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Homeobox protein Nkx-3.1 (Homeobox protein NK-3 homolog A)

 NKX31_MOUSE             Reviewed;         237 AA.
P97436; O09087;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
01-MAY-1997, sequence version 1.
18-JUL-2018, entry version 156.
RecName: Full=Homeobox protein Nkx-3.1;
AltName: Full=Homeobox protein NK-3 homolog A;
Name=Nkx3-1; Synonyms=Nkx-3.1, Nkx3a;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Prostate;
PubMed=8943214; DOI=10.1074/jbc.271.50.31779;
Bieberich C.J., Fujita K., He W.-W., Jay G.;
"Prostate-specific and androgen-dependent expression of a novel
homeobox gene.";
J. Biol. Chem. 271:31779-31782(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Swiss Webster; TISSUE=Embryo;
PubMed=9142502;
DOI=10.1002/(SICI)1097-0177(199705)209:1<127::AID-AJA12>3.0.CO;2-Z;
Sciavolino P.J., Abrams E.W., Yang L., Austenberg L.P., Shen M.M.,
Abate-Shen C.;
"Tissue-specific expression of murine Nkx3.1 in the male urogenital
system.";
Dev. Dyn. 209:127-138(1997).
[3]
FUNCTION AS TUMOR SUPPRESSOR.
PubMed=12036903;
Kim M.J., Bhatia-Gaur R., Banach-Petrosky W.A., Desai N., Wang Y.,
Hayward S.W., Cunha G.R., Cardiff R.D., Shen M.M., Abate-Shen C.;
"Nkx3.1 mutant mice recapitulate early stages of prostate
carcinogenesis.";
Cancer Res. 62:2999-3004(2002).
-!- FUNCTION: Transcription factor, which binds preferentially the
consensus sequence 5'-TAAGT[AG]-3' and can behave as a
transcriptional repressor (By similarity). Plays an important role
in normal prostate development, regulating proliferation of
glandular epithelium and in the formation of ducts in prostate.
Acts as a tumor suppressor controlling prostate carcinogenesis, as
shown by the ability to suppress growth and tumorigenicity of
prostate carcinoma cells. Plays a role in the formation of minor
salivary glands (particularly palatine and lingual glands).
Essential for appropriate differentiation and secretory function
of the bulbourethral gland. {ECO:0000250,
ECO:0000269|PubMed:12036903}.
-!- SUBUNIT: Interacts with serum response factor (SRF). Interacts
with SPDEF (By similarity). Interacts with WDR77 (By similarity).
Interacts with TOPORS which polyubiquitinates NKX3-1 and induces
its proteasomal degradation (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108}.
-!- TISSUE SPECIFICITY: Expressed mostly in the male urogenital tract,
with highest expression in the epithelial cells lining the ducts
of anterior, dorsolateral and ventral prostate and in the
bulbourethral gland, and much lower in the seminal vesicle and the
testis. Expression in the prostate increases during sexual
maturation and is drastically reduced following castration.
Expressed also in brain (hippocampus and external granular layer
of the cerebral cortex), kidney (intralobular arteries), thymus
and adrenal and salivary glands.
-!- DEVELOPMENTAL STAGE: Early marker of the sclerotome and of a
subset of vascular smooth muscle cells, expressed also in
outgrowths of epithelial cells, in ectodermal epithelial cells and
in restricted regions of the central nervous system. Detected
first at 7.5 dpc in the paraxial mesoderm adjacent to the neural
fold. At 8.5 dpc, segmental expression in the first 8 or 9
somites. Expression proceeds caudally in parallel with somite
maturation and is restricted to the sclerotome. As the somites
mature, expression moves away from the axial structures, becomes
transiently restricted to a subset of early myotomal cells at the
dorsal medial lip and is subsequently down-regulated. At 10.5 dpc,
expressed only in the most caudal immature somites. At 9.5 dpc,
present in the dorsal aorta. At 11.5 dpc, restricted to the
vascular smooth muscle cells of caudal region of the dorsal aorta.
At 12.5 dpc, expressed in the distal epithelium of the tongue and
in Rathke pouch (anterior pituitary). By 13.5 dpc, also detected
in tooth buds. Expression in the abdominal aorta continues through
11.5 to 15.5 dpc. Detected in the vertebral vessels at 12.5 dpc,
in the carotid vessel at 13.5 dpc and in arcuate and interlobular
arteries of the kidney at 15.5 dpc. In neonates, present in
palatine glands, epithelial root sheath of the tooth and
epithelial hair sheath. In the nervous system of neonates,
expressed in the olfactory lobe, olfactory epithelial cells and
cerebellar cortex. Expressed in the male urogenital system during
late embryogenesis: at day 14.5, expressed in the outbuddings of
the pelvic region of the urogenital sinus, and, at lower levels,
in the prospective urethra. Expression is confined to the
epithelial cells that are invaginating into the surrounding
mesenchyme, with highest levels at the leading edge. At 17.5 dpc,
present in the developing ventral, dorsolateral and anterior
prostatic buds, in the nascent bulbourethral glands, as well as in
the epithelial ducts that join the glands to the prospective
urethra. During postnatal growth and morphogenesis of the
prostate, high expression is maintain at sites of ductal outgrowth
and branching. In the developing testis, detected at 14.5 and 17.5
dpc in the medullary cords, which form seminiferous tubules.
