ID PITX2_HUMAN Reviewed; 317 AA. AC Q99697; A8K6C6; B2RA02; B3KXS0; O60578; O60579; O60580; Q3KQX9; Q9BY17; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 27-MAR-2024, entry version 229. DE RecName: Full=Pituitary homeobox 2 {ECO:0000305}; DE AltName: Full=ALL1-responsive protein ARP1; DE AltName: Full=Homeobox protein PITX2; DE AltName: Full=Paired-like homeodomain transcription factor 2; DE AltName: Full=RIEG bicoid-related homeobox transcription factor; DE AltName: Full=Solurshin {ECO:0000303|PubMed:8944018}; GN Name=PITX2 {ECO:0000312|HGNC:HGNC:9005}; GN Synonyms=ARP1, RGS, RIEG, RIEG1 {ECO:0000303|PubMed:8944018}; 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 PTX2B), AND VARIANTS RIEG1 GLN-100; RP PRO-114; PRO-137 AND 179-TRP--VAL-317 DEL. RC TISSUE=Craniofacial, and Fetal brain; RX PubMed=8944018; DOI=10.1038/ng1296-392; RA Semina E.V., Reiter R., Leysens N.J., Alward W.L.M., Small K.W., RA Datson N.A., Siegle-Bartelt J., Bierke-Nelson D., Bitoun P., Zabel B.U., RA Carey J.C., Murray J.C.; RT "Cloning and characterization of a novel bicoid-related homeobox RT transcription factor gene, RIEG, involved in Rieger syndrome."; RL Nat. Genet. 14:392-399(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A; PTX2B AND PTX2C), AND RP ALTERNATIVE SPLICING. RX PubMed=9539779; DOI=10.1073/pnas.95.8.4573; RA Arakawa H., Nakamura T., Zhadanov A.B., Fidanza Y., Yano T., Bullrich F., RA Shimizu M., Blechman J., Mazo A., Canaani E., Croce C.M.; RT "Identification and characterization of the ARP1 gene, a target for the RT human acute leukemia ALL1 gene."; RL Proc. Natl. Acad. Sci. U.S.A. 95:4573-4578(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PTX2A). RA Semina E.V., Funkhauser C., Bitoun P., Daack-Hirsch S., Alward W.L.M., RA Amendt B., Murray J.C.; RT "Spectrum and frequency of PITX2 mutations in patients with Rieger syndrome RT and related ocular anomalies."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS PTX2A; PTX2B AND PTX2C). RC TISSUE=Placenta, and Tongue; 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] (ISOFORMS PTX2C AND PTX2A). RC TISSUE=Lung, and Uterus; 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 INTERACTION WITH EFEMP2. RX PubMed=22919265; RA Acharya M., Sharp M.W., Mirzayans F., Footz T., Huang L., Birdi C., RA Walter M.A.; RT "Yeast two-hybrid analysis of a human trabecular meshwork cDNA library RT identified EFEMP2 as a novel PITX2 interacting protein."; RL Mol. Vis. 18:2182-2189(2012). RN [8] RP STRUCTURE BY NMR OF 85-144 OF WILD-TYPE AND MUTANT HIS-108 IN COMPLEX WITH RP DNA, AND VARIANT RDC HIS-108. RX PubMed=22224469; DOI=10.1021/bi201639x; RA Doerdelmann T., Kojetin D.J., Baird-Titus J.M., Solt L.A., Burris T.P., RA Rance M.; RT "Structural and biophysical insights into the ligand-free Pitx2 homeodomain RT and a ring dermoid of the cornea inducing homeodomain mutant."; RL Biochemistry 51:665-676(2012). RN [9] RP VARIANT ASGD4 TRP-130. RX PubMed=9437321; DOI=10.1016/s0002-9394(99)80242-6; RA Alward W.L.M., Semina E.V., Kalenak J.W., Heon E., Sheth B.P., Stone E.M., RA Murray J.C.; RT "Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger RT syndrome (RIEG/PITX2) gene."; RL Am. J. Ophthalmol. 