CRX_HUMAN
ID CRX_HUMAN Reviewed; 299 AA.
AC O43186; Q0QD45;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Cone-rod homeobox protein;
GN Name=CRX; Synonyms=CORD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CORD2 ALA-80.
RX PubMed=9390563; DOI=10.1016/s0092-8674(00)80440-7;
RA Freund C.L., Gregory-Evans C.Y., Furukawa T., Papaioannou M., Looser J.,
RA Ploder L., Bellingham J., Ng D., Herbrick J.-A.S., Duncan A., Scherer S.W.,
RA Tsui L.-C., Loutradis-Anagnostou A., Jacobson S.G., Cepko C.L.,
RA 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 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
RC TISSUE=Retina;
RX PubMed=17286855; DOI=10.1186/1471-2164-8-42;
RA Roni V., Carpio R., Wissinger B.;
RT "Mapping of transcription start sites of human retina expressed genes.";
RL BMC Genomics 8:42-42(2007).
RN [6]
RP FUNCTION.
RX PubMed=10625658; DOI=10.1074/jbc.275.2.1152;
RA Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., Shinohara T.;
RT "Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-
RT specific gene expression.";
RL J. Biol. Chem. 275:1152-1160(2000).
RN [7]
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 possible
RT mechanism of transcriptional synergy in rhodopsin regulation.";
RL J. Biol. Chem. 275:29794-29799(2000).
RN [8]
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 expression.";
RL Hum. Mol. Genet. 13:1025-1040(2004).
RN [9]
RP VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, AND VARIANT THR-158.
RX 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., Brady K.D.,
RA Fishman G.A., Jacobson S.G., Swaroop A., Stone E., Sieving P.A., Zack D.J.;
RT "Mutations in the cone-rod homeobox gene are associated with the cone-rod
RT dystrophy photoreceptor degeneration.";
RL Neuron 19:1329-1336(1997).
RN [10]
RP VARIANT RP GLN-41, VARIANT CORD2 ALA-80, AND VARIANT LCA7 146-LEU--PRO-149
RP DEL.
RX 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 [11]
RP VARIANT LCA7 TRP-90.
RX 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 the
RT homeodomain of the retinal transcription factor CRX: direct evidence for
RT the involvement of CRX in the development of photoreceptor function.";
RL Hum. Mol. Genet. 8:299-305(1999).
RN [12]
RP VARIANTS ASP-10; ILE-66; ASP-122 AND THR-158, AND VARIANTS RP GLN-41 AND
RP GLN-115.
RX PubMed=11139241; DOI=10.1002/1098-1004(2001)17:1<42::aid-humu5>3.0.co;2-k;
RA Sohocki M.M., Daiger S.P., Bowne S.J., Rodriquez J.A., Northrup H.,
RA Heckenlively J.R., Birch D.G., Mintz-Hittner H., Ruiz R.S., Lewis R.A.,
RA Saperstein D.A., Sullivan L.S.;
RT "Prevalence of mutations causing retinitis pigmentosa and other inherited
RT retinopathies.";
RL Hum. Mutat. 17:42-51(2001).
RN [13]
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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [14]
RP VARIANT ALA-154.
RX PubMed=18682808;
RA Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.;
RT "Molecular characterization of Leber congenital amaurosis in Koreans.";
RL Mol. Vis. 14:1429-1436(2008).
RN [15]
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 congenital
RT amaurosis interact differently with NRL.";
RL Hum. Mutat. 31:E1472-E1483(2010).
RN [16]
RP VARIANT LCA7 LYS-42.
RX PubMed=21602930; DOI=10.1371/journal.pone.0019458;
RA Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q.,
RA Hejtmancik J.F.;
RT "Detection of variants in 15 genes in 87 unrelated Chinese patients with
RT Leber congenital amaurosis.";
RL PLoS ONE 6:E19458-E19458(2011).
