PITX2_HUMAN
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 03-AUG-2022, entry version 220.
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;
GN Name=PITX2 {ECO:0000312|HGNC:HGNC:9005}; Synonyms=ARP1, RGS, RIEG, RIEG1;
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 AND PRO-137.
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 ARG-128--134-LYS DEL AND LEU-129, AND CHARACTERIZATION OF
RP VARIANTS RIEG1 ARG-128--134-LYS 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: Controls cell proliferation in a tissue-specific manner and
CC is involved in morphogenesis. During embryonic development, exerts a
CC role in the expansion of muscle progenitors. May play a role in the
CC proper localization of asymmetric organs such as the heart and stomach.
CC Isoform PTX2C is involved in left-right asymmetry the developing embryo
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PITX2. {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; Q9Y458: TBX22; NbExp=3; IntAct=EBI-12138495, EBI-6427217;
CC Q99697-2; Q96LM6: TEX37; NbExp=3; IntAct=EBI-12138495, EBI-743976;
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.
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: Phosphorylation at Thr-90 impairs its association with the CCND1
CC mRNA-stabilizing complex thus shortening the half-life of CCND1.
CC {ECO:0000250}.
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}.
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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; 84.
DR CORUM; Q99697; -.
DR IntAct; Q99697; 60.
DR MINT; Q99697; -.
DR STRING; 9606.ENSP00000304169; -.
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; Q99697; -.
DR PeptideAtlas; Q99697; -.
DR PRIDE; Q99697; -.
DR ProteomicsDB; 78403; -. [Q99697-1]
DR ProteomicsDB; 78404; -. [Q99697-2]
DR ProteomicsDB; 78405; -. [Q99697-3]
DR Antibodypedia; 15459; 308 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 CTD; 5308; -.
DR DisGeNET; 5308; -.
DR GeneCards; PITX2; -.
DR HGNC; HGNC:9005; PITX2.
DR HPA; ENSG00000164093; Tissue enhanced (placenta, skeletal muscle, 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; NSMRNPL; -.
DR OrthoDB; 1432356at2759; -.
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; 11 hits in 1094 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 119 other tissues.
DR ExpressionAtlas; Q99697; baseline and differential.
DR Genevisible; Q99697; HS.
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; IC: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:0061325; P:cell proliferation 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: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:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
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 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 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; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Developmental protein; Disease variant;
KW DNA-binding; Homeobox; Nucleus; Peters anomaly; Phosphoprotein;
KW 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 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