125:98-100(1998). RN [10] RP VARIANT ASGD4 HIS-115. RX PubMed=9618168; DOI=10.1093/hmg/7.7.1113; RA Kulak S.C., Kozlowski K., Semina E.V., Pearce W.G., Walter M.A.; RT "Mutation in the RIEG1 gene in patients with iridogoniodysgenesis RT syndrome."; RL Hum. Mol. Genet. 7:1113-1117(1998). RN [11] RP INVOLVEMENT IN ASGD4. RX PubMed=10051017; RA Doward W., Perveen R., Lloyd I.C., Ridgway A.E.A., Wilson L., Black G.C.M.; RT "A mutation in the RIEG1 gene associated with Peters' anomaly."; RL J. Med. Genet. 36:152-155(1999). RN [12] RP VARIANTS RIEG1 GLU-134 AND CYS-136. RX PubMed=10937553; RA Perveen R., Lloyd I.C., Clayton-Smith J., Churchill A., van Heyningen V., RA Hanson I., Taylor D., McKeown C., Super M., Kerr B., Winter R., RA Black G.C.M.; RT "Phenotypic variability and asymmetry of Rieger syndrome associated with RT PITX2 mutations."; RL Invest. Ophthalmol. Vis. Sci. 41:2456-2460(2000). RN [13] RP VARIANTS RIEG1 128-ARG--LYS-134 DEL AND LEU-129, AND CHARACTERIZATION OF RP VARIANTS RIEG1 128-ARG--LYS-134 DEL AND LEU-129. RX PubMed=11487566; DOI=10.1093/hmg/10.16.1631; RA Priston M., Kozlowski K., Gill D., Letwin K., Buys Y., Levin A.V., RA Walter M.A., Heon E.; RT "Functional analyses of two newly identified PITX2 mutants reveal a novel RT molecular mechanism for Axenfeld-Rieger syndrome."; RL Hum. Mol. Genet. 10:1631-1638(2001). RN [14] RP VARIANTS RIEG1 LEU-110; CYS-136; VAL-151 AND THR-154. RX PubMed=12381896; DOI=10.1159/000065602; RA Phillips J.C.; RT "Four novel mutations in the PITX2 gene in patients with Axenfeld-Rieger RT syndrome."; RL Ophthalmic Res. 34:324-326(2002). RN [15] RP VARIANT RDC HIS-108. RX PubMed=15591271; DOI=10.1136/jmg.2004.022434; RA Xia K., Wu L., Liu X., Xi X., Liang D., Zheng D., Cai F., Pan Q., Long Z., RA Dai H., Hu Z., Tang B., Zhang Z., Xia J.; RT "Mutation in PITX2 is associated with ring dermoid of the cornea."; RL J. Med. Genet. 41:E129-E129(2004). RN [16] RP VARIANTS RIEG1 LEU-110 AND ARG-110. RX PubMed=16936096; DOI=10.1167/iovs.06-0343; RA Weisschuh N., Dressler P., Schuettauf F., Wolf C., Wissinger B., Gramer E.; RT "Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger RT malformations."; RL Invest. Ophthalmol. Vis. Sci. 47:3846-3852(2006). RN [17] RP ERRATUM OF PUBMED:16936096. RA Weisschuh N., Dressler P., Schuettauf F., Wolf C., Wissinger B., Gramer E.; RL Invest. Ophthalmol. Vis. Sci. 47:5162-5162(2006). RN [18] RP VARIANT ASGD4 LEU-58 (ISOFORM PTX2A). RX PubMed=20881294; DOI=10.1167/iovs.10-5309; RA D'haene B., Meire F., Claerhout I., Kroes H.Y., Plomp A., Arens Y.H., RA de Ravel T., Casteels I., De Jaegere S., Hooghe S., Wuyts W., RA van den Ende J., Roulez F., Veenstra-Knol H.E., Oldenburg R.A., Giltay J., RA Verheij J.B., de Faber J.T., Menten B., De Paepe A., Kestelyn P., RA Leroy B.P., De Baere E.; RT "Expanding the spectrum of FOXC1 and PITX2 mutations and copy number RT changes in patients with anterior segment malformations."; RL Invest. Ophthalmol. Vis. Sci. 52:324-333(2011). CC -!