ID CRX_HUMAN Reviewed; 299 AA. AC O43186; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 25-JAN-2012, entry version 116. DE RecName: Full=Cone-rod homeobox protein; GN Name=CRX; Synonyms=CORD2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CORD2 ALA-80. RX MEDLINE=98050929; PubMed=9390563; DOI=10.1016/S0092-8674(00)80440-7; RA Freund C.L., Gregory-Evans C.Y., Furukawa T., Papaioannou M., RA Looser J., Ploder L., Bellingham J., Ng D., Herbrick J.-A.S., RA Duncan A., Scherer S.W., Tsui L.-C., Loutradis-Anagnostou A., RA Jacobson S.G., Cepko C.L., Bhattacharya S.S., McInnes R.R.; RT "Cone-rod dystrophy due to mutations in a novel photoreceptor-specific RT homeobox gene (CRX) essential for maintenance of the photoreceptor."; RL Cell 91:543-553(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION. RX MEDLINE=20092886; PubMed=10625658; DOI=10.1074/jbc.275.2.1152; RA Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., RA Shinohara T.; RT "Both PCE-1/RX and OTX/CRX interactions are necessary for RT photoreceptor-specific gene expression."; RL J. Biol. Chem. 275:1152-1160(2000). RN [6] RP INTERACTION WITH NRL, CHARACTERIZATION OF VARIANT CORD2 TRP-41, AND RP CHARACTERIZATION OF VARIANT LCA7 TRP-90. RX PubMed=10887186; DOI=10.1074/jbc.M003658200; RA Mitton K.P., Swain P.K., Chen S., Xu S., Zack D.J., Swaroop A.; RT "The leucine zipper of NRL interacts with the CRX homeodomain. A RT possible mechanism of transcriptional synergy in rhodopsin RT regulation."; RL J. Biol. Chem. 275:29794-29799(2000). RN [7] RP INTERACTION WITH RAX2. RX PubMed=15028672; DOI=10.1093/hmg/ddh117; RA Wang Q.-L., Chen S., Esumi N., Swain P.K., Haines H.S., Peng G., RA Melia B.M., McIntosh I., Heckenlively J.R., Jacobson S.G., Stone E.M., RA Swaroop A., Zack D.J.; RT "QRX, a novel homeobox gene, modulates photoreceptor gene RT expression."; RL Hum. Mol. Genet. 13:1025-1040(2004). RN [8] RP VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, AND VARIANT RP THR-158. RX MEDLINE=98087127; PubMed=9427255; DOI=10.1016/S0896-6273(00)80423-7; RA Swain P.K., Chen S., Wang Q.-L., Affatigato L.M., Coats C.L., RA Brady K.D., Fishman G.A., Jacobson S.G., Swaroop A., Stone E., RA Sieving P.A., Zack D.J.; RT "Mutations in the cone-rod homeobox gene are associated with the cone- RT rod dystrophy photoreceptor degeneration."; RL Neuron 19:1329-1336(1997). RN [9] RP VARIANT RP GLN-41, VARIANT CORD2 ALA-80, AND VARIANT LCA7 RP 146-LEU--PRO-149 DEL. RX MEDLINE=99011251; PubMed=9792858; DOI=10.1086/302101; RA Sohocki M.M., Sullivan L.S., Mintz-Hittner H.A., Birch D., RA Heckenlively J.R., Freund C.L., McInnes R.R., Daiger S.P.; RT "A range of clinical phenotypes associated with mutations in CRX, a RT photoreceptor transcription-factor gene."; RL Am. J. Hum. Genet. 63:1307-1315(1998). RN [10] RP VARIANT LCA7 TRP-90. RX MEDLINE=99135909; PubMed=9931337; DOI=10.1093/hmg/8.2.299; RA Swaroop A., Wang Q.-L., Wu W., Cook J., Coats C., Xu S., Chen S., RA Zack D.J., Sieving P.A.; RT "Leber congenital amaurosis caused by a homozygous mutation (R90W) in RT the homeodomain of the retinal transcription factor CRX: direct RT evidence for the involvement of CRX in the development of RT photoreceptor function."; RL Hum. Mol. Genet. 8:299-305(1999). RN [11] RP VARIANT [LARGE SCALE ANALYSIS] PHE-141. