OTX2_HUMAN
ID OTX2_HUMAN Reviewed; 289 AA.
AC P32243; B2RAN5; Q6GTV3; Q9HAW3; Q9P2R1;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Homeobox protein OTX2;
DE AltName: Full=Orthodenticle homolog 2;
GN Name=OTX2;
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 [MRNA] (ISOFORM 2).
RX PubMed=8101484; DOI=10.1002/j.1460-2075.1993.tb05935.x;
RA Simeone A., Acampora D., Mallamaci A., Stornaiuolo A., D'Apice M.R.,
RA Nigro V., Boncinelli E.;
RT "A vertebrate gene related to orthodenticle contains a homeodomain of the
RT bicoid class and demarcates anterior neuroectoderm in the gastrulating
RT mouse embryo.";
RL EMBO J. 12:2735-2747(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Perrault I., Rozet J.-M., Gerber S., Munnich A., Kaplan J.;
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=10372988; DOI=10.1076/ceyr.18.4.283.5360;
RA Fong S.L., Fong W.B.;
RT "Elements regulating the transcription of human interstitial retinoid-
RT binding protein (IRBP) gene in cultured retinoblastoma cells.";
RL Curr. Eye Res. 18:283-291(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 171-283.
RA Kitano T., Kobayakawa H., Saitou N.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP VARIANTS MCOPS5 GLY-89; THR-133 AND ALA-134, AND DEVELOPMENTAL STAGE.
RX PubMed=15846561; DOI=10.1086/430721;
RA Ragge N.K., Brown A.G., Poloschek C.M., Lorenz B., Henderson R.A.,
RA Clarke M.P., Russell-Eggitt I., Fielder A., Gerrelli D.,
RA Martinez-Barbera J.P., Ruddle P., Hurst J., Collin J.R., Salt A.,
RA Cooper S.T., Thompson P.J., Sisodiya S.M., Williamson K.A.,
RA Fitzpatrick D.R., van Heyningen V., Hanson I.M.;
RT "Heterozygous mutations of OTX2 cause severe ocular malformations.";
RL Am. J. Hum. Genet. 76:1008-1022(2005).
RN [9]
RP ERRATUM OF PUBMED:15846561.
RA Ragge N.K., Brown A.G., Poloschek C.M., Lorenz B., Henderson R.A.,
RA Clarke M.P., Russell-Eggitt I., Fielder A., Gerrelli D.,
RA Martinez-Barbera J.P., Ruddle P., Hurst J., Collin J.R., Salt A.,
RA Cooper S.T., Thompson P.J., Sisodiya S.M., Williamson K.A.,
RA Fitzpatrick D.R., van Heyningen V., Hanson I.M.;
RL Am. J. Hum. Genet. 77:334-334(2005).
RN [10]
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=19414065; DOI=10.1016/j.ijdevneu.2009.04.004;
RA Larsen K.B., Lutterodt M., Rath M.F., Moeller M.;
RT "Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human
RT fetal retina.";
RL Int. J. Dev. Neurosci. 27:485-492(2009).
RN [11]
RP INVOLVEMENT IN RDEOP.
RX PubMed=19956411;
RA Henderson R.H., Williamson K.A., Kennedy J.S., Webster A.R., Holder G.E.,
RA Robson A.G., FitzPatrick D.R., van Heyningen V., Moore A.T.;
RT "A rare de novo nonsense mutation in OTX2 causes early onset retinal
RT dystrophy and pituitary dysfunction.";
RL Mol. Vis. 15:2442-2447(2009).
RN [12]
RP INVOLVEMENT IN MCOPS5.
