Reviewed, UniProtKB/Swiss-Prot O43186 (CRX_HUMAN)

Names and origin

Protein names

Recommended name:
    Cone-rod homeobox protein

Gene names

Name:	CRX
Synonyms:	CORD2

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	299 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Essential for the maintenance of mammalian photoreceptors.
Subunit structure	Interacts with SCA7 By similarity. Interacts with RAX2.
Subcellular location	Nucleus By similarity.
Tissue specificity	Retina.
Involvement in disease	Defects in CRX are the cause of Leber congenital amaurosis type 7 (LCA7) [MIM:602225]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children. Ref.6 Ref.7 Defects in CRX are the cause of cone-rod dystrophy type 2 (CORD2) [MIM:120970]; also known as cone-rod retinal dystrophy 2 (CRD2). CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are 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. Ref.6 Ref.1 Ref.5 Defects in CRX are a cause of retinitis pigmentosa (RP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. 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. Ref.6 Ref.5
Sequence similarities	Belongs to the paired homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Sensory transduction Transcription Transcription regulation Vision
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Cone-rod dystrophy Disease mutation Leber congenital amaurosis Retinitis pigmentosa
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	organ morphogenesis Ref.1 Traceable author statement. Source: ProtInc response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW visual perception Ref.1 Traceable author statement. Source: ProtInc
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.1 Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 299	299	Cone-rod homeobox protein		PRO_0000048862
Regions
	DNA binding	39 – 98	60	Homeobox
Natural variations
	Natural variant	41	1	R → Q in RP. Ref.6 Ref.5		VAR_007946
	Natural variant	41	1	R → W in CORD2. Ref.5		VAR_003750
	Natural variant	80	1	E → A in CORD2. Ref.6 Ref.1		VAR_003751
	Natural variant	90	1	R → W in LCA7; reduced DNA-binding ability. Ref.7		VAR_008714
	Natural variant	122	1	G → D in RP.		VAR_008282
	Natural variant	141	1	S → F in a breast cancer sample; somatic mutation. Ref.8		VAR_036438
	Natural variant	146 – 149	4	Missing in LCA7.		VAR_007947
	Natural variant	158	1	A → T		VAR_007948
	Natural variant	242	1	V → M in CORD2. Ref.5		VAR_007949

Sequences

	Sequence		Length	Mass (Da)
	O43186-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 46747C09277A0864	FASTA	299	32,261
	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

References

	« Hide 'large scale' referencesShow '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: 9390563] [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 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: Eye.
[4]	"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: 15028672] [Abstract] Cited for: INTERACTION WITH RAX2.
[5]	"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: 9427255] [Abstract] Cited for: VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, VARIANT THR-158.
[6]	"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: 9792858] [Abstract] Cited for: VARIANT RP GLN-41, VARIANT CORD2 ALA-80, VARIANT LCA7 146-LEU--PRO-149 DEL.
[7]	"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: 9931337] [Abstract] Cited for: VARIANT LCA7 TRP-90.
[8]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-141.
+	Additional computationally mapped references.

Web resources

Mutations of the CRX gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF024711 Genomic DNA. Translation: AAB88418.1. BT007364 mRNA. Translation: AAP36028.1. BC016664 mRNA. Translation: AAH16664.1. BC053672 mRNA. Translation: AAH53672.1.
IPI	IPI00011226.
RefSeq	NP_000545.1.
UniGene	Hs.617342 Hs.633434 Hs.639114
3D structure databases
HSSP	HSSP built from PDB template 1FJL based on UniProtKB P06601.
SMR	O43186. Positions 34-95.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43186. 2 interactions.
STRING	O43186.
Proteomic databases
PRIDE	O43186.
Genome annotation databases
Ensembl	ENST00000221996; ENSP00000221996; ENSG00000105392; Homo sapiens. [Genome view]
GeneID	1406.
KEGG	hsa:1406.
UCSC	uc002phq.2. human.
Organism-specific databases
CTD	1406.
GeneCards	GC19P053016.
H-InvDB	HIX0015282.
HGNC	HGNC:2383. CRX.
MIM	120970. phenotype. 268000. phenotype. 602225. gene+phenotype.
Orphanet	1872. Cone rod dystrophy. 65. Leber amaurosis, congenital. 791. Retinitis pigmentosa.
PharmGKB	PA26903.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O43186.
HOVERGEN	O43186.
OMA	LSGQSYS.
Gene expression databases
ArrayExpress	O43186.
Bgee	O43186.
CleanEx	HS_CRX.
Genevestigator	O43186.
GermOnline	ENSG00000105392. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	5749.
SOURCE	Search...

Entry information

Entry name

CRX_HUMAN

Accession

Primary (citable) accession number: O43186

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 1, 1998
Last modified:	November 3, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.