-!- INDUCTION: By androgens. During embryonic development, induced and
maintained by sonic hedgehog in pre-somitic mesoderm, in immature
somites and in urogenital sinus, but not in the other expression
domains.
-!- PTM: Ubiquitinated by TOPORS; monoubiquitinated at several
residues and also polyubiquitinated on single residues.
{ECO:0000250}.
-!- SIMILARITY: Belongs to the NK-3 homeobox family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; U73460; AAC52956.1; -; mRNA.
EMBL; U88542; AAB58025.1; -; mRNA.
CCDS; CCDS27237.1; -.
RefSeq; NP_035051.1; NM_010921.3.
UniGene; Mm.3520; -.
ProteinModelPortal; P97436; -.
SMR; P97436; -.
BioGrid; 201781; 2.
STRING; 10090.ENSMUSP00000022646; -.
PhosphoSitePlus; P97436; -.
PaxDb; P97436; -.
PRIDE; P97436; -.
Ensembl; ENSMUST00000022646; ENSMUSP00000022646; ENSMUSG00000022061.
GeneID; 18095; -.
KEGG; mmu:18095; -.
UCSC; uc007umd.1; mouse.
CTD; 4824; -.
MGI; MGI:97352; Nkx3-1.
eggNOG; KOG0842; Eukaryota.
eggNOG; ENOG410XR21; LUCA.
GeneTree; ENSGT00910000144003; -.
HOGENOM; HOG000231923; -.
HOVERGEN; HBG006689; -.
InParanoid; P97436; -.
KO; K09348; -.
OMA; QTAKQPQ; -.
OrthoDB; EOG091G0RNV; -.
PhylomeDB; P97436; -.
TreeFam; TF315720; -.
PRO; PR:P97436; -.
Proteomes; UP000000589; Chromosome 14.
Bgee; ENSMUSG00000022061; -.
CleanEx; MM_NKX3-1; -.
ExpressionAtlas; P97436; baseline and differential.
Genevisible; P97436; MM.
GO; GO:0005622; C:intracellular; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0004882; F:androgen receptor activity; ISS:UniProtKB.
GO; GO:0001047; F:core promoter binding; ISO:MGI.
GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IEA:Ensembl.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0003700; F:DNA binding transcription factor activity; IDA:MGI.
GO; GO:0030284; F:estrogen receptor activity; ISS:UniProtKB.
GO; GO:0030331; F:estrogen receptor binding; ISS:UniProtKB.
GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
GO; GO:0097162; F:MADS box domain binding; IDA:UniProtKB.
GO; GO:0030295; F:protein kinase activator activity; ISS:UniProtKB.
GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IDA:MGI.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:MGI.
GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
GO; GO:0030521; P:androgen receptor signaling pathway; ISS:UniProtKB.
GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IMP:MGI.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
GO; GO:0035690; P:cellular response to drug; IEA:Ensembl.
GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISS:UniProtKB.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
GO; GO:0035907; P:dorsal aorta development; IEP:UniProtKB.
GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IMP:MGI.
GO; GO:0007507; P:heart development; IEP:BHF-UCL.
GO; GO:0035260; P:internal genitalia morphogenesis; TAS:BHF-UCL.
GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
GO; GO:0071850; P:mitotic cell cycle arrest; ISO:MGI.
GO; GO:0008285; P:negative regulation of cell proliferation; IGI:MGI.
GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
GO; GO:0071899; P:negative regulation of estrogen receptor binding; ISS:UniProtKB.
GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:MGI.
GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
GO; GO:0060037; P:pharyngeal system development; IEP:BHF-UCL.
GO; GO:2000836; P:positive regulation of androgen secretion; ISS:UniProtKB.
GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:MGI.
GO; GO:0010942; P:positive regulation of cell death; ISS:UniProtKB.
GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0030850; P:prostate gland development; IEP:UniProtKB.
GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
GO; GO:0033574; P:response to testosterone; IMP:UniProtKB.
GO; GO:0007431; P:salivary gland development; IMP:MGI.
GO; GO:0001756; P:somitogenesis; IEP:BHF-UCL.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0001655; P:urogenital system development; IEP:UniProtKB.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Complete proteome; Developmental protein; DNA-binding; Homeobox;
Nucleus; Reference proteome; Repressor; Transcription;
Transcription regulation; Tumor suppressor; Ubl conjugation.
CHAIN 1 237 Homeobox protein Nkx-3.1.
/FTId=PRO_0000048946.
DNA_BIND 125 184 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
SEQUENCE 237 AA; 26824 MW; 4B074387F3BA1223 CRC64;
MLRVAEPREP RVEAGGRSPW AAPPTQSKRL TSFLIQDILR DRAERHGGHS GNPQHSPDPR
RDSAPEPDKA GGRGVAPEDP PSIRHSPAET PTEPESDAHF ETYLLDCEHN PGDLASAPQV
TKQPQKRSRA AFSHTQVIEL ERKFSHQKYL SAPERAHLAK NLKLTETQVK IWFQNRRYKT
KRKQLSEDLG VLEKNSPLSL PALKDDSLPS TSLVSVYTSY PYYPYLYCLG SWHPSFW


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