RX PubMed=22577225; DOI=10.1136/jmedgenet-2012-100892;
RA Chassaing N., Sorrentino S., Davis E.E., Martin-Coignard D., Iacovelli A.,
RA Paznekas W., Webb B.D., Faye-Petersen O., Encha-Razavi F., Lequeux L.,
RA Vigouroux A., Yesilyurt A., Boyadjiev S.A., Kayserili H., Loget P.,
RA Carles D., Sergi C., Puvabanditsin S., Chen C.P., Etchevers H.C.,
RA Katsanis N., Mercer C.L., Calvas P., Jabs E.W.;
RT "OTX2 mutations contribute to the otocephaly-dysgnathia complex.";
RL J. Med. Genet. 49:373-379(2012).
RN [13]
RP INVOLVEMENT IN MCOPS5.
RX PubMed=24167467; DOI=10.1159/000353727;
RA Patat O., van Ravenswaaij-Arts C.M., Tantau J., Corsten-Janssen N.,
RA van Tintelen J.P., Dijkhuizen T., Kaplan J., Chassaing N.;
RT "Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation
RT of the Role of OTX2.";
RL Mol. Syndromol. 4:302-305(2013).
RN [14]
RP INVOLVEMENT IN RDEOP, AND VARIANT RDEOP LYS-79.
RX PubMed=25293953; DOI=10.1136/jmedgenet-2014-102620;
RG FORGE Canada Consortium;
RA Vincent A., Forster N., Maynes J.T., Paton T.A., Billingsley G.,
RA Roslin N.M., Ali A., Sutherland J., Wright T., Westall C.A., Paterson A.D.,
RA Marshall C.R., Heon E.;
RT "OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal
RT pigment epithelium.";
RL J. Med. Genet. 51:797-805(2014).
RN [15]
RP VARIANT CPHD6 SER-225, AND CHARACTERIZATION OF VARIANT CPHD6 SER-225.
RX PubMed=18728160; DOI=10.1210/jc.2008-1189;
RA Diaczok D., Romero C., Zunich J., Marshall I., Radovick S.;
RT "A novel dominant negative mutation of OTX2 associated with combined
RT pituitary hormone deficiency.";
RL J. Clin. Endocrinol. Metab. 93:4351-4359(2008).
RN [16]
RP VARIANT MCOPS5 SER-90, AND CHARACTERIZATION OF VARIANT MCOPS5 SER-90.
RX PubMed=20396904; DOI=10.1007/s00439-010-0820-9;
RA Ashkenazi-Hoffnung L., Lebenthal Y., Wyatt A.W., Ragge N.K., Dateki S.,
RA Fukami M., Ogata T., Phillip M., Gat-Yablonski G.;
RT "A novel loss-of-function mutation in OTX2 in a patient with anophthalmia
RT and isolated growth hormone deficiency.";
RL Hum. Genet. 127:721-729(2010).
RN [17]
RP VARIANT CPHD6 ARG-134, AND FUNCTION.
RX PubMed=22715480; DOI=10.1530/eje-12-0333;
RA Gorbenko Del Blanco D., Romero C.J., Diaczok D., de Graaff L.C.,
RA Radovick S., Hokken-Koelega A.C.;
RT "A novel OTX2 mutation in a patient with combined pituitary hormone
RT deficiency, pituitary malformation, and an underdeveloped left optic
RT nerve.";
RL Eur. J. Endocrinol. 167:441-452(2012).
CC -!- FUNCTION: Transcription factor probably involved in the development of
CC the brain and the sense organs. Can bind to the bicoid/BCD target
CC sequence (BTS): 5'-TCTAATCCC-3'. {ECO:0000269|PubMed:22715480}.
