Reviewed, UniProtKB/Swiss-Prot P07320 (CRGD_HUMAN)

Names and origin

Protein names

Recommended name:
    Gamma-crystallin D
Alternative name(s):
    Gamma-D-crystallin
    Gamma-crystallin 4

Gene names

Name:	CRYGD
Synonyms:	CRYG4

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	174 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	Monomer By similarity.
Domain	Has a two-domain beta-structure, folded into four very similar Greek key motifs.
Involvement in disease	Defects in CRYGD are a cause of various types of autosomal dominant cataract [MIM:604219]. Cataracts are common major abnormalities of the eye that frequently cause blindness in infants. Defects in CRYGD are the cause of autosomal dominant non-nuclear polymorphic congenital cataract (PCC) [MIM:601286]; also known as polymorphic congenital cataract. PCC is characterized by a nonprogressive phenotype and partial opacity that has a variable location on the periphery between the fetal nucleus of the lens and the equator. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Ref.18 Ref.19 Defects in CRYGD are the cause of congenital cerulean cataract 3 (CCA3) [MIM:608983]; also known as congenital cataract blue dot type 3. CCA3 is a form of autosomal dominant congenital cataract (ADCC). Cerulean cataracts have peripheral bluish and white opacifications in concentric layers with occasional central lesions arranged radially. Although the opacities may be observed during fetal development and childhood, usually visual acuity is only mildly reduced until adulthood, when lens extraction is generally necessary. Ref.17 Defects in CRYGD are the cause of progressive punctate cataract [MIM:123690]. It is an autosomal dominant trait characterized by early postnatal onset. Ref.12 Ref.14 Defects in CRYGD are the cause of crystalline aculeiform cataract (CACA) [MIM:115700]. CACA is a congenital crystalline cataract characterized by fiberglass-like or needle-like crystals through or close to the axial regions of the lens. Ref.11
Sequence similarities	Belongs to the beta/gamma-crystallin family. Contains 4 beta/gamma crystallin 'Greek key' domains.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Eye lens protein
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Repeat
PTM	Oxidation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cellular response to reactive oxygen species Inferred from direct assay. Source: UniProtKB visual perception Ref.12 Ref.16 Ref.17 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	soluble fraction Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB structural constituent of eye lens Ref.10 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 174

173

Gamma-crystallin D

PRO_0000057588

Regions

Domain

2 – 40

39

Beta/gamma crystallin 'Greek key' 1

Domain

41 – 83

43

Beta/gamma crystallin 'Greek key' 2

Domain

88 – 128

41

Beta/gamma crystallin 'Greek key' 3

Domain

129 – 171

43

Beta/gamma crystallin 'Greek key' 4

Region

84 – 87

4

Connecting peptide

Sites

Site

46

1

Susceptible to oxidation

Natural variations

Natural variant

15

1

R → C in progressive punctate cataract; forms disulfide-linked oligomers. Ref.12 Ref.14

VAR_010733

Natural variant

24

1

P → S in PCC. dbSNP rs28931605. Ref.19

VAR_034955

Natural variant

24

1

P → T in CCA3 and lamellar cataract; lowered solubility.

VAR_021145

Natural variant

37

1

R → S in cataract; very low solubility; crystallizes spontaneously. Ref.13 Ref.15

