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P07320 (CRGD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-crystallin D
Alternative name(s):
Gamma-D-crystallin
Gamma-crystallin 4
Gene names
Name:CRYGD
Synonyms:CRYG4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length174 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Crystallins are the dominant structural components of the vertebrate eye lens.

Subunit structure

Monomer. Ref.13

Domain

Has a two-domain beta-structure, folded into four very similar Greek key motifs.

Involvement in disease

Cataract 4, multiple types (CTRCT4) [MIM:115700]: 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. CTRCT4 includes crystalline aculeiform, congenital cerulean and non-nuclear polymorphic cataracts, among others. Crystalline aculeiform cataract is characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. Non-nuclear polymorphic cataract is a partial opacity with 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. Congenital cerulean cataract is 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.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19

Sequence similarities

Belongs to the beta/gamma-crystallin family.

Contains 4 beta/gamma crystallin 'Greek key' domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CryaaP246232EBI-7673124,EBI-7673244From a different organism.
CryabP239272EBI-7673124,EBI-299046From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 174173Gamma-crystallin D
PRO_0000057588

Regions

Domain2 – 4039Beta/gamma crystallin 'Greek key' 1
Domain41 – 8343Beta/gamma crystallin 'Greek key' 2
Domain88 – 12841Beta/gamma crystallin 'Greek key' 3
Domain129 – 17143Beta/gamma crystallin 'Greek key' 4
Region84 – 874Connecting peptide

Sites

Site461Susceptible to oxidation

Natural variations

Natural variant151R → C in CTRCT4; progressive punctate cataract with early onset; causes disulfide-linked oligomers formation with consequent protein aggregation and precipitation. Ref.11 Ref.13
VAR_010733
Natural variant241P → S in CTRCT4; lowered solubility. Ref.6 Ref.18
Corresponds to variant rs28931605 [ dbSNP | Ensembl ].
VAR_034955
Natural variant241P → T in CTRCT4; lowered solubility. Ref.6 Ref.15 Ref.16
VAR_021145
Natural variant371R → S in CTRCT4; very low solubility; crystallizes spontaneously. Ref.12 Ref.14
VAR_010734
Natural variant431W → R in CTRCT4; 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 variant591R → H in CTRCT4; lowered solubility; crystallizes easily. Ref.8 Ref.10 Ref.14
VAR_010735
Natural variant1021M → V. Ref.1 Ref.15
VAR_021146
Natural variant1071E → A in CTRCT4. Ref.17
VAR_034956

Experimental info

Mutagenesis24 – 252PN → TK: Wild-type solubility. Ref.6
Mutagenesis241P → TP: Wild-type solubility. Ref.6
Mutagenesis241P → V: Slightly lowered solubility. Ref.6

Secondary structure

...................................... 174
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07320 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 437EC83FD79F12E4

FASTA17420,738
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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 VARIANTS CTRCT4 THR-24 AND SER-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 CTRCT4 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 CTRCT4 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 CTRCT4 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: SUBUNIT, CHARACTERIZATION OF VARIANT CTRCT4 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 CTRCT4 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 CTRCT4 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 CTRCT4 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 CTRCT4 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 CTRCT4 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 CTRCT4 ARG-43, CHARACTERIZATION OF VARIANT CTRCT4 ARG-43.
+Additional computationally mapped references.

Web resources

Eye disease Crystallin, gamma-D (CRYGD)

Leiden Open Variation Database (LOVD)

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.
CCDSCCDS2378.1.
PIRI77413.
RefSeqNP_008822.2. NM_006891.3.
UniGeneHs.546247.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4AX-ray1.15X2-174[»]
1HK0X-ray1.25X2-174[»]
1LD0model-A1-174[»]
2G98X-ray2.20A/B2-174[»]
2KFBNMR-A2-174[»]
2KLJOther-A2-174[»]
4GR7X-ray1.70A/X2-174[»]
4JGFX-ray2.50A/B2-172[»]
ProteinModelPortalP07320.
SMRP07320. Positions 2-174.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107811. 4 interactions.
DIPDIP-46208N.
IntActP07320. 2 interactions.
MINTMINT-8303016.
STRING9606.ENSP00000264376.

PTM databases

PhosphoSiteP07320.

Polymorphism databases

DMDM2506321.

Proteomic databases

MaxQBP07320.
PaxDbP07320.
PeptideAtlasP07320.
PRIDEP07320.

Protocols and materials databases

DNASU1421.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264376; ENSP00000264376; ENSG00000118231.
GeneID1421.
KEGGhsa:1421.
UCSCuc002vcn.4. human.

Organism-specific databases

CTD1421.
GeneCardsGC02M208986.
HGNCHGNC:2411. CRYGD.
MIM115700. phenotype.
123690. gene.
neXtProtNX_P07320.
Orphanet1377. Cataract-microcornea syndrome.
98989. Cerulean cataract.
98986. Coppock-like cataract.
98990. Coralliform cataract.
98991. Nuclear cataract.
98995. Zonular cataract.
PharmGKBPA26918.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG309484.
HOGENOMHOG000234389.
HOVERGENHBG003364.
InParanoidP07320.
OMARGQMMEF.
OrthoDBEOG70CR7Z.
PhylomeDBP07320.

Gene expression databases

BgeeP07320.
CleanExHS_CRYGD.
GenevestigatorP07320.

Family and domain databases

InterProIPR001064. Beta/gamma_crystallin.
IPR011024. G_crystallin-rel.
[Graphical view]
PfamPF00030. Crystall. 2 hits.
[Graphical view]
PRINTSPR01367. BGCRYSTALLIN.
SMARTSM00247. XTALbg. 2 hits.
[Graphical view]
SUPFAMSSF49695. SSF49695. 1 hit.
PROSITEPS50915. CRYSTALLIN_BETA_GAMMA. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP07320.
GeneWikiCrystallin,_gamma_D.
GenomeRNAi1421.
NextBio5811.
PROP07320.
SOURCESearch...

Entry information

Entry nameCRGD_HUMAN
AccessionPrimary (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 9, 2014
This is version 160 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM