PITX3_RAT
ID PITX3_RAT Reviewed; 302 AA.
AC P81062;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 148.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hypothalamus;
RX PubMed=9371841; DOI=10.1073/pnas.94.24.13305;
RA Smidt M.P., van Shaick H.S.A., Lanctot C., Tremblay J.T., Cox J.J.,
RA van der Kleij A.A.M., Wolterink G., Drouin J., Burbach J.P.H.;
RT "A homeodomain gene Ptx3 has highly restricted brain expression in
RT mesencephalic dopaminergic neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13305-13310(1997).
RN [2]
RP SEQUENCE REVISION TO 66; 108; 122 AND 132-135.
RA Smidt M.P.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-57, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=18951485; DOI=10.1002/jnr.21911;
RA Katunar M.R., Saez T., Brusco A., Antonelli M.C.;
RT "Immunocytochemical expression of dopamine-related transcription factors
RT Pitx3 and Nurr1 in prenatally stressed adult rats.";
RL J. Neurosci. Res. 87:1014-1022(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.
CC -!- TISSUE SPECIFICITY: Expression is restricted to the substantia nigra
CC and ventral tegmental area in the midbrain. Expression increases in
CC prenatally stressed adult offspring in the ventral tegmental area,
CC whereas no changes are observed in the substantia nigra area (at
CC protein level). {ECO:0000269|PubMed:18951485}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AJ011005; CAA09455.2; -; mRNA.
DR RefSeq; NP_062120.1; NM_019247.1.
DR RefSeq; XP_006231540.1; XM_006231478.2.
DR AlphaFoldDB; P81062; -.
DR BMRB; P81062; -.
DR SMR; P81062; -.
DR STRING; 10116.ENSRNOP00000026013; -.
DR iPTMnet; P81062; -.
DR PhosphoSitePlus; P81062; -.
DR PaxDb; P81062; -.
DR DNASU; 29609; -.
DR Ensembl; ENSRNOT00000026013; ENSRNOP00000026013; ENSRNOG00000019194.
DR GeneID; 29609; -.
DR KEGG; rno:29609; -.
DR UCSC; RGD:3332; rat.
DR CTD; 5309; -.
DR RGD; 3332; Pitx3.
DR eggNOG; KOG0486; Eukaryota.
DR GeneTree; ENSGT00940000161801; -.
DR HOGENOM; CLU_030301_0_0_1; -.
DR InParanoid; P81062; -.
DR OMA; PLPEHSC; -.
DR OrthoDB; 1432356at2759; -.
DR PhylomeDB; P81062; -.
DR TreeFam; TF351940; -.
DR PRO; PR:P81062; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019194; Expressed in skeletal muscle tissue and 4 other tissues.
DR Genevisible; P81062; RN.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:1990792; P:cellular response to glial cell derived neurotrophic factor; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; ISS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
DR GO; GO:0014014; P:negative regulation of gliogenesis; IDA:RGD.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IDA:RGD.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:1904935; P:positive regulation of cell proliferation in midbrain; IDA:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
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; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:1904313; P:response to methamphetamine hydrochloride; IEP:RGD.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
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_0000049231"
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:0007744|PubMed:16641100"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
SQ SEQUENCE 302 AA; 31729 MW; DE0E81863C44E714 CRC64;
MEFGLLGEAE ARSPALSLSD AGTPHPPLPE HGCKGQEHSD SEKASASLPG GSPEDGSLKK
KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN LTEARVRVWF KNRRAKWRKR
ERSQQAELCK GGFAAPLGGL VPPYEEVYPG YTYGNWPPKA LAPPLAAKTF PFAFNSVNVG
PLASQPVFSP PSSIAASMVP SAAAAPGTVP GPGALQGLGG APPGLAPAAV SSGAVSCPYA
SAAAAAAAAA SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVPGPPPAAN LSPCQYAVER
PV
