AAC50900.1. X14789 mRNA. Translation: CAA32891.1. BC069528 mRNA. Translation: AAH69528.1. M35628 Genomic DNA. Translation: AAA52106.1. M35629 Genomic DNA. Translation: AAA52105.1. AP001748 Genomic DNA. Translation: BAA95535.1.
IPI	IPI00021062.
PIR	CYHUAA. S03344.
RefSeq	NP_000385.1.
UniGene	Hs.184085
3D structure databases
SMR	P02489. Positions 66-148.
DisProt	DP00444.
ModBase	Search...
Protein-protein interaction databases
STRING	P02489.
PTM databases
GlycoSuiteDB	P02489.
PhosphoSite	P02489.
2-D gel databases
SWISS-2DPAGE	P02489.
Proteomic databases
PeptideAtlas	P02489.
PRIDE	P02489.
Genome annotation databases
Ensembl	ENST00000291554; ENSP00000291554; ENSG00000160202; Homo sapiens. [Genome view]
GeneID	1409.
KEGG	hsa:1409.
UCSC	uc002zdd.1. human.
Organism-specific databases
CTD	1409.
GeneCards	GC21P043462.
H-InvDB	HIX0040917.
HGNC	HGNC:2388. CRYAA.
MIM	123580. gene+phenotype. 604219. phenotype.
Orphanet	98991. Cataract, nuclear. 98995. Cataract, zonular. 91492. Non-syndromic congenital cataract.
PharmGKB	PA26906.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG20855.
HOGENOM	HBG748242.
HOVERGEN	P02489.
InParanoid	P02489.
OMA	DITIQHP.
OrthoDB	EOG966Z58.
PhylomeDB	P02489.
Gene expression databases
ArrayExpress	P02489.
Bgee	P02489.
CleanEx	HS_CRYAA.
Genevestigator	P02489.
GermOnline	ENSG00000160202. Homo sapiens.
Family and domain databases
InterPro	IPR001436. Alpha-crystallin/HSP. IPR012274. Alpha-crystallin_A. IPR003090. Alpha-crystallin_N. IPR002068. Hsp20. IPR008978. HSP20-like_chaperone. [Graphical view]
PANTHER	PTHR11527:SF36. A-crystallin_A. 1 hit.
Pfam	PF00525. Crystallin. 1 hit. PF00011. HSP20. 1 hit. [Graphical view]
PRINTS	PR00299. ACRYSTALLIN.
PROSITE	PS01031. HSP20. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	5761.
SOURCE	Search...

Entry information

Entry name

CRYAA_HUMAN

Accession

Primary (citable) accession number: P02489

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	October 1, 1996
Last modified:	February 9, 2010
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.