CC -!- INTERACTION:
CC P32243-2; Q96FT7: ASIC4; NbExp=3; IntAct=EBI-9087860, EBI-9116154;
CC P32243-2; Q96LB4-4: ATP6V1G3; NbExp=3; IntAct=EBI-9087860, EBI-12941272;
CC P32243-2; P54253: ATXN1; NbExp=3; IntAct=EBI-9087860, EBI-930964;
CC P32243-2; Q9UQB9: AURKC; NbExp=4; IntAct=EBI-9087860, EBI-3926851;
CC P32243-2; Q8NHY0: B4GALNT2; NbExp=3; IntAct=EBI-9087860, EBI-1042940;
CC P32243-2; Q12982: BNIP2; NbExp=3; IntAct=EBI-9087860, EBI-752094;
CC P32243-2; Q00526: CDK3; NbExp=3; IntAct=EBI-9087860, EBI-1245761;
CC P32243-2; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-9087860, EBI-356015;
CC P32243-2; Q9Y5Y3: GPR45; NbExp=3; IntAct=EBI-9087860, EBI-1751869;
CC P32243-2; Q9UMX6: GUCA1B; NbExp=3; IntAct=EBI-9087860, EBI-12896859;
CC P32243-2; Q53FT3: HIKESHI; NbExp=3; IntAct=EBI-9087860, EBI-6137602;
CC P32243-2; P35680: HNF1B; NbExp=3; IntAct=EBI-9087860, EBI-2798841;
CC P32243-2; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-9087860, EBI-748420;
CC P32243-2; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-9087860, EBI-3918847;
CC P32243-2; P46940: IQGAP1; NbExp=3; IntAct=EBI-9087860, EBI-297509;
CC P32243-2; Q9UK76: JPT1; NbExp=3; IntAct=EBI-9087860, EBI-720411;
CC P32243-2; P57682: KLF3; NbExp=3; IntAct=EBI-9087860, EBI-8472267;
CC P32243-2; Q8TC57: M1AP; NbExp=3; IntAct=EBI-9087860, EBI-748182;
CC P32243-2; Q9GZZ1: NAA50; NbExp=3; IntAct=EBI-9087860, EBI-1052523;
CC P32243-2; Q8NH93: OR1L3; NbExp=3; IntAct=EBI-9087860, EBI-13080292;
CC P32243-2; Q96RD1: OR6C1; NbExp=3; IntAct=EBI-9087860, EBI-12905112;
CC P32243-2; Q13153: PAK1; NbExp=3; IntAct=EBI-9087860, EBI-1307;
CC P32243-2; Q8WUT1: POLDIP3; NbExp=3; IntAct=EBI-9087860, EBI-10276663;
CC P32243-2; A0AV96: RBM47; NbExp=3; IntAct=EBI-9087860, EBI-2823850;
CC P32243-2; Q8TAA1: RNASE11; NbExp=3; IntAct=EBI-9087860, EBI-13063024;
CC P32243-2; P62854: RPS26; NbExp=3; IntAct=EBI-9087860, EBI-353438;
CC P32243-2; O00442-2: RTCA; NbExp=3; IntAct=EBI-9087860, EBI-12886464;
CC P32243-2; P09012: SNRPA; NbExp=3; IntAct=EBI-9087860, EBI-607085;
CC P32243-2; Q5QJ74: TBCEL; NbExp=3; IntAct=EBI-9087860, EBI-10244795;
CC P32243-2; Q96A09: TENT5B; NbExp=3; IntAct=EBI-9087860, EBI-752030;
CC P32243-2; P17152: TMEM11; NbExp=3; IntAct=EBI-9087860, EBI-723946;
CC P32243-2; O14787-2: TNPO2; NbExp=3; IntAct=EBI-9087860, EBI-12076664;
CC P32243-2; Q6PF06: TRMT10B; NbExp=3; IntAct=EBI-9087860, EBI-3923391;
CC P32243-2; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-9087860, EBI-742550;
CC P32243-2; Q7L2R6-2: ZNF765; NbExp=3; IntAct=EBI-9087860, EBI-12834294;
CC P32243-2; O43257: ZNHIT1; NbExp=3; IntAct=EBI-9087860, EBI-347522;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19414065}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32243-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32243-2; Sequence=VSP_021006;
CC -!- DEVELOPMENTAL STAGE: At Carnegie stage (CS) 14, widely expressed
CC throughout the telencephalon and mesencephalon, with a sharp cutoff at
CC the midbrain-hindbrain boundary. At CS16, found in the lamina
CC terminalis and the floor of the telencephalon. At CS16-CS19, in the
CC developing eye, strongly expressed in the retinal pigment epithelium
CC layer and more weakly in the neural retina, not expressed in the optic
CC nerve itself (at protein level). Retinal expression peaks between CS19
CC and CS21 and decline in older fetuses. At CS22, detected in the choroid
CC plexus, the dorsal thalamus, and the roof of the mesencephalon. In the
CC developing nasal structures, expressed in the olfactory epithelium of
CC the nasal pits at CS18. {ECO:0000269|PubMed:15846561,
CC ECO:0000269|PubMed:19414065}.