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). RN [12] RP VARIANT LCA7 ASN-88, AND CHARACTERIZATION OF VARIANT LCA7 ASN-88. RX PubMed=20513135; DOI=10.1002/humu.21268; RA Nichols L.L. II, Alur R.P., Boobalan E., Sergeev Y.V., Caruso R.C., RA Stone E.M., Swaroop A., Johnson M.A., Brooks B.P.; RT "Two novel CRX mutant proteins causing autosomal dominant Leber RT congenital amaurosis interact differently with NRL."; RL Hum. Mutat. 31:E1472-E1483(2010). CC -!- FUNCTION: Binds and transactivates the sequence 5'-TAATC[CA]-3' CC which is found upstream of several photoreceptor-specific genes, CC including the opsin genes. Acts synergistically with other CC transcription factors, e.g. NRL and RX, to regulate photoreceptor CC cell-specific gene transcription. Essential for the maintenance of CC mammalian photoreceptors. CC -!- SUBUNIT: Interacts with SCA7 (By similarity). Interacts with RAX2. CC Interacts (via the homeobox) with NRL (via the leucine-zipper CC domain). CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). CC -!- TISSUE SPECIFICITY: Retina. CC -!- DISEASE: Defects in CRX are the cause of Leber congenital CC amaurosis type 7 (LCA7) [MIM:613829]. LCA designates a clinically CC and genetically heterogeneous group of childhood retinal CC degenerations, generally inherited in an autosomal recessive CC manner. Affected infants have little or no retinal photoreceptor CC function as tested by electroretinography. LCA represents the most CC common genetic cause of congenital visual impairment in infants CC and children. CC -!- DISEASE: Defects in CRX are the cause of cone-rod dystrophy type 2 CC (CORD2) [MIM:120970]; also known as cone-rod retinal dystrophy 2 CC (CRD2). CORDs are inherited retinal dystrophies belonging to the CC group of pigmentary retinopathies. CORDs are characterized by CC retinal pigment deposits visible on fundus examination, CC predominantly in the macular region, and initial loss of cone CC photoreceptors followed by rod degeneration. This leads to CC decreased visual acuity and sensitivity in the central visual CC field, followed by loss of peripheral vision. Severe loss of CC vision occurs earlier than in retinitis pigmentosa. CC -!- DISEASE: Defects in CRX are a cause of retinitis pigmentosa (RP) CC [MIM:268000]. RP leads to degeneration of retinal photoreceptor CC cells. Patients typically have night vision blindness and loss of CC midperipheral visual field. As their condition progresses, they CC lose their far peripheral visual field and eventually central CC vision as well. CC -!- SIMILARITY: Belongs to the paired homeobox family. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC -!- WEB RESOURCE: Name=Mutations of the CRX gene; Note=Retina CC International's Scientific Newsletter; CC URL="http://www.retina-international.com/sci-news/crxmut.htm"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CRX"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF024711; AAB88418.1; -; Genomic_DNA. DR EMBL; BT007364; AAP36028.1; -; mRNA. DR EMBL; AC008745; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016664; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC053672; -; NOT_ANNOTATED_CDS; mRNA. DR IPI; IPI00011226; -. DR RefSeq; NP_000545.1; NM_000554.4. DR UniGene; Hs.617342; -. DR UniGene; Hs.633434; -. DR UniGene; Hs.639114; -. DR ProteinModelPortal; O43186; -. DR