VAR_010734

Natural variant

59

1

R → H in CACA; lowered solubility; crystallizes easily. Ref.11

VAR_010735

Natural variant

102

1

M → V Ref.1 Ref.16

VAR_021146

Natural variant

107

1

E → A in PCC. Ref.18

VAR_034956

Experimental info

Mutagenesis

24 – 25

2

PN → TK: Wild-type solubility. Ref.7

Mutagenesis

24

1

P → S: Lowered solubility, but more soluble than T-23. Ref.7

Mutagenesis

24

1

P → TP: Wild-type solubility. Ref.7

Mutagenesis

24

1

P → V: Slightly lowered solubility. Ref.7

Secondary structure

1

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174

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Helix

10 – 12

3

Beta strand

13 – 21

9

Turn

27 – 29

3

Beta strand

34 – 48

15

Turn

49 – 51

3

Beta strand

52 – 58

7

Beta strand

60 – 65

6

Helix

66 – 69

4

Beta strand

72 – 74

3

Beta strand

78 – 82

5

Beta strand

89 – 95

7

Helix

96 – 98

3

Beta strand

99 – 107

9

Helix

112 – 114

3

Beta strand

123 – 129

7

Beta strand

131 – 136

6

Turn

137 – 139

3

Beta strand

140 – 146

7

Beta strand

148 – 151

4

Helix

154 – 157

4

Beta strand

166 – 169

4

Sequences

	Sequence		Length	Mass (Da)
	P07320-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 437EC83FD79F12E4	FASTA	174	20,738
	10 20 30 40 50 60 MGKITLYEDR GFQGRHYECS SDHPNLQPYL SRCNSARVDS GCWMLYEQPN YSGLQYFLRR 70 80 90 100 110 120 GDYADHQQWM GLSDSVRSCR LIPHSGSHRI RLYEREDYRG QMIEFTEDCS CLQDRFRFNE 130 140 150 160 170 IHSLNVLEGS WVLYELSNYR GRQYLLMPGD YRRYQDWGAT NARVGSLRRV IDFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural and evolutionary relationships among five members of the human gamma-crystallin gene family." Meakin S.O., Breitman M.L., Tsui L.-C. Mol. Cell. Biol. 5:1408-1414(1985) [PubMed: 4033658] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-102.
[2]	"Cloning and expression of human lens crystallins." Petrash J.M., Mathur S., Manoharan M., Andley U.P. Invest. Ophthalmol. Vis. Sci. 36:S882-S882(1995) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"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 2-11.
[6]	"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: SUSCEPTIBILITY TO OXIDATION, MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin." Pande A., Annunziata O., Asherie N., Ogun O., Benedek G.B., Pande J. Biochemistry 44:2491-2500(2005) [PubMed: 15709761] [Abstract] Cited for: MUTAGENESIS OF PRO-24.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"High-resolution X-ray crystal structures of human gammaD crystallin (1.25 A) and the R58H mutant (1.15 A) associated with aculeiform cataract." Basak A., Bateman O., Slingsby C., Pande A., Asherie N., Ogun O., Benedek G.B., Pande J. J. Mol. Biol. 328:1137-1147(2003) [PubMed: 12729747] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF VARIANT HIS-59.
[10]	"Homology models of human gamma-crystallins: structural study of the extensive charge network in gamma-crystallins." Salim A., Zaidi Z.H. Biochem. Biophys. Res. Commun. 300:624-630(2003) [PubMed: 12507494] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[11]	"The gamma-crystallins and human cataracts: a puzzle made clearer." Heon E., Priston M., Schorderet D.F., Billingsley G.D., Girard P.O., Lubsen N., Munier F.L. Am. J. Hum. Genet. 65:1261-1267(1999) [PubMed: 10521291] [Abstract] Cited for: VARIANT CACA HIS-59.
[12]	"Progressive juvenile-onset punctate cataracts caused by mutation of the gamma-D-crystallin gene." Stephan D.A., Gillanders E., Vanderveen D., Freas-Lutz D., Wistow G., Baxevanis A.D., Robbins C.M., VanAuken A., Quesenberry M.I., Bailey-Wilson J., Juo S.-H.H., Trent J.M., Smith L., Brownstein M.J. Proc. Natl. Acad. Sci. U.S.A. 96:1008-1012(1999) [PubMed: 9927684] [Abstract] Cited for: VARIANT PROGRESSIVE PUNCTATE CATARACT CYS-15.
[13]	"Link between a novel human gamma-D-crystallin allele and a unique cataract phenotype explained by protein crystallography." Kmoch S., Brynda J., Asfaw B., Bezouska K., Novak P., Rezacova P., Ondrova L., Filipec M., Sedlacek J., Elleder M. Hum. Mol. Genet. 9:1779-1786(2000) [PubMed: 10915766] [Abstract] Cited for: VARIANT CATARACT SER-37.
[14]	"Molecular basis of a progressive juvenile-onset hereditary cataract." Pande A., Pande J., Asherie N., Lomakin A., Ogun O., King J.A., Lubsen N.H., Walton D., Benedek G.B. Proc. Natl. Acad. Sci. U.S.A. 97:1993-1998(2000) [PubMed: 10688888] [Abstract] Cited for: CHARACTERIZATION OF VARIANT PROGRESSIVE PUNCTATE CATARACT CYS-15.
[15]	"Crystal cataracts: human genetic cataract caused by protein crystallization." Pande A., Pande J., Asherie N., Lomakin A., Ogun O., King J., Benedek G.B. Proc. Natl. Acad. Sci. U.S.A. 98:6116-6120(2001) [PubMed: 11371638] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CATARACT SER-37 AND HIS-59.
[16]	"Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts." Santhiya S.T., Shyam Manohar M., Rawlley D., Vijayalakshmi P., Namperumalsamy P., Gopinath P.M., Loester J., Graw J. J. Med. Genet. 39:352-358(2002) [PubMed: 12011157] [Abstract] Cited for: VARIANT LAMELLAR CATARACT THR-24, VARIANT VAL-102.
[17]	"Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts." Nandrot E., Slingsby C., Basak A., Cherif-Chefchaouni M., Benazzouz B., Hajaji Y., Boutayeb S., Gribouval O., Arbogast L., Berraho A., Abitbol M., Hilal L. J. Med. Genet. 40:262-267(2003) [PubMed: 12676897] [Abstract] Cited for: VARIANT CCA3 THR-24.
[18]	"Two affected siblings with nuclear cataract associated with a novel missense mutation in the CRYGD gene." Messina-Baas O.M., Gonzalez-Huerta L.M., Cuevas-Covarrubias S.A. Mol. Vis. 12:995-1000(2006) [PubMed: 16943771] [Abstract] Cited for: VARIANT PCC ALA-107.
[19]	"Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state." Plotnikova O.V., Kondrashov F.A., Vlasov P.K., Grigorenko A.P., Ginter E.K., Rogaev E.I. Am. J. Hum. Genet. 81:32-43(2007) [PubMed: 17564961] [Abstract] Cited for: VARIANT PCC SER-24.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

