PITX3_MOUSE
ID PITX3_MOUSE Reviewed; 302 AA.
AC O35160; Q0VB03;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Pituitary homeobox 3;
DE AltName: Full=Homeobox protein PITX3;
DE AltName: Full=Paired-like homeodomain transcription factor 3;
GN Name=Pitx3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo, and Embryonic carcinoma;
RX PubMed=9328475; DOI=10.1093/hmg/6.12.2109;
RA Semina E.V., Reiter R.S., Murray J.C.;
RT "Isolation of a new homeobox gene belonging to the Pitx/Rieg family:
RT expression during lens development and mapping to the aphakia region on
RT mouse chromosome 19.";
RL Hum. Mol. Genet. 6:2109-2116(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Testis;
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 [3]
RP DEVELOPMENTAL STAGE.
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 [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=15950611; DOI=10.1016/j.ydbio.2005.03.028;
RA Maxwell S.L., Ho H.Y., Kuehner E., Zhao S., Li M.;
RT "Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra
RT and identifies a subgroup of mesencephalic dopaminergic progenitor neurons
RT during mouse development.";
RL Dev. Biol. 282:467-479(2005).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17184956; DOI=10.1016/j.ijdevneu.2006.11.003;
RA Messmer K., Remington M.P., Skidmore F., Fishman P.S.;
RT "Induction of tyrosine hydroxylase expression by the transcription factor
RT Pitx3.";
RL Int. J. Dev. Neurosci. 25:29-37(2007).
RN [6]
RP FUNCTION, AND DISEASE.
RX PubMed=19334279; DOI=10.1002/dvdy.21924;
RA Medina-Martinez O., Shah R., Jamrich M.;
RT "Pitx3 controls multiple aspects of lens development.";
RL Dev. Dyn. 238:2193-2201(2009).
RN [7]
RP FUNCTION, AND INTERACTION WITH SFPQ.
RX PubMed=19144721; DOI=10.1242/dev.029769;
RA Jacobs F.M., van Erp S., van der Linden A.J., von Oerthel L., Burbach J.P.,
RA Smidt M.P.;
RT "Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation
RT through release of SMRT-mediated repression.";
RL Development 136:531-540(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=19007884; DOI=10.1016/j.mod.2008.10.007;
RA Ho H.Y., Chang K.H., Nichols J., Li M.;
RT "Homeodomain protein Pitx3 maintains the mitotic activity of lens
RT epithelial cells.";
RL Mech. Dev. 126:18-29(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.
CC {ECO:0000269|PubMed:15950611, ECO:0000269|PubMed:17184956,
CC ECO:0000269|PubMed:19007884, ECO:0000269|PubMed:19144721,
CC ECO:0000269|PubMed:19334279}.
CC -!- SUBUNIT: Interacts with SFPQ. {ECO:0000269|PubMed:19144721}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000255|PROSITE-ProRule:PRU00138, ECO:0000269|PubMed:17184956}.
CC -!- TISSUE SPECIFICITY: Highly expressed in developing eye lens. Expression
CC is restricted to the substantia nigra and ventral tegmental area in the
CC midbrain. {ECO:0000269|PubMed:15950611, ECO:0000269|PubMed:19007884}.
CC -!- DEVELOPMENTAL STAGE: First visible in 10.5 dpc embryos where expression
CC is confined to the lens vesicles. Between 11.5 dpc and 12.5 dpc,
CC expressed in both the lens epithelium and differentiating primary fiber
CC cells. In the late fetal stage after the lens is formed, primarily
CC found in the lens epithelium and the lens equator region where lens
CC epithelial cells exit from the cell cycle and differentiate into fiber
CC cells (at protein level). First expressed in the eye at 10 dpc embryos.
CC Throughout eye development, expressed in the lens placode and forming
CC lens pit. From 12 dpc, also detected in the midbrain region, tongue,
CC incisor primordia, condensing mesenchyme around the sternum and
CC vertebrae and in the head muscles. {ECO:0000269|PubMed:19007884,
CC ECO:0000269|PubMed:9620774}.