- FUNCTION: May play a role in myoblast differentiation. When CC unphosphorylated, associates with an ELAVL1-containing complex, which CC stabilizes cyclin mRNA and ensuring cell proliferation. Phosphorylation CC by AKT2 impairs this association, leading to CCND1 mRNA destabilization CC and progression towards differentiation. CC {ECO:0000250|UniProtKB:P97474}. CC -!- FUNCTION: [Isoform PTX2C]: Involved in the establishment of left-right CC asymmetry in the developing embryo. {ECO:0000250|UniProtKB:P97474}. CC -!- SUBUNIT: Interacts with EFEMP2 (PubMed:22919265). Interacts (when CC unphosphorylated on Thr-90) with ELAVL1/HUR (By similarity). CC {ECO:0000250|UniProtKB:P97474, ECO:0000269|PubMed:22919265}. CC -!- INTERACTION: CC Q99697; P67809: YBX1; NbExp=3; IntAct=EBI-1175211, EBI-354065; CC Q99697; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-1175211, EBI-3957603; CC Q99697-2; Q9NXR5-2: ANKRD10; NbExp=3; IntAct=EBI-12138495, EBI-12102070; CC Q99697-2; Q86V38: ATN1; NbExp=3; IntAct=EBI-12138495, EBI-11954292; CC Q99697-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12138495, EBI-3867333; CC Q99697-2; Q15038: DAZAP2; NbExp=3; IntAct=EBI-12138495, EBI-724310; CC Q99697-2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-12138495, EBI-742054; CC Q99697-2; P63172: DYNLT1; NbExp=3; IntAct=EBI-12138495, EBI-1176455; CC Q99697-2; Q9Y5J3: HEY1; NbExp=3; IntAct=EBI-12138495, EBI-7231130; CC Q99697-2; P49639: HOXA1; NbExp=3; IntAct=EBI-12138495, EBI-740785; CC Q99697-2; O76011: KRT34; NbExp=3; IntAct=EBI-12138495, EBI-1047093; CC Q99697-2; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-12138495, EBI-11992140; CC Q99697-2; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-12138495, EBI-1048945; CC Q99697-2; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-12138495, EBI-10241353; CC Q99697-2; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-12138495, EBI-3957694; CC Q99697-2; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-12138495, EBI-12111050; CC Q99697-2; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-12138495, EBI-18394498; CC Q99697-2; O43482: OIP5; NbExp=3; IntAct=EBI-12138495, EBI-536879; CC Q99697-2; Q99471: PFDN5; NbExp=3; IntAct=EBI-12138495, EBI-357275; CC Q99697-2; Q16633: POU2AF1; NbExp=3; IntAct=EBI-12138495, EBI-943588; CC Q99697-2; P28070: PSMB4; NbExp=3; IntAct=EBI-12138495, EBI-603350; CC Q99697-2; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-12138495, EBI-740343; CC Q99697-2; Q53HV7-2: SMUG1; NbExp=3; IntAct=EBI-12138495, EBI-12275818; CC Q99697-2; Q96LM6: SPMIP9; NbExp=3; IntAct=EBI-12138495, EBI-743976; CC Q99697-2; Q9Y458: TBX22; NbExp=3; IntAct=EBI-12138495, EBI-6427217; CC Q99697-2; Q9GZM7: TINAGL1; NbExp=3; IntAct=EBI-12138495, EBI-715869; CC Q99697-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12138495, EBI-11741437; CC Q99697-2; Q13077: TRAF1; NbExp=3; IntAct=EBI-12138495, EBI-359224; CC Q99697-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-12138495, EBI-492476; CC Q99697-2; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-12138495, EBI-12068150; CC Q99697-2; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-12138495, EBI-11957216; CC Q99697-2; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-12138495, EBI-12040603; CC