K03006, K03005 Genomic DNA. Translation: AAA52112.1.
U66583 mRNA. Translation: AAB38686.1.
AC093698 Genomic DNA. Translation: AAY24041.1.
BC117338 mRNA. Translation: AAI17339.1.
BC117340 mRNA. Translation: AAI17341.1.

IPI

IPI00215881.

PIR

I77413.

RefSeq

NP_008822.2.

UniGene

Hs.546247

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H4A	X-ray	1.15	X	2-174	[»]
1HK0	X-ray	1.25	X	2-174	[»]
1LD0	model	-	A	1-174	[»]
2G98	X-ray	2.20	A/B	2-174	[»]

ModBase

Search...

PTM databases

PhosphoSite

P07320.

Proteomic databases

PeptideAtlas

P07320.

PRIDE

P07320.

Genome annotation databases

Ensembl

ENSG00000118231. Homo sapiens. [Contig view]

GeneID

1421.

KEGG

hsa:1421.

UCSC

uc002vcn.2. human.

Organism-specific databases

GeneCards

GC02M208694.

H-InvDB

HIX0030025.

HGNC

HGNC:2411. CRYGD.

MIM

115700. phenotype.
123690. gene+phenotype.
601286. phenotype.
604219. phenotype.
608983. phenotype.

Orphanet

98989. Cataract, cerulean.
98986. Cataract, Coppock-like.
91492. Non-syndromic congenital cataract.

PharmGKB

PA26918.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07320.

HOVERGEN

P07320.

OMA

P07320. IPHAGSH.

Gene expression databases

ArrayExpress

P07320.

Bgee

P07320.

CleanEx

HS_CRYGD.

GermOnline

ENSG00000118231. Homo sapiens.

Family and domain databases

InterPro

IPR001064. Crystallin.
[Graphical view]

Gene3D

G3DSA:2.60.20.10. Crystallin. 2 hits.

Pfam

PF00030. Crystall. 2 hits.
[Graphical view]

PRINTS

PR01367. BGCRYSTALLIN.

SMART

SM00247. XTALbg. 2 hits.
[Graphical view]

PROSITE

PS50915. CRYSTALLIN_BETA_GAMMA. 4 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5811.

SOURCE

Search...

Entry information

Entry name

CRGD_HUMAN

Accession

Primary (citable) accession number: P07320
Secondary accession number(s): Q17RF7, Q53R51, Q99681

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)