RN [17]
RP VARIANT ASP-122.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Transcription factor that binds and transactivates the
CC sequence 5'-TAATC[CA]-3' which is found upstream of several
CC photoreceptor-specific genes, including the opsin genes. Acts
CC synergistically with other transcription factors, such as NRL, RORB and
CC RAX, to regulate photoreceptor cell-specific gene transcription.
CC Essential for the maintenance of mammalian photoreceptors.
CC {ECO:0000269|PubMed:10625658}.
CC -!- SUBUNIT: Interacts (via the homeobox) with NRL (via the leucine-zipper
CC domain). Interacts with PDC, RAX2, RORB and SCA7.
CC {ECO:0000269|PubMed:10887186, ECO:0000269|PubMed:15028672}.
CC -!- INTERACTION:
CC O43186; Q9NRN7: AASDHPPT; NbExp=3; IntAct=EBI-748171, EBI-740884;
CC O43186; Q9NYB9: ABI2; NbExp=5; IntAct=EBI-748171, EBI-743598;
CC O43186; K7EM05: ACBD4; NbExp=3; IntAct=EBI-748171, EBI-16431307;
CC O43186; O95376: ARIH2; NbExp=3; IntAct=EBI-748171, EBI-711158;
CC O43186; O94817: ATG12; NbExp=3; IntAct=EBI-748171, EBI-746742;
CC O43186; Q8N8Y2: ATP6V0D2; NbExp=3; IntAct=EBI-748171, EBI-3923949;
CC O43186; P54253: ATXN1; NbExp=3; IntAct=EBI-748171, EBI-930964;
CC O43186; Q9H503-2: BANF2; NbExp=3; IntAct=EBI-748171, EBI-11977289;
CC O43186; A0A0S2Z5G4: BANP; NbExp=3; IntAct=EBI-748171, EBI-16429704;
CC O43186; B4DE54: BANP; NbExp=3; IntAct=EBI-748171, EBI-16429313;
CC O43186; Q8N9N5-2: BANP; NbExp=6; IntAct=EBI-748171, EBI-11524452;
CC O43186; Q8N9N5-7: BANP; NbExp=3; IntAct=EBI-748171, EBI-16429296;
CC O43186; Q8IYS8: BOD1L2; NbExp=3; IntAct=EBI-748171, EBI-12118438;
CC O43186; Q9UFG5: C19orf25; NbExp=3; IntAct=EBI-748171, EBI-741214;
CC O43186; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-748171, EBI-8643161;
CC O43186; Q9BV19: C1orf50; NbExp=3; IntAct=EBI-748171, EBI-2874661;
CC O43186; Q96LT7: C9orf72; NbExp=3; IntAct=EBI-748171, EBI-2961725;
CC O43186; P35219: CA8; NbExp=7; IntAct=EBI-748171, EBI-718700;
CC O43186; P24863: CCNC; NbExp=4; IntAct=EBI-748171, EBI-395261;
CC O43186; P42773: CDKN2C; NbExp=3; IntAct=EBI-748171, EBI-711290;
CC O43186; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-748171, EBI-749051;
CC O43186; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-748171, EBI-11962928;
CC O43186; Q14154: DELE1; NbExp=3; IntAct=EBI-748171, EBI-2805660;
CC O43186; P63241: EIF5A; NbExp=3; IntAct=EBI-748171, EBI-373150;
CC O43186; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-748171, EBI-12013806;
CC O43186; O75593: FOXH1; NbExp=3; IntAct=EBI-748171, EBI-1759806;
CC O43186; O75603: GCM2; NbExp=11; IntAct=EBI-748171, EBI-10188645;
CC O43186; Q9BZE0: GLIS2; NbExp=3; IntAct=EBI-748171, EBI-7251368;
CC O43186; Q96NT3: GUCD1; NbExp=3; IntAct=EBI-748171, EBI-8293751;
CC O43186; P13807: GYS1; NbExp=3; IntAct=EBI-748171, EBI-740553;
CC O43186; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-748171, EBI-14103818;