Q99697-3; Q12948: FOXC1; NbExp=6; IntAct=EBI-1175243, EBI-1175253; CC Q99697-3; Q02078: MEF2A; NbExp=2; IntAct=EBI-1175243, EBI-2656305; CC Q99697-3; Q99697-3: PITX2; NbExp=5; IntAct=EBI-1175243, EBI-1175243; CC Q99697-3; P10037: Pou1f1; Xeno; NbExp=2; IntAct=EBI-1175243, EBI-9825525; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm CC {ECO:0000250|UniProtKB:P97474}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=PTX2B; Synonyms=ARP1B; CC IsoId=Q99697-1; Sequence=Displayed; CC Name=PTX2C; Synonyms=ARP1C; CC IsoId=Q99697-2; Sequence=VSP_002260; CC Name=PTX2A; Synonyms=ARP1A; CC IsoId=Q99697-3; Sequence=VSP_002261; CC -!- PTM: Phosphorylated at Thr-90 by AKT2, but not AKT1. Phosphorylation CC impairs its association with a CCND1 mRNA-stabilizing complex, thus CC shortening the half-life of CCND1. {ECO:0000250|UniProtKB:P97474}. CC -!- DISEASE: Axenfeld-Rieger syndrome 1 (RIEG1) [MIM:180500]: An autosomal CC dominant disorder of morphogenesis that results in abnormal development CC of the anterior segment of the eye, and results in blindness from CC glaucoma in approximately 50% of affected individuals. Additional CC features include aniridia, maxillary hypoplasia, hypodontia, anal CC stenosis, redundant periumbilical skin. {ECO:0000269|PubMed:10937553, CC ECO:0000269|PubMed:11487566, ECO:0000269|PubMed:12381896, CC ECO:0000269|PubMed:16936096, ECO:0000269|PubMed:8944018}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Anterior segment dysgenesis 4 (ASGD4) [MIM:137600]: A form of CC anterior segment dysgenesis, a group of defects affecting anterior CC structures of the eye including cornea, iris, lens, trabecular CC meshwork, and Schlemm canal. Anterior segment dysgeneses result from CC abnormal migration or differentiation of the neural crest derived CC mesenchymal cells that give rise to components of the anterior chamber CC during eye development. Different anterior segment anomalies may exist CC alone or in combination, including iris hypoplasia, enlarged or reduced CC corneal diameter, corneal vascularization and opacity, posterior CC embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, CC ectopia lentis, and anterior synechiae between the iris and posterior CC corneal surface. Clinical conditions falling within the phenotypic CC spectrum of anterior segment dysgeneses include aniridia, Axenfeld CC anomaly, Reiger anomaly/syndrome, Peters anomaly, and CC iridogoniodysgenesis. ASGD4 is an autosomal dominant disease. CC {ECO:0000269|PubMed:10051017, ECO:0000269|PubMed:20881294, CC ECO:0000269|PubMed:9437321, ECO:0000269|PubMed:9618168}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Ring dermoid of cornea (RDC) [MIM:180550]: An ocular disorder CC characterized by bilateral annular limbal dermoids (growths with a CC skin-like structure) with corneal and conjunctival extension. CC {ECO:0000269|PubMed:15591271, ECO:0000269|PubMed:22224469}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U69961; AAC16257.1; -; mRNA. DR EMBL; AF048720; AAC39716.1; -; mRNA. DR EMBL; AF048721; AAC39717.1; -; mRNA. DR EMBL; AF048722; AAC39718.1; -; mRNA. DR