Reviewed, UniProtKB/Swiss-Prot P02511 (CRYAB_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-crystallin B chain
Alternative name(s):
    Alpha(B)-crystallin
    Rosenthal fiber component
    Heat shock protein beta-5
      Short name=HspB5
    Renal carcinoma antigen NY-REN-27

Gene names

Name:	CRYAB
Synonyms:	CRYA2

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	175 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May contribute to the transparency and refractive index of the lens.
Subunit structure	Homodimer. Aggregates with homologous proteins, including CRYAA and the small heat shock protein HSPB1, to form large heteromeric complexes. Interacts with HSPBAP1 and TTN/titin. Ref.14 Ref.18 Ref.23
Tissue specificity	Lens as well as other tissues.
Involvement in disease	Seen as Rosenthal fiber protein in the brain tissue of patients with Alexander disease. Defects in CRYAB are the cause of alpha-B crystallinopathy [MIM:608810]. Alpha-B crystallinopathy is a an autosomal dominant form of desmin-related myopathy (DRM) that results in weakness of the proximal and distal limb muscle (including neck, velopharynx, and trunk muscles), signs of cardiomyopathy and cataract. Patients with progressive myopathy characterized by myofibrillar degeneration that commences at the Z-disk, have been described. Mutations truncate the essential C-terminal domain of the protein required for the chaperone function. Crystallins do not turn over as the lens ages, providing ample opportunity for post-translational modifications or oxidations. These modifications may change crystallin solubility properties and favor senile cataract.
Sequence similarities	Belongs to the small heat shock protein (HSP20) family.
Mass spectrometry	Molecular mass is 20201 Da from positions 1 - 175. Determined by ESI. Ref.15 Molecular mass is 20281 Da from positions 1 - 175. Determined by ESI. With 1 phosphate group. Ref.15 Molecular mass is 20360 Da from positions 1 - 175. Determined by ESI. With 2 phosphate groups. Ref.15 Molecular mass is 20199 Da from positions 1 - 175. Determined by ESI. Ref.17 Molecular mass is 20278 Da from positions 1 - 175. Determined by ESI. With 1 phosphate group. Ref.17

Ontologies

Keywords
Cellular component	Eye lens protein
Coding sequence diversity	Polymorphism
Disease	Cataract Desmin-related myopathy Disease mutation
PTM	Acetylation Glycoprotein Methylation Oxidation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: HGNC muscle contraction Ref.24 Traceable author statement. Source: ProtInc negative regulation of intracellular transport Inferred from direct assay. Source: HGNC protein folding Ref.24 Non-traceable author statement. Source: ProtInc protein homooligomerization Inferred from direct assay. Source: UniProtKB response to heat Inferred from electronic annotation. Source: InterPro
Molecular function	structural constituent of eye lens Inferred from electronic annotation. Source: UniProtKB-KW unfolded protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSPB8	Q9UJY1	1	EBI-739060,EBI-739074