CC O43186; O14964: HGS; NbExp=6; IntAct=EBI-748171, EBI-740220;
CC O43186; P35680: HNF1B; NbExp=3; IntAct=EBI-748171, EBI-2798841;
CC O43186; Q86VF2-5: IGFN1; NbExp=3; IntAct=EBI-748171, EBI-11955401;
CC O43186; P78412: IRX6; NbExp=3; IntAct=EBI-748171, EBI-12100506;
CC O43186; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-748171, EBI-2556193;
CC O43186; Q5THT1: KLHL32; NbExp=3; IntAct=EBI-748171, EBI-10247181;
CC O43186; Q71RC2-6: LARP4; NbExp=3; IntAct=EBI-748171, EBI-10255841;
CC O43186; P17931: LGALS3; NbExp=3; IntAct=EBI-748171, EBI-1170392;
CC O43186; P0CW20: LIMS4; NbExp=3; IntAct=EBI-748171, EBI-10196832;
CC O43186; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-748171, EBI-739832;
CC O43186; Q17RB8: LONRF1; NbExp=5; IntAct=EBI-748171, EBI-2341787;
CC O43186; Q8TC57: M1AP; NbExp=4; IntAct=EBI-748171, EBI-748182;
CC O43186; Q9BUN1: MENT; NbExp=3; IntAct=EBI-748171, EBI-12022316;
CC O43186; Q6P2C6: MLLT6; NbExp=3; IntAct=EBI-748171, EBI-5773143;
CC O43186; Q9NP98: MYOZ1; NbExp=3; IntAct=EBI-748171, EBI-744402;
CC O43186; Q969S2: NEIL2; NbExp=3; IntAct=EBI-748171, EBI-10281234;
CC O43186; Q13952-2: NFYC; NbExp=3; IntAct=EBI-748171, EBI-11956831;
CC O43186; Q9Y221: NIP7; NbExp=3; IntAct=EBI-748171, EBI-749003;
CC O43186; P34130: NTF4; NbExp=3; IntAct=EBI-748171, EBI-3907456;
CC O43186; O95007: OR6B1; NbExp=3; IntAct=EBI-748171, EBI-12176191;
CC O43186; Q9UJX0: OSGIN1; NbExp=3; IntAct=EBI-748171, EBI-9057006;
CC O43186; Q7Z2X4: PID1; NbExp=3; IntAct=EBI-748171, EBI-10256685;
CC O43186; P0CW24: PNMA6A; NbExp=3; IntAct=EBI-748171, EBI-721270;
CC O43186; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-748171, EBI-1389308;
CC O43186; Q96T49: PPP1R16B; NbExp=4; IntAct=EBI-748171, EBI-10293968;
CC O43186; O43741: PRKAB2; NbExp=9; IntAct=EBI-748171, EBI-1053424;
CC O43186; P0CG20: PRR35; NbExp=3; IntAct=EBI-748171, EBI-11986293;
CC O43186; P25786: PSMA1; NbExp=3; IntAct=EBI-748171, EBI-359352;
CC O43186; P40306: PSMB10; NbExp=3; IntAct=EBI-748171, EBI-603329;
CC O43186; Q2TAL8: QRICH1; NbExp=6; IntAct=EBI-748171, EBI-2798044;
CC O43186; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-748171, EBI-372094;
CC O43186; A1L4F5: ROR2; NbExp=3; IntAct=EBI-748171, EBI-10172778;
CC O43186; Q01974: ROR2; NbExp=4; IntAct=EBI-748171, EBI-6422642;
CC O43186; Q9UBE0: SAE1; NbExp=3; IntAct=EBI-748171, EBI-743154;
CC O43186; O00560: SDCBP; NbExp=3; IntAct=EBI-748171, EBI-727004;
CC O43186; Q9UDX3: SEC14L4; NbExp=3; IntAct=EBI-748171, EBI-10320311;
CC O43186; P84022: SMAD3; NbExp=3; IntAct=EBI-748171, EBI-347161;
CC O43186; Q8IYB5-2: SMAP1; NbExp=3; IntAct=EBI-748171, EBI-12061577;
CC O43186; Q8WU79: SMAP2; NbExp=3; IntAct=EBI-748171, EBI-2822515;
CC O43186; Q53HV7: SMUG1; NbExp=3; IntAct=EBI-748171, EBI-749970;
CC O43186; P56693: SOX10; NbExp=3; IntAct=EBI-748171, EBI-1167533;
