NKX31_MOUSE
ID NKX31_MOUSE Reviewed; 237 AA.
AC P97436; O09087;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Homeobox protein Nkx-3.1 {ECO:0000303|PubMed:8943214};
DE AltName: Full=Homeobox protein NK-3 homolog A {ECO:0000250|UniProtKB:Q99801};
GN Name=Nkx3-1 {ECO:0000312|MGI:MGI:97352};
GN Synonyms=Nkx-3.1 {ECO:0000303|PubMed:8943214},
GN Nkx3a {ECO:0000250|UniProtKB:Q99801};
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], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Prostate;
RX PubMed=8943214; DOI=10.1074/jbc.271.50.31779;
RA Bieberich C.J., Fujita K., He W.-W., