P53673 (CRBA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-crystallin A4

Alternative name(s):
Beta-A4 crystallin

Gene names

Name:

CRYBA4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	196 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	Crystallins are the dominant structural components of the vertebrate eye lens.
Subunit structure	Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms By similarity.
Domain	Has a two-domain beta-structure, folded into four very similar Greek key motifs.
Involvement in disease	Cataract, zonular 2 (CZ2) [MIM:610425]: A form of zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Microphthalmia, isolated, with cataract, 4 (MCOPCT4) [MIM:610426]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataract and other abnormalities like cataract may also be present. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the beta/gamma-crystallin family. Contains 4 beta/gamma crystallin 'Greek key' domains.
Mass spectrometry	Molecular mass is 22285±3 Da from positions 2 - 196. Determined by ESI. Ref.1
Sequence caution	The sequence CAG30310.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation Microphthalmia
Domain	Repeat
Molecular function	Eye lens protein
PTM	Acetylation Oxidation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	camera-type eye development Inferred from mutant phenotype Ref.6. Source: UniProtKB visual perception Inferred from mutant phenotype Ref.6. Source: UniProtKB
Molecular_function	structural constituent of eye lens Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 196

195

Beta-crystallin A4

PRO_0000057545

Regions

Domain

12 – 51

40

Beta/gamma crystallin 'Greek key' 1

Domain

52 – 98

47

Beta/gamma crystallin 'Greek key' 2

Domain

105 – 146

42

Beta/gamma crystallin 'Greek key' 3

Domain

147 – 195

49

Beta/gamma crystallin 'Greek key' 4

Region

2 – 11

10

N-terminal arm

Region

99 – 104

6

Connecting peptide

Sites

Site

149

1

Susceptible to oxidation

Amino acid modifications

Modified residue

2

1

N-acetylthreonine

Natural variations

Natural variant

36

1

V → M.
Corresponds to variant rs35520672 [ dbSNP | Ensembl ].

VAR_033824

Natural variant

69

1

L → P in MCOPCT4; is predicted to disrupt the beta-sheet structure of the protein. Ref.6

VAR_029528

Natural variant

84

1

T → M.
Corresponds to variant rs4277 [ dbSNP | Ensembl ].

VAR_014903

Natural variant

94

1

F → S in CZ2; modeling suggests that this substitution would significantly reduce the intrinsic stability of the crystalline monomer. Ref.6

VAR_029529

Secondary structure

1

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196

Helix Strand Turn

Details...

Beta strand

13 – 19

7

Helix

20 – 22

3

Beta strand

23 – 31

9

Helix

36 – 39

4

Beta strand

46 – 52

7

Beta strand

54 – 59

6

Helix

60 – 62

3

Beta strand

63 – 69

7

Beta strand

71 – 74

4

Helix

78 – 81

4

Beta strand

93 – 96

4

Helix

102 – 104

3

Beta strand

106 – 113

8

Beta strand

119 – 124

6

Helix

130 – 132

3

Beta strand

136 – 138

3

Beta strand

141 – 154

14

Turn

155 – 157

3

Beta strand

158 – 165

8

Helix

169 – 171

3

Turn

176 – 178

3

Beta strand

190 – 193

4

Sequences

	Sequence		Length	Mass (Da)
	P53673 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 104EC68E3CDE5740	FASTA	196	22,374
	10 20 30 40 50 60 MTLQCTKSAG PWKMVVWDED GFQGRRHEFT AECPSVLELG FETVRSLKVL SGAWVGFEHA 70 80 90 100 110 120 GFQGQQYILE RGEYPSWDAW GGNTAYPAER LTSFRPAACA NHRDSRLTIF EQENFLGKKG 130 140 150 160 170 180 ELSDDYPSLQ AMGWEGNEVG SFHVHSGAWV CSQFPGYRGF QYVLECDHHS GDYKHFREWG 190 SHAPTFQVQS IRRIQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 14-25; 159-174 AND 178-192, MASS SPECTROMETRY.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Regional fine mapping of the beta crystallin genes on chromosome 22 excludes these genes as physically linked markers for neurofibromatosis type 2." Bijlsma E.K., Delattre O., Juyn J.A., Melot T., Westerveld A., Dumanski J.P., Thomas G., Hulsebos T.J.M. Genes Chromosomes Cancer 8:112-118(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-194.
[6]	"CRYBA4, a novel human cataract gene, is also involved in microphthalmia." Billingsley G., Santhiya S.T., Paterson A.D., Ogata K., Wodak S., Hosseini S.M., Manisastry S.M., Vijayalakshmi P., Gopinath P.M., Graw J., Heon E. Am. J. Hum. Genet. 79:702-709(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MCOPCT4 PRO-69, VARIANT CZ2 SER-94.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U59057 mRNA. Translation: AAC50970.1.
CR456424 mRNA. Translation: CAG30310.1. Different initiation.
Z95115 Genomic DNA. Translation: CAI17980.2.
BC069404 mRNA. Translation: AAH69404.1.
BC096171 mRNA. Translation: AAH96171.1.
BC096172 mRNA. Translation: AAH96172.1.
BC096173 mRNA. Translation: AAH96173.1.
BC096174 mRNA. Translation: AAH96174.1.
S67583 Genomic DNA. Translation: AAD13994.1.

IPI

IPI00878361.

PIR

I54083.

RefSeq

NP_001877.1. NM_001886.2.

UniGene

Hs.57690.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LWK	X-ray	1.70	A	8-196	[»]

ProteinModelPortal

P53673.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-5161963.

STRING

9606.ENSP00000346805.

PTM databases

PhosphoSite

P53673.

Polymorphism databases

DMDM

2506318.

Proteomic databases

PaxDb

P53673.

PRIDE

P53673.

Protocols and materials databases

DNASU

1413.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354760; ENSP00000346805; ENSG00000196431.

GeneID

1413.

KEGG

hsa:1413.

UCSC

uc003acz.4. human.

Organism-specific databases

CTD

1413.

GeneCards

GC22P027017.

HGNC

HGNC:2396. CRYBA4.

MIM

123631. gene.
610425. phenotype.
610426. phenotype.

neXtProt

NX_P53673.

Orphanet

1377. Cataract-microcornea syndrome.
2543. Microphthalmia - cataract.
98995. Zonular cataract.

PharmGKB

PA26910.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39249.

HOGENOM

HOG000234388.

HOVERGEN

HBG003364.

InParanoid

P53673.

OMA

FHVHSGA.

OrthoDB

EOG48D0W7.

Gene expression databases

Bgee

P53673.

CleanEx

HS_CRYBA4.

Genevestigator

P53673.

GermOnline

ENSG00000196431. Homo sapiens.

Family and domain databases

InterPro

IPR001064. Beta/gamma_crystallin.
IPR011024. G_crystallin-rel.
[Graphical view]

Pfam

PF00030. Crystall. 2 hits.
[Graphical view]

PRINTS

PR01367. BGCRYSTALLIN.

SMART

SM00247. XTALbg. 2 hits.
[Graphical view]

SUPFAM

SSF49695. G_crystallin_SF. 1 hit.

PROSITE

PS50915. CRYSTALLIN_BETA_GAMMA. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P53673.

GenomeRNAi

1413.

NextBio

5781.

SOURCE

Search...

Entry information

Entry name

CRBA4_HUMAN

Accession

Primary (citable) accession number: P53673
Secondary accession number(s): Q4VB22, Q6ICE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.