CC O43186; O95416: SOX14; NbExp=3; IntAct=EBI-748171, EBI-9087806;
CC O43186; P41225: SOX3; NbExp=3; IntAct=EBI-748171, EBI-9078386;
CC O43186; P35711: SOX5; NbExp=4; IntAct=EBI-748171, EBI-3505701;
CC O43186; P35711-4: SOX5; NbExp=3; IntAct=EBI-748171, EBI-11954419;
CC O43186; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-748171, EBI-742688;
CC O43186; O75716: STK16; NbExp=3; IntAct=EBI-748171, EBI-749295;
CC O43186; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-748171, EBI-740595;
CC O43186; P51687: SUOX; NbExp=3; IntAct=EBI-748171, EBI-3921347;
CC O43186; Q5T011-5: SZT2; NbExp=3; IntAct=EBI-748171, EBI-10245139;
CC O43186; O95947: TBX6; NbExp=3; IntAct=EBI-748171, EBI-2824328;
CC O43186; Q9NQB0-10: TCF7L2; NbExp=3; IntAct=EBI-748171, EBI-11746252;
CC O43186; O43247-2: TEX33; NbExp=3; IntAct=EBI-748171, EBI-12093053;
CC O43186; Q92734: TFG; NbExp=3; IntAct=EBI-748171, EBI-357061;
CC O43186; Q08117: TLE5; NbExp=3; IntAct=EBI-748171, EBI-717810;
CC O43186; Q08117-2: TLE5; NbExp=3; IntAct=EBI-748171, EBI-11741437;
CC O43186; O43711: TLX3; NbExp=3; IntAct=EBI-748171, EBI-3939165;
CC O43186; Q63HR2: TNS2; NbExp=3; IntAct=EBI-748171, EBI-949753;
CC O43186; Q14CS0: UBXN2B; NbExp=3; IntAct=EBI-748171, EBI-1993619;
CC O43186; O94888: UBXN7; NbExp=3; IntAct=EBI-748171, EBI-1993627;
CC O43186; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-748171, EBI-2559305;
CC O43186; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-748171, EBI-742550;
CC O43186; Q15915: ZIC1; NbExp=3; IntAct=EBI-748171, EBI-11963196;
CC O43186; Q6P088: ZNF483; NbExp=3; IntAct=EBI-748171, EBI-10196963;
CC O43186; A0A0S2Z6P0: ZNF688; NbExp=3; IntAct=EBI-748171, EBI-16429989;
CC O43186; P03410: tax; Xeno; NbExp=3; IntAct=EBI-748171, EBI-9676218;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- TISSUE SPECIFICITY: Retina.
CC -!- DISEASE: Leber congenital amaurosis 7 (LCA7) [MIM:613829]: A severe
CC dystrophy of the retina, typically becoming evident in the first years
CC of life. Visual function is usually poor and often accompanied by
CC nystagmus, sluggish or near-absent pupillary responses, photophobia,
CC high hyperopia and keratoconus. {ECO:0000269|PubMed:10887186,
CC ECO:0000269|PubMed:20513135, ECO:0000269|PubMed:21602930,
CC ECO:0000269|PubMed:9792858, ECO:0000269|PubMed:9931337}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cone-rod dystrophy 2 (CORD2) [MIM:120970]: An inherited
CC retinal dystrophy characterized by retinal pigment deposits visible on
CC fundus examination, predominantly in the macular region, and initial
CC loss of cone photoreceptors followed by rod degeneration. This leads to
CC decreased visual acuity and sensitivity in the central visual field,
CC followed by loss of peripheral vision. Severe loss of vision occurs
CC earlier than in retinitis pigmentosa, due to cone photoreceptors
CC degenerating at a higher rate than rod photoreceptors.