CC -!- DISEASE: Microphthalmia, syndromic, 5 (MCOPS5) [MIM:610125]: Patients
CC manifest unilateral or bilateral microphthalmia/clinical anophthalmia
CC and variable additional features including pituitary dysfunction,
CC coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or
CC agenesis of the optic nerve, agenesis of the corpus callosum,
CC developmental delay, joint laxity, hypotonia, and seizures.
CC Microphthalmia is a disorder of eye formation, ranging from small size
CC of a single eye to complete bilateral absence of ocular tissues
CC (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in
CC association with syndromes that include non-ocular abnormalities.
CC {ECO:0000269|PubMed:15846561, ECO:0000269|PubMed:20396904,
CC ECO:0000269|PubMed:22577225, ECO:0000269|PubMed:24167467}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pituitary hormone deficiency, combined, 6 (CPHD6)
CC [MIM:613986]: Combined pituitary hormone deficiency is defined as the
CC impaired production of growth hormone and one or more of the other five
CC anterior pituitary hormones. CPHD6 patients manifest neonatal
CC hypoglycemia, and deficiencies of growth hormone, thyroid-stimulating
CC hormone, luteinizing hormone, follicle stimulating hormone and
CC adrenocorticotropic hormone. {ECO:0000269|PubMed:18728160,
CC ECO:0000269|PubMed:22715480}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Retinal dystrophy, early-onset, with or without pituitary
CC dysfunction (RDEOP) [MIM:610125]: An autosomal dominant ocular disease
CC characterized by pattern dystrophy of the retinal pigment epithelium,
CC and photoreceptor degeneration. Mild developmental anomalies include
CC optic nerve head dysplasia, microcornea, and Rathke's cleft cyst. Some
CC patients manifest pituitary dysfunction. {ECO:0000269|PubMed:19956411,
CC ECO:0000269|PubMed:25293953}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/OTX2ID46429ch14q22.html";
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DR EMBL; AF298117; AAG16243.1; -; Genomic_DNA.
DR EMBL; AF093138; AAD31385.1; -; mRNA.
DR EMBL; AK314271; BAG36932.1; -; mRNA.
DR EMBL; CH471061; EAW80692.1; -; Genomic_DNA.
DR EMBL; BC032579; AAH32579.1; -; mRNA.
DR EMBL; AB037505; BAA90425.1; -; Genomic_DNA.
DR CCDS; CCDS41960.1; -. [P32243-1]
DR CCDS; CCDS9728.1; -. [P32243-2]
DR RefSeq; NP_001257452.1; NM_001270523.1. [P32243-1]
DR RefSeq; NP_001257453.1; NM_001270524.1. [P32243-1]
DR RefSeq; NP_001257454.1; NM_001270525.1. [P32243-2]
DR RefSeq; NP_068374.1; NM_021728.3. [P32243-2]
DR RefSeq; NP_758840.1; NM_172337.2. [P32243-1]
DR AlphaFoldDB; P32243; -.
DR BMRB; P32243; -.
DR SMR; P32243; -.
DR BioGRID; 111055; 66.
DR IntAct; P32243; 40.
DR MINT; P32243; -.