SMR; O43186; 34-95. DR IntAct; O43186; 3. DR MINT; MINT-1442706; -. DR STRING; O43186; -. DR PhosphoSite; O43186; -. DR PRIDE; O43186; -. DR Ensembl; ENST00000221996; ENSP00000221996; ENSG00000105392. DR GeneID; 1406; -. DR KEGG; hsa:1406; -. DR UCSC; uc002phq.2; human. DR CTD; 1406; -. DR GeneCards; GC19P048325; -. DR H-InvDB; HIX0015282; -. DR HGNC; HGNC:2383; CRX. DR HPA; HPA036762; -. DR HPA; HPA036763; -. DR MIM; 120970; phenotype. DR MIM; 268000; phenotype. DR MIM; 602225; gene. DR MIM; 613829; phenotype. DR neXtProt; NX_O43186; -. DR Orphanet; 1872; Cone rod dystrophy. DR Orphanet; 65; Congenital Leber amaurosis. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA26903; -. DR HOGENOM; HBG713848; -. DR HOVERGEN; HBG004028; -. DR InParanoid; O43186; -. DR OMA; QTKARPA; -. DR OrthoDB; EOG4NKBWG; -. DR PhylomeDB; O43186; -. DR NextBio; 5749; -. DR ArrayExpress; O43186; -. DR Bgee; O43186; -. DR CleanEx; HS_CRX; -. DR Genevestigator; O43186; -. DR GermOnline; ENSG00000105392; Homo sapiens. DR GO; GO:0043522; F:leucine zipper domain binding; IPI:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc. DR GO; GO:0009887; P:organ morphogenesis; TAS:ProtInc. DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR InterPro; IPR001356; Homeobox. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR012287; Homeodomain-rel. DR InterPro; IPR013851; Otx_TF_C. DR Gene3D; G3DSA:1.10.10.60; Homeodomain-rel; 1. DR KO; K09337; -. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF03529; TF_Otx; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain_like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. PE 1: Evidence at protein level; KW Activator; Complete proteome; Cone-rod dystrophy; Disease mutation; KW DNA-binding; Homeobox; Leber congenital amaurosis; Nucleus; KW Polymorphism; Reference proteome; Retinitis pigmentosa; KW Sensory transduction; Transcription; Transcription regulation; Vision. FT CHAIN 1 299 Cone-rod homeobox protein. FT /FTId=PRO_0000048862. FT DNA_BIND 39 98 Homeobox. FT VARIANT 41 41 R -> Q (in RP). FT /FTId=VAR_007946. FT VARIANT 41 41 R -> W (in CORD2; exhibits reduced DNA FT binding, transcriptional synergy and FT interaction with NRL). FT /FTId=VAR_003750. FT VARIANT 80 80 E -> A (in CORD2; dbSNP:rs28939682). FT /FTId=VAR_003751. FT VARIANT 88 88 K -> N (in LCA7; reduces NRL FT transactivation and reduces steady state FT levels of CRX and NRL; altered FT localization to the cytoplasm). FT /FTId=VAR_063919. FT VARIANT 90 90 R -> W (in LCA7; reduced DNA-binding FT ability, transcriptional synergy and FT interaction with NRL). FT /FTId=VAR_008714. FT VARIANT 122 122 G -> D (in RP). FT /FTId=VAR_008282. FT VARIANT 141 141 S -> F (in a breast cancer sample; FT somatic mutation). FT /FTId=VAR_036438. FT VARIANT 146 149 Missing (in LCA7). FT /FTId=VAR_007947. FT VARIANT 158 158 A -> T. FT /FTId=VAR_007948. FT VARIANT 242 242 V -> M (in CORD2). FT /FTId=VAR_007949. SQ SEQUENCE 299 AA; 32261 MW; 46747C09277A0864 CRC64; MMAYMNPGPH YSVNALALSG PSVDLMHQAV PYPSAPRKQR RERTTFTRSQ LEELEALFAK TQYPDVYARE EVALKINLPE SRVQVWFKNR RAKCRQQRQQ QKQQQQPPGG QAKARPAKRK AGTSPRPSTD VCPDPLGISD SYSPPLPGPS GSPTTAVATV SIWSPASESP LPEAQRAGLV ASGPSLTSAP YAMTYAPASA FCSSPSAYGS PSSYFSGLDP YLSPMVPQLG GPALSPLSGP SVGPSLAQSP TSLSGQSYGA YSPVDSLEFK DPTGTWKFTY NPMDPLDYKD QSAWKFQIL //