CC -!- DISEASE: Note=Mutations in Pitx3 appear to be the cause of the aphakia
CC (ak) phenotype, a recessive homozygous disease characterized by small
CC eyes and closed eyelids. {ECO:0000269|PubMed:19334279}.
CC -!- DISRUPTION PHENOTYPE: Mice show loss of nascent substantia nigra
CC dopaminergic neurons at the beginning of their final differentiation
CC and a loss of tyrosine hydroxylase (TH) expression specifically in the
CC substantia nigra neurons. {ECO:0000269|PubMed:15950611}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AF005772; AAB87380.1; -; mRNA.
DR EMBL; BC120844; AAI20845.1; -; mRNA.
DR EMBL; BC137810; AAI37811.1; -; mRNA.
DR CCDS; CCDS29872.1; -.
DR RefSeq; NP_032878.1; NM_008852.4.
DR AlphaFoldDB; O35160; -.
DR BMRB; O35160; -.
DR SMR; O35160; -.
DR BioGRID; 202188; 1.
DR IntAct; O35160; 1.
DR STRING; 10090.ENSMUSP00000026259; -.
DR PhosphoSitePlus; O35160; -.
DR PaxDb; O35160; -.
DR PRIDE; O35160; -.
DR ProteomicsDB; 289587; -.
DR Antibodypedia; 18010; 212 antibodies from 35 providers.
DR DNASU; 18742; -.
DR Ensembl; ENSMUST00000026259; ENSMUSP00000026259; ENSMUSG00000025229.
DR GeneID; 18742; -.
DR KEGG; mmu:18742; -.
DR UCSC; uc008hsl.1; mouse.
DR CTD; 5309; -.
DR MGI; MGI:1100498; Pitx3.
DR VEuPathDB; HostDB:ENSMUSG00000025229; -.
DR eggNOG; KOG0486; Eukaryota.
DR GeneTree; ENSGT00940000161801; -.
DR HOGENOM; CLU_030301_0_0_1; -.
DR InParanoid; O35160; -.
DR OMA; PLPEHSC; -.
DR OrthoDB; 1432356at2759; -.
DR PhylomeDB; O35160; -.
DR TreeFam; TF351940; -.
DR BioGRID-ORCS; 18742; 0 hits in 75 CRISPR screens.
DR PRO; PR:O35160; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O35160; protein.
DR Bgee; ENSMUSG00000025229; Expressed in lens of camera-type eye and 67 other tissues.
DR ExpressionAtlas; O35160; baseline and differential.
DR Genevisible; O35160; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:1990792; P:cellular response to glial cell derived neurotrophic factor; IEA:Ensembl.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IDA:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:UniProtKB.
DR GO; GO:0070306; P:lens fiber cell differentiation; IMP:UniProtKB.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IMP:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0030901; P:midbrain development; IMP:UniProtKB.
DR GO; GO:0014014; P:negative regulation of gliogenesis; ISO:MGI.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISO:MGI.
DR GO; GO:0048666; P:neuron development; IMP:MGI.
DR GO; GO:1904935; P:positive regulation of cell proliferation in midbrain; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
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; IDA: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; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..302
FT /note="Pituitary homeobox 3"
FT /id="PRO_0000049230"
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"
SQ SEQUENCE 302 AA; 31715 MW; EB6EF6863B349264 CRC64;
MEFGLLGEAE ARSPALSLSD AGTPHPPLPE HGCKGQEHSD SEKASASLPG GSPEDGSLKK
KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN LTEARVRVWF KNRRAKWRKR
ERSQQAELCK GGFAAPLGGL VPPYEEVYPG YSYGNWPPKA LAPPLAAKTF PFAFNSVNVG
PLASQPVFSP PSSIAASMVP SAAAAPGTVP GPGALQGLGG APPGLAPAAV SSGAVSCPYA
SAAAAAAAAA SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVPGPPPAAN LSPCQYAVER
PV