DR STRING; 9606.ENSP00000343819; -.
DR MoonDB; P32243; Predicted.
DR GlyGen; P32243; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P32243; -.
DR PhosphoSitePlus; P32243; -.
DR BioMuta; OTX2; -.
DR EPD; P32243; -.
DR jPOST; P32243; -.
DR MassIVE; P32243; -.
DR PaxDb; P32243; -.
DR PeptideAtlas; P32243; -.
DR PRIDE; P32243; -.
DR ProteomicsDB; 54851; -. [P32243-1]
DR ProteomicsDB; 54852; -. [P32243-2]
DR Antibodypedia; 49; 438 antibodies from 38 providers.
DR DNASU; 5015; -.
DR Ensembl; ENST00000339475.10; ENSP00000343819.5; ENSG00000165588.19. [P32243-1]
DR Ensembl; ENST00000408990.8; ENSP00000386185.3; ENSG00000165588.19. [P32243-1]
DR Ensembl; ENST00000554845.2; ENSP00000451357.2; ENSG00000165588.19. [P32243-2]
DR Ensembl; ENST00000555006.5; ENSP00000452336.1; ENSG00000165588.19. [P32243-1]
DR Ensembl; ENST00000555804.2; ENSP00000451272.2; ENSG00000165588.19. [P32243-1]
DR Ensembl; ENST00000672264.2; ENSP00000500115.1; ENSG00000165588.19. [P32243-2]
DR Ensembl; ENST00000673035.1; ENSP00000500061.1; ENSG00000165588.19. [P32243-1]
DR Ensembl; ENST00000673481.1; ENSP00000500595.1; ENSG00000165588.19. [P32243-2]
DR Ensembl; ENST00000685244.1; ENSP00000508798.1; ENSG00000165588.19. [P32243-1]
DR GeneID; 5015; -.
DR KEGG; hsa:5015; -.
DR MANE-Select; ENST00000672264.2; ENSP00000500115.1; NM_021728.4; NP_068374.1. [P32243-2]
DR UCSC; uc001xcp.5; human. [P32243-1]
DR CTD; 5015; -.
DR DisGeNET; 5015; -.
DR GeneCards; OTX2; -.
DR HGNC; HGNC:8522; OTX2.
DR HPA; ENSG00000165588; Group enriched (choroid plexus, retina).
DR MalaCards; OTX2; -.
DR MIM; 600037; gene.
DR MIM; 610125; phenotype.
DR MIM; 613986; phenotype.
DR neXtProt; NX_P32243; -.
DR OpenTargets; ENSG00000165588; -.
DR Orphanet; 990; Agnathia-holoprosencephaly-situs inversus syndrome.
DR Orphanet; 99001; Butterfly-shaped pigment dystrophy.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 95494; Combined pituitary hormone deficiencies, genetic forms.
DR Orphanet; 35612; Nanophthalmos.
DR Orphanet; 3157; Septo-optic dysplasia spectrum.
DR Orphanet; 178364; Syndromic microphthalmia type 5.
DR PharmGKB; PA32849; -.
DR VEuPathDB; HostDB:ENSG00000165588; -.
DR eggNOG; KOG2251; Eukaryota.
DR GeneTree; ENSGT00940000155014; -.
DR HOGENOM; CLU_064370_0_0_1; -.
DR InParanoid; P32243; -.
DR OMA; KSPHYAM; -.
DR OrthoDB; 935804at2759; -.
DR PhylomeDB; P32243; -.
DR TreeFam; TF351179; -.
DR PathwayCommons; P32243; -.
DR SignaLink; P32243; -.
DR SIGNOR; P32243; -.
DR BioGRID-ORCS; 5015; 21 hits in 1092 CRISPR screens.
DR GeneWiki; Orthodenticle_homeobox_2; -.
DR GenomeRNAi; 5015; -.
DR Pharos; P32243; Tbio.
DR PRO; PR:P32243; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P32243; protein.
