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O43186 (CRX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cone-rod homeobox protein
Gene names
Name:CRX
Synonyms:CORD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length299 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors. Ref.6

Subunit structure

Interacts (via the homeobox) with NRL (via the leucine-zipper domain). Interacts with PDC, RAX2, RORB and SCA7. Ref.7 Ref.8

Subcellular location

Nucleus By similarity.

Tissue specificity

Retina.

Involvement in disease

Leber congenital amaurosis 7 (LCA7) [MIM:613829]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.10 Ref.11 Ref.14

Cone-rod dystrophy 2 (CORD2) [MIM:120970]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.9 Ref.10

Retinitis pigmentosa (RP) [MIM:268000]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10

Sequence similarities

Belongs to the paired homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Sensory transduction
Transcription
Transcription regulation
Vision
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseCone-rod dystrophy
Disease mutation
Leber congenital amaurosis
Retinitis pigmentosa
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian rhythm

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Traceable author statement Ref.1. Source: ProtInc

positive regulation of photoreceptor cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

response to stimulus

Inferred from electronic annotation. Source: UniProtKB-KW

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

visual perception

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentnucleus

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

leucine zipper domain binding

Inferred from physical interaction Ref.7. Source: UniProtKB

nuclear hormone receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 299299Cone-rod homeobox protein
PRO_0000048862

Regions

DNA binding39 – 9860Homeobox

Natural variations

Natural variant411R → Q in RP. Ref.9 Ref.10
VAR_007946
Natural variant411R → W in CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL. Ref.7 Ref.9
VAR_003750
Natural variant421E → K Found in a patient with LCA7. Ref.15
VAR_067189
Natural variant801E → A in CORD2. Ref.1 Ref.10
Corresponds to variant rs28939682 [ dbSNP | Ensembl ].
VAR_003751
Natural variant881K → N in LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm. Ref.14
VAR_063919
Natural variant901R → W in LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL. Ref.7 Ref.11
VAR_008714
Natural variant1221G → D in RP.
Corresponds to variant rs61748441 [ dbSNP | Ensembl ].
VAR_008282
Natural variant1411S → F in a breast cancer sample; somatic mutation. Ref.12
VAR_036438
Natural variant146 – 1494Missing in LCA7.
VAR_007947
Natural variant1541T → A. Ref.13
VAR_067190
Natural variant1581A → T. Ref.9
Corresponds to variant rs61748445 [ dbSNP | Ensembl ].
VAR_007948
Natural variant2421V → M in CORD2. Ref.9
VAR_007949

Sequences

Sequence LengthMass (Da)Tools
O43186 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 46747C09277A0864

FASTA29932,261
        10         20         30         40         50         60 
MMAYMNPGPH YSVNALALSG PSVDLMHQAV PYPSAPRKQR RERTTFTRSQ LEELEALFAK 

        70         80         90        100        110        120 
TQYPDVYARE EVALKINLPE SRVQVWFKNR RAKCRQQRQQ QKQQQQPPGG QAKARPAKRK 

       130        140        150        160        170        180 
AGTSPRPSTD VCPDPLGISD SYSPPLPGPS GSPTTAVATV SIWSPASESP LPEAQRAGLV 

       190        200        210        220        230        240 
ASGPSLTSAP YAMTYAPASA FCSSPSAYGS PSSYFSGLDP YLSPMVPQLG GPALSPLSGP 