EMBL; AF238048; AAK15048.1; -; Genomic_DNA. DR EMBL; AK127829; BAG54582.1; -; mRNA. DR EMBL; AK291591; BAF84280.1; -; mRNA. DR EMBL; AK313987; BAG36699.1; -; mRNA. DR EMBL; CH471057; EAX06262.1; -; Genomic_DNA. DR EMBL; CH471057; EAX06263.1; -; Genomic_DNA. DR EMBL; CH471057; EAX06264.1; -; Genomic_DNA. DR EMBL; BC013998; AAH13998.1; -; mRNA. DR EMBL; BC106010; AAI06011.1; -; mRNA. DR CCDS; CCDS3692.1; -. [Q99697-1] DR CCDS; CCDS3693.1; -. [Q99697-3] DR CCDS; CCDS3694.1; -. [Q99697-2] DR RefSeq; NP_000316.2; NM_000325.5. [Q99697-2] DR RefSeq; NP_001191326.1; NM_001204397.1. [Q99697-1] DR RefSeq; NP_001191327.1; NM_001204398.1. [Q99697-1] DR RefSeq; NP_001191328.1; NM_001204399.1. [Q99697-3] DR RefSeq; NP_700475.1; NM_153426.2. [Q99697-1] DR RefSeq; NP_700476.1; NM_153427.2. [Q99697-3] DR RefSeq; XP_011530329.1; XM_011532027.2. DR PDB; 2L7F; NMR; -; P=85-144. DR PDB; 2L7M; NMR; -; P=85-144. DR PDB; 2LKX; NMR; -; A=85-144. DR PDBsum; 2L7F; -. DR PDBsum; 2L7M; -. DR PDBsum; 2LKX; -. DR AlphaFoldDB; Q99697; -. DR SMR; Q99697; -. DR BioGRID; 111325; 85. DR CORUM; Q99697; -. DR IntAct; Q99697; 60. DR MINT; Q99697; -. DR STRING; 9606.ENSP00000495061; -. DR iPTMnet; Q99697; -. DR PhosphoSitePlus; Q99697; -. DR BioMuta; PITX2; -. DR DMDM; 6174907; -. DR EPD; Q99697; -. DR jPOST; Q99697; -. DR MassIVE; Q99697; -. DR MaxQB; Q99697; -. DR PaxDb; 9606-ENSP00000304169; -. DR PeptideAtlas; Q99697; -. DR ProteomicsDB; 78403; -. [Q99697-1] DR ProteomicsDB; 78404; -. [Q99697-2] DR ProteomicsDB; 78405; -. [Q99697-3] DR Pumba; Q99697; -. DR Antibodypedia; 15459; 333 antibodies from 31 providers. DR DNASU; 5308; -. DR Ensembl; ENST00000354925.6; ENSP00000347004.2; ENSG00000164093.18. [Q99697-1] DR Ensembl; ENST00000355080.9; ENSP00000347192.5; ENSG00000164093.18. [Q99697-3] DR Ensembl; ENST00000394595.8; ENSP00000378095.4; ENSG00000164093.18. [Q99697-1] DR Ensembl; ENST00000644743.1; ENSP00000495061.1; ENSG00000164093.18. [Q99697-2] DR GeneID; 5308; -. DR KEGG; hsa:5308; -. DR MANE-Select; ENST00000644743.1; ENSP00000495061.1; NM_000325.6; NP_000316.2. [Q99697-2] DR UCSC; uc003iac.4; human. [Q99697-1] DR AGR; HGNC:9005; -. DR DisGeNET; 5308; -. DR GeneCards; PITX2; -. DR HGNC; HGNC:9005; PITX2. DR HPA; ENSG00000164093; Tissue enhanced (placenta, skeletal muscle, tongue, urinary bladder). DR MalaCards; PITX2; -. DR MIM; 137600; phenotype. DR MIM; 180500; phenotype. DR MIM; 180550; phenotype. DR MIM; 601542; gene. DR neXtProt; NX_Q99697; -. DR OpenTargets; ENSG00000164093; -. DR Orphanet; 98978; Axenfeld anomaly. DR Orphanet; 782; Axenfeld-Rieger syndrome. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 708; Peters anomaly. DR Orphanet; 91483; Rieger anomaly. DR Orphanet; 91481; Ring dermoid of cornea. DR PharmGKB; PA33339; -. DR VEuPathDB; HostDB:ENSG00000164093; -. DR eggNOG; KOG0486; Eukaryota. DR GeneTree; ENSGT00940000162789; -. DR HOGENOM; CLU_030301_0_0_1; -. DR InParanoid; Q99697; -. DR OMA; MNCLKEP; -. DR OrthoDB; 5395268at2759; -. DR PhylomeDB; Q99697; -. DR TreeFam; TF351940; -. DR PathwayCommons; Q99697; -. DR Reactome; R-HSA-8866906; TFAP2 (AP-2) family regulates transcription of other transcription factors. DR