DR Bgee; ENSG00000165588; Expressed in secondary oocyte and 47 other tissues.
DR ExpressionAtlas; P32243; baseline and differential.
DR Genevisible; P32243; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; TAS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0007411; P:axon guidance; IDA:UniProtKB.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0030900; P:forebrain development; TAS:UniProtKB.
DR GO; GO:0030901; P:midbrain development; TAS:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; ISS:UniProtKB.
DR GO; GO:2000543; P:positive regulation of gastrulation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0090009; P:primitive streak formation; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; TAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR003022; Otx2_TF.
DR InterPro; IPR003025; Otx_TF.
DR InterPro; IPR013851; Otx_TF_C.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03529; TF_Otx; 1.
DR PRINTS; PR01257; OTX2HOMEOBOX.
DR PRINTS; PR01255; OTXHOMEOBOX.
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 Alternative splicing; Developmental protein; Disease variant; DNA-binding;
KW Homeobox; Microphthalmia; Nucleus; Reference proteome.
FT CHAIN 1..289
FT /note="Homeobox protein OTX2"
FT /id="PRO_0000049210"
FT DNA_BIND 38..97
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 93..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..109
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 32
FT /note="P -> PGPWASCPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8101484"
FT /id="VSP_021006"
FT VARIANT 79
FT /note="E -> K (in RDEOP; dbSNP:rs786205224)"
FT /evidence="ECO:0000269|PubMed:25293953"
FT /id="VAR_073793"
FT VARIANT 89
FT /note="R -> G (in MCOPS5; dbSNP:rs104894464)"
FT /evidence="ECO:0000269|PubMed:15846561"
FT /id="VAR_029354"
FT VARIANT 90
FT /note="R -> S (in MCOPS5; does not affect the expression or
FT nuclear localization of the protein but inhibits its DNA-
FT binding activity as well as its transactivation capability;
FT the protein is non-functional)"
FT /evidence="ECO:0000269|PubMed:20396904"
FT /id="VAR_065952"
FT VARIANT 133
FT /note="P -> T (in MCOPS5; dbSNP:rs376333965)"
FT /evidence="ECO:0000269|PubMed:15846561"
FT /id="VAR_029355"
FT VARIANT 134
FT /note="P -> A (in MCOPS5; dbSNP:rs753783256)"
FT /evidence="ECO:0000269|PubMed:15846561"
FT /id="VAR_029356"
FT VARIANT 134
FT /note="P -> R (in CPHD6; unknown pathological significance;
FT loss of transcriptional activity, when tested on bicoid
FT binding sites; decreases transactivation mediated by the
FT wild-type protein, when tested on bicoid binding sites; no
FT effect on DNA-binding; dbSNP:rs199761861)"
FT /evidence="ECO:0000269|PubMed:22715480"
FT /id="VAR_078446"
FT VARIANT 225
FT /note="N -> S (in CPHD6; acts as a dominant inhibitor of
FT the HESX1 gene; dbSNP:rs370761964)"
FT /evidence="ECO:0000269|PubMed:18728160"
FT /id="VAR_065953"
SQ SEQUENCE 289 AA; 31636 MW; 66B86D5EAD6E2E7A CRC64;
MMSYLKQPPY AVNGLSLTTS GMDLLHPSVG YPATPRKQRR ERTTFTRAQL DVLEALFAKT
RYPDIFMREE VALKINLPES RVQVWFKNRR AKCRQQQQQQ QNGGQNKVRP AKKKTSPARE
VSSESGTSGQ FTPPSSTSVP TIASSSAPVS IWSPASISPL SDPLSTSSSC MQRSYPMTYT
QASGYSQGYA GSTSYFGGMD CGSYLTPMHH QLPGPGATLS PMGTNAVTSH LNQSPASLST
QGYGASSLGF NSTTDCLDYK DQTASWKLNF NADCLDYKDQ TSSWKFQVL