CC {ECO:0000269|PubMed:10887186, ECO:0000269|PubMed:9390563,
CC ECO:0000269|PubMed:9427255, ECO:0000269|PubMed:9792858}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Retinitis pigmentosa (RP) [MIM:268000]: A retinal dystrophy
CC belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:11139241,
CC ECO:0000269|PubMed:9427255, ECO:0000269|PubMed:9792858}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the CRX gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/crxmut.htm";
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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 EMBL; DQ426868; ABD90533.1; -; mRNA.
DR CCDS; CCDS12706.1; -.
DR RefSeq; NP_000545.1; NM_000554.5.
DR AlphaFoldDB; O43186; -.
DR SASBDB; O43186; -.
DR SMR; O43186; -.
DR BioGRID; 107796; 117.
DR IntAct; O43186; 109.
DR MINT; O43186; -.
DR STRING; 9606.ENSP00000221996; -.
DR iPTMnet; O43186; -.
DR PhosphoSitePlus; O43186; -.
DR BioMuta; CRX; -.
DR MassIVE; O43186; -.
DR PaxDb; O43186; -.
DR PeptideAtlas; O43186; -.
DR PRIDE; O43186; -.
DR ProteomicsDB; 48803; -.
DR Antibodypedia; 31635; 270 antibodies from 33 providers.
DR DNASU; 1406; -.
DR Ensembl; ENST00000221996.12; ENSP00000221996.5; ENSG00000105392.16.
DR Ensembl; ENST00000539067.5; ENSP00000445565.1; ENSG00000105392.16.
DR GeneID; 1406; -.
DR KEGG; hsa:1406; -.
DR MANE-Select; ENST00000221996.12; ENSP00000221996.5; NM_000554.6; NP_000545.1.
DR UCSC; uc002phq.5; human.
DR CTD; 1406; -.
DR DisGeNET; 1406; -.
DR GeneCards; CRX; -.
DR GeneReviews; CRX; -.
DR HGNC; HGNC:2383; CRX.
DR HPA; ENSG00000105392; Tissue enriched (retina).
DR MalaCards; CRX; -.
DR MIM; 120970; phenotype.
DR MIM; 268000; phenotype.
DR MIM; 602225; gene.
DR MIM; 613829; phenotype.
DR neXtProt; NX_O43186; -.
DR OpenTargets; ENSG00000105392; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR Orphanet; 65; Leber congenital amaurosis.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA26903; -.
DR VEuPathDB; HostDB:ENSG00000105392; -.
DR eggNOG; KOG2251; Eukaryota.
DR GeneTree; ENSGT00940000161634; -.
DR HOGENOM; CLU_064370_0_0_1; -.
DR InParanoid; O43186; -.
DR OMA; TWKFAYN; -.
DR OrthoDB; 1481439at2759; -.
DR PhylomeDB; O43186; -.
DR TreeFam; TF351179; -.
DR PathwayCommons; O43186; -.
DR SignaLink; O43186; -.
DR SIGNOR; O43186; -.
DR BioGRID-ORCS; 1406; 18 hits in 1094 CRISPR screens.
DR ChiTaRS; CRX; human.
DR GeneWiki; CRX_(gene); -.
DR GenomeRNAi; 1406; -.
DR Pharos; O43186; Tbio.
DR PRO; PR:O43186; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O43186; protein.
DR Bgee; ENSG00000105392; Expressed in pigmented layer of retina and 36 other tissues.
DR ExpressionAtlas; O43186; baseline and differential.
DR Genevisible; O43186; HS.
