P07320 (CRGD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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	Cataract autosomal dominant (ADC) [MIM:604219]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.13 Ref.19 Cataract, congenital, non-nuclear polymorphic, autosomal dominant (CCP) [MIM:601286]: A congenital cataract characterized by a non-progressive phenotype and partial opacity that has a variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.18 Cataract, congenital, cerulean type, 3 (CCA3) [MIM:608983]: A cerulean form of autosomal dominant congenital cataract. Cerulean cataracts are characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.16 Cataract, crystalline aculeiform (CACA) [MIM:115700]: A congenital crystalline cataract characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. The opacity causes a variable degree of vision loss. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the beta/gamma-crystallin family. Contains 4 beta/gamma crystallin 'Greek key' domains.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Repeat
Molecular function	Eye lens protein
PTM	Oxidation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to reactive oxygen species Inferred from direct assay PubMed 8943244. Source: UniProtKB lens fiber cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB visual perception Inferred from mutant phenotype Ref.15Ref.16Ref.11. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	structural constituent of eye lens Non-traceable author statement Ref.9. 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 ADC; progressive punctate cataract with early onset; forms disulfide-linked oligomers. Ref.11 Ref.13

VAR_010733

Natural variant

24

1

P → S in CCP. Ref.18
Corresponds to variant rs28931605 [ dbSNP | Ensembl ].

VAR_034955

Natural variant

24

1

P → T in CCA3 and lamellar cataract; lowered solubility. Ref.6 Ref.15 Ref.16

VAR_021145

Natural variant

37

1

R → S in a patient with cataract; very low solubility; crystallizes spontaneously. Ref.12 Ref.14

VAR_010734

Natural variant

43

1

W → R in ADC; much less stable than the wild-type protein; more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation. Ref.19

VAR_064829

Natural variant

59

1

R → H in CACA; lowered solubility; crystallizes easily. Ref.8 Ref.10 Ref.14

VAR_010735

Natural variant

102

1

M → V. Ref.1 Ref.15

VAR_021146

Natural variant

107

1

E → A in CCP. Ref.17

VAR_034956

Experimental info

Mutagenesis

24 – 25

2

PN → TK: Wild-type solubility. Ref.6

Mutagenesis

24

1

P → S: Lowered solubility, but more soluble than T-24. Ref.6

Mutagenesis

24

1

P → TP: Wild-type solubility. Ref.6

Mutagenesis

24

1

P → V: Slightly lowered solubility. Ref.6

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 [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] [Europe PMC] [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] [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]. 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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-11.
[6]	"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] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PRO-24, CHARACTERIZATION OF VARIANT CCA3 THR-24.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF VARIANT HIS-59.
[9]	"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] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CACA HIS-59.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ADC CYS-15.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SER-37.
[13]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ADC CYS-15.
[14]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CATARACT SER-37 AND HIS-59.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LAMELLAR CATARACT THR-24, VARIANT VAL-102.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CCA3 THR-24.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CCP ALA-107.
[18]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CCP SER-24.
[19]	"A novel CRYGD mutation (p.Trp43Arg) causing autosomal dominant congenital cataract in a Chinese family." Wang B., Yu C., Xi Y.B., Cai H.C., Wang J., Zhou S., Zhou S., Wu Y., Yan Y.B., Ma X., Xie L. Hum. Mutat. 32:E1939-E1947(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ADC ARG-43, CHARACTERIZATION OF VARIANT ADC ARG-43.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_006891.3.

UniGene

Hs.546247.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2KFB	NMR	-	A	2-174	[»]
2KLJ	Other	-	A	2-174	[»]
4GR7	X-ray	1.70	A/X	2-174	[»]

ProteinModelPortal

P07320.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46208N.

STRING

9606.ENSP00000264376.

PTM databases

PhosphoSite

P07320.

Polymorphism databases

DMDM

2506321.

Proteomic databases

PaxDb

P07320.

PeptideAtlas

P07320.

PRIDE

P07320.

Protocols and materials databases

DNASU

1421.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264376; ENSP00000264376; ENSG00000118231.

GeneID

1421.

KEGG

hsa:1421.

UCSC

uc002vcn.4. human.

Organism-specific databases

CTD

1421.

GeneCards

GC02M208986.

HGNC

HGNC:2411. CRYGD.

MIM

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

neXtProt

NX_P07320.

Orphanet

98986. Cataract, Coppock-like.
1377. Cataract-microcornea syndrome.
98989. Cerulean cataract.
98990. Coralliform cataract.
98991. Nuclear cataract.
98995. Zonular cataract.

PharmGKB

PA26918.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309484.

HOGENOM

HOG000234389.

HOVERGEN

HBG003364.

InParanoid

P07320.

OMA

TGSHRIR.

OrthoDB

EOG4K9BD7.

PhylomeDB

P07320.

Gene expression databases

Bgee

P07320.

CleanEx

HS_CRYGD.

Genevestigator

P07320.

GermOnline

ENSG00000118231. 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

P07320.

GenomeRNAi

1421.

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:	May 1, 2013
This is version 148 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.