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 175	175	Alpha-crystallin B chain		PRO_0000125907
Sites
	Site	48	1	Susceptible to oxidation
	Site	60	1	Susceptible to oxidation
	Site	68	1	Susceptible to oxidation
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Probable Ref.14
	Modified residue	19	1	Phosphoserine Ref.15 Ref.21
	Modified residue	21	1	Phosphoserine Ref.21
	Modified residue	22	1	Omega-N-methylated arginine Ref.21
	Modified residue	43	1	Phosphoserine Ref.21
	Modified residue	45	1	Phosphoserine Ref.15 Ref.21 Ref.19
	Modified residue	50	1	Omega-N-methylated arginine Ref.21
	Modified residue	53	1	Phosphoserine Ref.21
	Modified residue	59	1	Phosphoserine Ref.15 Ref.21 Ref.19
	Modified residue	76	1	Phosphoserine Ref.21
	Modified residue	92	1	N6-acetyllysine; partial Ref.21 Ref.20
	Glycosylation	170	1	O-linked (GlcNAc) By similarity
Natural variations
	Natural variant	41	1	S → Y: dbSNP rs2234703.		VAR_014607
	Natural variant	51	1	P → L: dbSNP rs2234704.		VAR_014608
	Natural variant	120	1	R → G in alpha-B crystallinopathy; decreased interactions with wild-type CRYAA and CRYAB but increased interactions with wild-type CRYBB2 and CRYGC. Ref.24 Ref.25		VAR_007899
Experimental info
	Sequence conflict	165	1	E → K in AAC19161. Ref.4
	Sequence conflict	175	1	K → KKMPFLELHFLKQESFPTSE in AAC19161. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P02511-1 [UniParc]. Last modified January 1, 1990. Version 2. Checksum: AE08BED46B7849CB	FASTA	175	20,159
	10 20 30 40 50 60 MDIAIHHPWI RRPFFPFHSP SRLFDQFFGE HLLESDLFPT STSLSPFYLR PPSFLRAPSW 70 80 90 100 110 120 FDTGLSEMRL EKDRFSVNLD VKHFSPEELK VKVLGDVIEV HGKHEERQDE HGFISREFHR 130 140 150 160 170 KYRIPADVDP LTITSSLSSD GVLTVNGPRK QVSGPERTIP ITREEKPAVT AAPKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structure of the B2 chain of human alpha-crystallin." Kramps J.A., de Man B.M., de Jong W.W. FEBS Lett. 74:82-84(1977) [PubMed: 838078] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE.
[2]	"Human alpha B-crystallin gene and preferential promoter function in lens." Dubin R.A., Ally A.H., Chung S., Piatigorsky J. Genomics 7:594-601(1990) [PubMed: 2387586] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Accumulation of alpha B-crystallin in brains of patients with Alexander's disease is not due to an abnormality of the 5'-flanking and coding sequence of the genomic DNA." Iwaki A., Iwaki T., Goldman J.E., Ogomori K., Tateishi J., Sakaki Y. Neurosci. Lett. 140:89-92(1992) [PubMed: 1407707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	Yu W., Sarginson J., Gibbs R.A. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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]. Tissue: Heart.
[10]	"Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle." Kato K., Shinohara H., Goto S., Inaguma Y., Morishita R., Asano T. J. Biol. Chem. 267:7718-7725(1992) [PubMed: 1560006] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-24; 35-66 AND 118-175, ASSOCIATION WITH HSPB1. Tissue: Pectoralis muscle.
[11]	"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 57-66.
[12]	"The major protein expression profile and two-dimensional protein database of human heart." Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A., Ershova E.S., Egorov T.A., Musalyamov A.K. Electrophoresis 16:1160-1169(1995) [PubMed: 7498159] [Abstract] Cited for: PROTEIN SEQUENCE OF 83-89 AND 164-172. Tissue: Heart.
[13]	"Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain." Iwaki T., Kume-Iwaki A., Liem R.K.H., Goldman J.E. Cell 57:71-78(1989) [PubMed: 2539261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 107-175.
[14]	"Simultaneous racemization and isomerization at specific aspartic acid residues in alpha B-crystallin from the aged human lens." Fujii N., Ishibashi Y., Satoh K., Fujino M., Harada K. Biochim. Biophys. Acta 1204:157-163(1994) [PubMed: 8142454] [Abstract] Cited for: RACEMIZATION/ISOMERIZATION OF SPECIFIC ASP.
[15]	"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-19; SER-45 AND SER-59, MASS SPECTROMETRY.
[16]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[17]	"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: MASS SPECTROMETRY, SUSCEPTIBILITY TO OXIDATION, PHOSPHORYLATION.
[18]	"Identification and characterization of a novel protein from Sertoli cells, PASS1, that associates with mammalian small stress protein hsp27." Liu C., Gilmont R.R., Benndorf R., Welsh M.J. J. Biol. Chem. 275:18724-18731(2000) [PubMed: 10751411] [Abstract] Cited for: INTERACTION WITH HSPBAP1.
[19]	"Ser-59 is the major phosphorylation site in alphaB-crystallin accumulated in the brains of patients with Alexander's disease." Kato K., Inaguma Y., Ito H., Iida K., Iwamoto I., Kamei K., Ochi N., Ohta H., Kishikawa M. J. Neurochem. 76:730-736(2001) [PubMed: 11158243] [Abstract] Cited for: PHOSPHORYLATION AT SER-45 AND SER-59.
[20]	"In vivo carbamylation and acetylation of water-soluble human lens alphaB-crystallin lysine 92." Lapko V.N., Smith D.L., Smith J.B. Protein Sci. 10:1130-1136(2001) [PubMed: 11369851] [Abstract] Cited for: ACETYLATION AT LYS-92.
[21]	"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 SER-19; SER-21; SER-43; SER-45; SER-53; SER-59 AND SER-76, METHYLATION AT ARG-22 AND ARG-50, ACETYLATION AT LYS-92, SUSCEPTIBILITY TO OXIDATION, MASS SPECTROMETRY.
[22]	"Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations." Selcen D., Engel A.G. Ann. Neurol. 54:804-810(2003) [PubMed: 14681890] [Abstract] Cited for: INVOLVEMENT IN ALPHA-B CRYSTALLINOPATHY.
[23]	"Association of the chaperone alphaB-crystallin with titin in heart muscle." Bullard B., Ferguson C., Minajeva A., Leake M.C., Gautel M., Labeit D., Ding L., Labeit S., Horwitz J., Leonard K.R., Linke W.A. J. Biol. Chem. 279:7917-7924(2004) [PubMed: 14676215] [Abstract] Cited for: INTERACTION WITH TTN.
[24]	"A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy." Vicart P., Caron A., Guicheney P., Li Z., Prevost M.-C., Faure A., Chateau D., Chapon F., Tome F., Dupret J.-M., Paulin D., Fardeau M. Nat. Genet. 20:92-95(1998) [PubMed: 9731540] [Abstract] Cited for: VARIANT ALPHA-B CRYSTALLINOPATHY GLY-120.
[25]	"Alteration of protein-protein interactions of congenital cataract crystallin mutants." Fu L., Liang J.J.-N. Invest. Ophthalmol. Vis. Sci. 44:1155-1159(2003) [PubMed: 12601044] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ALPHA-B CRYSTALLINOPATHY GLY-120.
[26]	"Crystal structures of alpha-crystallin domain dimers of alphaB-crystallin and Hsp20." Bagneris C., Bateman O.A., Naylor C.E., Cronin N., Boelens W.C., Keep N.H., Slingsby C. J. Mol. Biol. 392:1242-1252(2009) [PubMed: 19646995] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 67-157, HOMODIMER.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M28638 Genomic DNA. Translation: AAA52104.1.
S45630 mRNA. Translation: AAB23453.1.
AF007162 mRNA. Translation: AAC19161.1.
AK314029 mRNA. Translation: BAG36739.1.
BT006770 mRNA. Translation: AAP35416.1.
EF444955 Genomic DNA. Translation: ACA05949.1.
CH471065 Genomic DNA. Translation: EAW67162.1.
BC007008 mRNA. Translation: AAH07008.1.
M24906 mRNA. Translation: AAA60267.1.

