PITX3_HUMAN
ID PITX3_HUMAN Reviewed; 302 AA.
AC O75364; Q5VZL2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Pituitary homeobox 3;
DE AltName: Full=Homeobox protein PITX3;
DE AltName: Full=Paired-like homeodomain transcription factor 3;
GN Name=PITX3; Synonyms=PTX3;
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], VARIANT CTRCT11 ASN-13, AND INVOLVEMENT IN
RP ASGD1.
RC TISSUE=Craniofacial;
RX PubMed=9620774; DOI=10.1038/527;
RA Semina E.V., Ferrell R.E., Mintz-Hittner H.A., Bitoun P., Alward W.L.M.,
RA Reiter R.S., Funkhauser C., Daack-Hirsch S., Murray J.C.;
RT "A novel homeobox gene PITX3 is mutated in families with autosomal-dominant
RT cataracts and ASMD.";
RL Nat. Genet. 19:167-170(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [4]
RP INVOLVEMENT IN CTRCT11.
RX PubMed=15286169; DOI=10.1136/jmg.2004.020289;
RA Berry V., Yang Z., Addison P.K., Francis P.J., Ionides A., Karan G.,
RA Jiang L., Lin W., Hu J., Yang R., Moore A., Zhang K., Bhattacharya S.S.;
RT "Recurrent 17 bp duplication in PITX3 is primarily associated with
RT posterior polar cataract (CPP4).";
RL J. Med. Genet. 41:E109-E109(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
CC -!- FUNCTION: Transcriptional regulator which is important for the
CC differentiation and maintenance of meso-diencephalic dopaminergic
CC (mdDA) neurons during development. In addition to its importance during
CC development, it also has roles in the long-term survival and
CC maintenance of the mdDA neurons. Activates NR4A2/NURR1-mediated
CC transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are
CC essential for development of mdDA neurons. Acts by decreasing the
CC interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts
CC through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1
CC target genes in a repressed deacetylated state. Essential for the
CC normal lens development and differentiation. Plays a critical role in
CC the maintenance of mitotic activity of lens epithelial cells, fiber
CC cell differentiation and in the control of the temporal and spatial
CC activation of fiber cell-specific crystallins. Positively regulates
CC FOXE3 expression and negatively regulates PROX1 in the anterior lens
CC epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2
CC and thus maintains lens epithelial cells in cell cycle (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with SFPQ. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000255|PROSITE-ProRule:PRU00138}.
CC -!- TISSUE SPECIFICITY: Highly expressed in developing eye lens.
CC -!- DISEASE: Anterior segment dysgenesis 1 (ASGD1) [MIM:107250]: 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. {ECO:0000269|PubMed:9620774}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Cataract 11, multiple types (CTRCT11) [MIM:610623]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. CTRCT11 includes posterior polar cataract, among
CC others. Posterior polar cataract is a subcapsular opacity, usually
CC disk-shaped, located at the back of the lens. Some CTRCT11 patients can
CC present a severe phenotype including microphthalmia and neurological
CC dysfunction. {ECO:0000269|PubMed:15286169, ECO:0000269|PubMed:9620774}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AF041339; AAC24502.1; -; mRNA.
DR EMBL; AL160011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011642; AAH11642.1; -; mRNA.
DR CCDS; CCDS7532.1; -.
DR RefSeq; NP_005020.1; NM_005029.3.
DR AlphaFoldDB; O75364; -.
DR BMRB; O75364; -.
DR SMR; O75364; -.
DR BioGRID; 111326; 4.
DR STRING; 9606.ENSP00000359019; -.
DR iPTMnet; O75364; -.
DR PhosphoSitePlus; O75364; -.
DR BioMuta; PITX3; -.
DR jPOST; O75364; -.
DR MassIVE; O75364; -.
DR MaxQB; O75364; -.
DR PaxDb; O75364; -.
DR PeptideAtlas; O75364; -.
DR PRIDE; O75364; -.
DR Antibodypedia; 18010; 212 antibodies from 35 providers.
DR DNASU; 5309; -.
DR Ensembl; ENST00000370002.8; ENSP00000359019.3; ENSG00000107859.10.
DR Ensembl; ENST00000539804.1; ENSP00000439383.1; ENSG00000107859.10.
DR GeneID; 5309; -.
DR KEGG; hsa:5309; -.
DR MANE-Select; ENST00000370002.8; ENSP00000359019.3; NM_005029.4; NP_005020.1.
DR UCSC; uc001kuu.2; human.
DR CTD; 5309; -.
DR DisGeNET; 5309; -.
DR GeneCards; PITX3; -.
DR HGNC; HGNC:9006; PITX3.
DR HPA; ENSG00000107859; Group enriched (brain, skeletal muscle, tongue).
DR MalaCards; PITX3; -.
DR MIM; 107250; phenotype.
DR MIM; 602669; gene.
DR MIM; 610623; phenotype.
DR neXtProt; NX_O75364; -.
DR OpenTargets; ENSG00000107859; -.
DR Orphanet; 162; Cataract-glaucoma syndrome.
DR Orphanet; 98993; Early-onset posterior polar cataract.
DR PharmGKB; PA33340; -.
DR VEuPathDB; HostDB:ENSG00000107859; -.
DR eggNOG; KOG0486; Eukaryota.
DR GeneTree; ENSGT00940000161801; -.
DR HOGENOM; CLU_030301_0_0_1; -.
DR InParanoid; O75364; -.
DR OMA; PLPEHSC; -.
DR OrthoDB; 1432356at2759; -.
DR PhylomeDB; O75364; -.
DR TreeFam; TF351940; -.
DR PathwayCommons; O75364; -.
DR SignaLink; O75364; -.
DR SIGNOR; O75364; -.
DR BioGRID-ORCS; 5309; 11 hits in 1094 CRISPR screens.
DR GeneWiki; PITX3; -.
DR GenomeRNAi; 5309; -.
DR Pharos; O75364; Tbio.
DR PRO; PR:O75364; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O75364; protein.
DR Bgee; ENSG00000107859; Expressed in hindlimb stylopod muscle and 62 other tissues.
DR Genevisible; O75364; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:1990792; P:cellular response to glial cell derived neurotrophic factor; IEA:Ensembl.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; ISS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
DR GO; GO:0014014; P:negative regulation of gliogenesis; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:1904935; P:positive regulation of cell proliferation in midbrain; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
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:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:1904313; P:response to methamphetamine hydrochloride; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
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 Activator; Cataract; Developmental protein; Disease variant; DNA-binding;
KW Homeobox; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..302
FT /note="Pituitary homeobox 3"
FT /id="PRO_0000049229"
FT DNA_BIND 62..121
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 262..275
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT MOTIF 268..272
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P81062"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P81062"
FT VARIANT 13
FT /note="S -> N (in CTRCT11; dbSNP:rs104894175)"
FT /evidence="ECO:0000269|PubMed:9620774"
FT /id="VAR_003767"
SQ SEQUENCE 302 AA; 31832 MW; 1E5259206ABC2E87 CRC64;
MEFGLLSEAE ARSPALSLSD AGTPHPQLPE HGCKGQEHSD SEKASASLPG GSPEDGSLKK
KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN LTEARVRVWF KNRRAKWRKR
ERSQQAELCK GSFAAPLGGL VPPYEEVYPG YSYGNWPPKA LAPPLAAKTF PFAFNSVNVG
PLASQPVFSP PSSIAASMVP SAAAAPGTVP GPGALQGLGG GPPGLAPAAV SSGAVSCPYA
SAAAAAAAAA SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVHGPPPAAN LSPCQYAVER
PV