SignaLink; Q99697; -. DR SIGNOR; Q99697; -. DR BioGRID-ORCS; 5308; 14 hits in 1172 CRISPR screens. DR ChiTaRS; PITX2; human. DR EvolutionaryTrace; Q99697; -. DR GeneWiki; PITX2; -. DR GenomeRNAi; 5308; -. DR Pharos; Q99697; Tbio. DR PRO; PR:Q99697; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q99697; Protein. DR Bgee; ENSG00000164093; Expressed in gingiva and 121 other cell types or tissues. DR ExpressionAtlas; Q99697; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0051219; F:phosphoprotein binding; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:BHF-UCL. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL. DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central. DR GO; GO:0043010; P:camera-type eye development; IMP:BHF-UCL. DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0035993; P:deltoid tuberosity development; IMP:BHF-UCL. DR GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL. DR GO; GO:0060971; P:embryonic heart tube left/right pattern formation; ISS:BHF-UCL. DR GO; GO:0035315; P:hair cell differentiation; IC:BHF-UCL. DR GO; GO:0061072; P:iris morphogenesis; IMP:BHF-UCL. DR GO; GO:0070986; P:left/right axis specification; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0042476; P:odontogenesis; IMP:BHF-UCL. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0060127; P:prolactin secreting cell differentiation; TAS:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0060126; P:somatotropin secreting cell differentiation; TAS:BHF-UCL. DR GO; GO:0048536; P:spleen development; ISS:BHF-UCL. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR016233; Homeobox_Pitx/unc30. DR InterPro; IPR003654; OAR_dom. DR PANTHER; PTHR45882:SF4; PITUITARY HOMEOBOX 2; 1. DR PANTHER; PTHR45882; PITUITARY HOMEOBOX HOMOLOG PTX1; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF03826; OAR; 1. DR PIRSF; PIRSF000563; Homeobox_protein_Pitx/Unc30; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS50803; OAR; 1. DR Genevisible; Q99697; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein; KW Disease variant; DNA-binding; Homeobox; Nucleus; Peters anomaly; KW Phosphoprotein; Reference proteome. FT CHAIN 1..317 FT /note="Pituitary homeobox 2" FT /id="PRO_0000049223" FT DNA_BIND 85..144 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 35..99 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 279..292 FT /note="OAR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138" FT MOTIF 285..289 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 35..83 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 90 FT /note="Phosphothreonine; by PKB/AKT2" FT /evidence="ECO:0000250" FT VAR_SEQ 1..61 FT /note="METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSPESRKEAASSKF FT FPRQHPGAN -> MNCMKGPLHLEHRAAGTKLSAVSSSSCHHPQPLAMASVLAPGQPRS FT LDSSKHRLEVHTISDTSSPEAA (in isoform PTX2C)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9539779" FT /id="VSP_002260" FT VAR_SEQ 16..61 FT /note="Missing (in isoform PTX2A)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9539779" FT /id="VSP_002261" FT VARIANT 100 FT /note="L -> Q (in RIEG1; dbSNP:rs104893857)" FT /evidence="ECO:0000269|PubMed:8944018" FT /id="VAR_003763" FT VARIANT 108 FT /note="R -> H (in RDC; results in 25% loss of FT transactivation activity; dbSNP:rs104893862)" FT /evidence="ECO:0000269|PubMed:15591271, FT ECO:0000269|PubMed:22224469" FT /id="VAR_035027" FT VARIANT 110 FT /note="P -> L (in RIEG1; dbSNP:rs1057519484)" FT /evidence="ECO:0000269|PubMed:12381896, FT ECO:0000269|PubMed:16936096" FT /id="VAR_058735" FT VARIANT 110 FT /note="P -> R (in RIEG1)" FT /evidence="ECO:0000269|PubMed:16936096" FT /id="VAR_058736" FT VARIANT 114 FT /note="T -> P (in RIEG1; dbSNP:rs104893858)" FT /evidence="ECO:0000269|PubMed:8944018" FT /id="VAR_003764" FT VARIANT 115 FT /note="R -> H (in ASGD4; dbSNP:rs104893861)" FT /evidence="ECO:0000269|PubMed:9618168" FT /id="VAR_003765" FT VARIANT 128..134 FT /note="Missing (in RIEG1; more than 100-fold reduction in FT DNA binding activity as well as no detectable FT transactivation activity)" FT /id="VAR_035028" FT VARIANT 129 FT /note="V -> L (in RIEG1; more than 200% increase in FT transactivation activity; dbSNP:rs121909249)" FT /evidence="ECO:0000269|PubMed:11487566" FT /id="VAR_035029" FT VARIANT 130 FT /note="R -> W (in ASGD4; dbSNP:rs121909248)" FT /evidence="ECO:0000269|PubMed:9437321" FT /id="VAR_003762" FT VARIANT 134 FT /note="K -> E (in RIEG1; dbSNP:rs387906810)" FT /evidence="ECO:0000269|PubMed:10937553" FT /id="VAR_058737" FT VARIANT 136 FT /note="R -> C (in RIEG1)" FT /evidence="ECO:0000269|PubMed:10937553, FT ECO:0000269|PubMed:12381896" FT /id="VAR_058738" FT VARIANT 137 FT /note="R -> P (in RIEG1; dbSNP:rs104893859)" FT /evidence="ECO:0000269|PubMed:8944018" FT /id="VAR_003766" FT VARIANT 151 FT /note="L -> V (in RIEG1)" FT /evidence="ECO:0000269|PubMed:12381896" FT /id="VAR_058739" FT VARIANT 154 FT /note="N -> T (in RIEG1)" FT /evidence="ECO:0000269|PubMed:12381896" FT /id="VAR_058740" FT VARIANT 179..317 FT /note="Missing (in RIEG1)" FT /evidence="ECO:0000269|PubMed:8944018" FT /id="VAR_088641" FT CONFLICT 13 FT /note="V -> L (in Ref. 1 and 3)" FT /evidence="ECO:0000305" FT CONFLICT 99 FT /note="E -> Q (in Ref. 1; AAC16257)" FT /evidence="ECO:0000305" FT CONFLICT 127 FT /note="A -> T (in Ref. 4; BAF84280)" FT /evidence="ECO:0000305" FT CONFLICT 301 FT /note="N -> K (in Ref. 1 and 3)" FT /evidence="ECO:0000305" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:2L7M" FT STRAND 90..92 FT /evidence="ECO:0007829|PDB:2L7M" FT HELIX 94..106 FT /evidence="ECO:0007829|PDB:2L7F" FT HELIX 112..122 FT /evidence="ECO:0007829|PDB:2L7F" FT HELIX 126..141 FT /evidence="ECO:0007829|PDB:2L7F" FT VARIANT Q99697-3:58 FT /note="F -> L (in ASGD4)" FT /evidence="ECO:0000269|PubMed:20881294" FT /id="VAR_082833" SQ SEQUENCE 317 AA; 35370 MW; 00853AFDBA4433CB CRC64; METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PESRKEAASS KFFPRQHPGA NEKDKSQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL EATFQRNRYP DMSTREEIAV WTNLTEARVR VWFKNRRAKW RKRERNQQAE LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA AKGLTSASLS TKSFPFFNSM NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN SLNNLNNLSS PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ NPASNLSACQ YAVDRPV //