IPI

IPI00021369.

PIR

CYHUAB. A35332.

RefSeq

NP_001876.1.

UniGene

Hs.408767

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WJ7	X-ray	2.63	A/B/C/D/E	67-157	[»]

DisProt

DP00445.

ModBase

Search...

Protein-protein interaction databases

IntAct

P02511. 2 interactions.

STRING

P02511.

PTM databases

GlycoSuiteDB

P02511.

PhosphoSite

P02511.

2-D gel databases

SWISS-2DPAGE

P02511.

HSC-2DPAGE

P02511.

REPRODUCTION-2DPAGE

IPI00021369.

Proteomic databases

PRIDE

P02511.

Genome annotation databases

Ensembl

ENST00000227251; ENSP00000227251; ENSG00000109846; Homo sapiens. [Genome view]

GeneID

1410.

KEGG

hsa:1410.

UCSC

uc001pmf.1. human.

Organism-specific databases

CTD

1410.

GeneCards

GC11M111284.

H-InvDB

HIX0010115.

HGNC

HGNC:2389. CRYAB.

HPA

CAB002053.

MIM

123590. gene+phenotype.
608810. phenotype.

Orphanet

98910. Alpha-cristallinopathy.
98993. Cataract, posterior polar.
98995. Cataract, zonular.
91492. Non-syndromic congenital cataract.

PharmGKB

PA26907.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P02511.

HOVERGEN

P02511.

OMA

DRYVIYL.

Gene expression databases

ArrayExpress

P02511.

Bgee

P02511.

CleanEx

HS_CRYAB.

Genevestigator

P02511.

GermOnline

ENSG00000109846. Homo sapiens.

Family and domain databases

InterPro

IPR001436. Alpha-crystallin/HSP.
IPR012273. Alpha-crystallin_B.
IPR003090. Alpha-crystallin_N.
IPR002068. Hsp20.
[Graphical view]

PANTHER

PTHR11527:SF37. A-crystallin_B. 1 hit.

Pfam

PF00525. Crystallin. 1 hit.
PF00011. HSP20. 1 hit.
[Graphical view]

PRINTS

PR00299. ACRYSTALLIN.

ProDom

PD001193. Crystallin_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS01031. HSP20. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5765.

PMAP-CutDB

P02511.

SOURCE

Search...

Entry information

Entry name

CRYAB_HUMAN

Accession

Primary (citable) accession number: P02511
Secondary accession number(s): B0YIX0 , O43416, Q9UC37, Q9UC38, Q9UC39, Q9UC40, Q9UC41

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 1, 1990
Last modified:	November 3, 2009
This is version 121 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.