       250        260        270        280        290 
SVGPSLAQSP TSLSGQSYGA YSPVDSLEFK DPTGTWKFTY NPMDPLDYKD QSAWKFQIL 

« Hide

References

« Hide 'large scale' references
[1]"Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor."
Freund C.L., Gregory-Evans C.Y., Furukawa T., Papaioannou M., Looser J., Ploder L., Bellingham J., Ng D., Herbrick J.-A.S., Duncan A., Scherer S.W., Tsui L.-C., Loutradis-Anagnostou A., Jacobson S.G., Cepko C.L., Bhattacharya S.S., McInnes R.R.
Cell 91:543-553(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CORD2 ALA-80.
[2]"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].
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [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: Eye.
[5]"Mapping of transcription start sites of human retina expressed genes."
Roni V., Carpio R., Wissinger B.
BMC Genomics 8:42-42(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
Tissue: Retina.
[6]"Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression."
Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., Shinohara T.
J. Biol. Chem. 275:1152-1160(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation."
Mitton K.P., Swain P.K., Chen S., Xu S., Zack D.J., Swaroop A.
J. Biol. Chem. 275:29794-29799(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NRL, CHARACTERIZATION OF VARIANT CORD2 TRP-41, CHARACTERIZATION OF VARIANT LCA7 TRP-90.
[8]"QRX, a novel homeobox gene, modulates photoreceptor gene expression."
Wang Q.-L., Chen S., Esumi N., Swain P.K., Haines H.S., Peng G., Melia B.M., McIntosh I., Heckenlively J.R., Jacobson S.G., Stone E.M., Swaroop A., Zack D.J.
Hum. Mol. Genet. 13:1025-1040(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAX2.
[9]"Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration."
Swain P.K., Chen S., Wang Q.-L., Affatigato L.M., Coats C.L., Brady K.D., Fishman G.A., Jacobson S.G., Swaroop A., Stone E., Sieving P.A., Zack D.J.
Neuron 19:1329-1336(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, VARIANT THR-158.
[10]"A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene."
Sohocki M.M., Sullivan L.S., Mintz-Hittner H.A., Birch D., Heckenlively J.R., Freund C.L., McInnes R.R., Daiger S.P.
Am. J. Hum. Genet. 63:1307-1315(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RP GLN-41, VARIANT CORD2 ALA-80, VARIANT LCA7 146-LEU--PRO-149 DEL.
[11]"Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function."
Swaroop A., Wang Q.-L., Wu W., Cook J., Coats C., Xu S., Chen S., Zack D.J., Sieving P.A.
Hum. Mol. Genet. 8:299-305(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LCA7 TRP-90.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-141.
[13]"Molecular characterization of Leber congenital amaurosis in Koreans."
Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.
Mol. Vis. 14:1429-1436(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-154.
[14]"Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL."
Nichols L.L. II, Alur R.P., Boobalan E., Sergeev Y.V., Caruso R.C., Stone E.M., Swaroop A., Johnson M.A., Brooks B.P.
Hum. Mutat. 31:E1472-E1483(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LCA7 ASN-88, CHARACTERIZATION OF VARIANT LCA7 ASN-88.
[15]"Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis."
Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J.F.
PLoS ONE 6:E19458-E19458(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LYS-42.
+Additional computationally mapped references.

Web resources

Mutations of the CRX gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF024711 Genomic DNA. Translation: AAB88418.1.
BT007364 mRNA. Translation: AAP36028.1.
AC008745 Genomic DNA. No translation available.
BC016664 mRNA. No translation available.
BC053672 mRNA. No translation available.
DQ426868 mRNA. Translation: ABD90533.1.
CCDSCCDS12706.1.
RefSeqNP_000545.1. NM_000554.4.
UniGeneHs.617342.
Hs.633434.
Hs.639114.

3D structure databases

ProteinModelPortalO43186.
SMRO43186. Positions 34-95.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107796. 11 interactions.
IntActO43186. 3 interactions.
MINTMINT-1442706.
STRING9606.ENSP00000221996.

PTM databases

PhosphoSiteO43186.

Proteomic databases

PaxDbO43186.
PRIDEO43186.

Protocols and materials databases

DNASU1406.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221996; ENSP00000221996; ENSG00000105392.
ENST00000539067; ENSP00000445565; ENSG00000105392.
GeneID1406.
KEGGhsa:1406.
UCSCuc002phq.4. human.

Organism-specific databases

CTD1406.
GeneCardsGC19P048347.
GeneReviewsCRX.
HGNCHGNC:2383. CRX.
HPAHPA036762.
HPA036763.
MIM120970. phenotype.
268000. phenotype.
602225. gene.
613829. phenotype.
neXtProtNX_O43186.
Orphanet1872. Cone rod dystrophy.
65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
PharmGKBPA26903.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324074.
HOGENOMHOG000082677.
HOVERGENHBG004028.
InParanoidO43186.
KOK09337.
OMAQTKARPA.
PhylomeDBO43186.
TreeFamTF351179.

Gene expression databases

ArrayExpressO43186.
BgeeO43186.
CleanExHS_CRX.
GenevestigatorO43186.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR013851. Otx_TF_C.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03529. TF_Otx. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCRX. human.
GeneWikiCRX_(gene).
GenomeRNAi1406.
NextBio5749.
PROO43186.
SOURCESearch...

Entry information

Entry nameCRX_HUMAN
AccessionPrimary (citable) accession number: O43186
Secondary accession number(s): Q0QD45
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 142 of the entry and version 1 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

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 19

Human chromosome 19: entries, gene names and cross-references to MIM