DR GO; GO:0000785; C:chromatin; ISS:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISS:ARUK-UCL.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISS:ARUK-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0043522; F:leucine zipper domain binding; IPI:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:ARUK-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:ARUK-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR013851; Otx_TF_C.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03529; TF_Otx; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Cone-rod dystrophy; Developmental protein; Differentiation;
KW Disease variant; DNA-binding; Homeobox; Leber congenital amaurosis;
KW Neurogenesis; Nucleus; Reference proteome; Retinitis pigmentosa;
KW Sensory transduction; Transcription; Transcription regulation; Vision.
FT CHAIN 1..299
FT /note="Cone-rod homeobox protein"
FT /id="PRO_0000048862"
FT DNA_BIND 39..98
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 93..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 10
FT /note="H -> D (in dbSNP:rs139340178)"
FT /evidence="ECO:0000269|PubMed:11139241"
FT /id="VAR_076956"
FT VARIANT 41
FT /note="R -> Q (in RP; dbSNP:rs61748436)"
FT /evidence="ECO:0000269|PubMed:11139241,
FT ECO:0000269|PubMed:9427255, ECO:0000269|PubMed:9792858"
FT /id="VAR_007946"
FT VARIANT 41
FT /note="R -> W (in CORD2; exhibits reduced DNA binding,
FT transcriptional synergy and interaction with NRL;
FT dbSNP:rs104894672)"
FT /evidence="ECO:0000269|PubMed:10887186,
FT ECO:0000269|PubMed:9427255"
FT /id="VAR_003750"
FT VARIANT 42
FT /note="E -> K (in LCA7; unknown pathological significance;
FT dbSNP:rs863224863)"
FT /evidence="ECO:0000269|PubMed:21602930"
FT /id="VAR_067189"
FT VARIANT 66
FT /note="V -> I (in dbSNP:rs61748438)"
FT /evidence="ECO:0000269|PubMed:11139241"
FT /id="VAR_076957"
FT VARIANT 80
FT /note="E -> A (in CORD2; dbSNP:rs104894671)"
FT /evidence="ECO:0000269|PubMed:9390563,
FT ECO:0000269|PubMed:9792858"
FT /id="VAR_003751"
FT VARIANT 88
FT /note="K -> N (in LCA7; reduces NRL transactivation and
FT reduces steady state levels of CRX and NRL; altered
FT localization to the cytoplasm)"
FT /evidence="ECO:0000269|PubMed:20513135"
FT /id="VAR_063919"
FT VARIANT 90
FT /note="R -> W (in LCA7; reduced DNA-binding ability,
FT transcriptional synergy and interaction with NRL;
FT dbSNP:rs104894673)"
FT /evidence="ECO:0000269|PubMed:10887186,
FT ECO:0000269|PubMed:9931337"
FT /id="VAR_008714"
FT VARIANT 115
FT /note="R -> Q (in RP; unknown pathological significance;
FT dbSNP:rs750727986)"
FT /evidence="ECO:0000269|PubMed:11139241"
FT /id="VAR_076958"
FT VARIANT 122
FT /note="G -> D (in dbSNP:rs61748441)"
FT /evidence="ECO:0000269|PubMed:11139241,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_008282"
FT VARIANT 141
FT /note="S -> F (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1165723137)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036438"
FT VARIANT 146..149
FT /note="Missing (in LCA7)"
FT /evidence="ECO:0000269|PubMed:9792858"
FT /id="VAR_007947"
FT VARIANT 154
FT /note="T -> A (in dbSNP:rs763651232)"
FT /evidence="ECO:0000269|PubMed:18682808"
FT /id="VAR_067190"
FT VARIANT 158
FT /note="A -> T (in dbSNP:rs61748445)"
FT /evidence="ECO:0000269|PubMed:11139241,
FT ECO:0000269|PubMed:9427255"
FT /id="VAR_007948"
FT VARIANT 242
FT /note="V -> M (in CORD2; dbSNP:rs61748459)"
FT /evidence="ECO:0000269|PubMed:9427255"
FT /id="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
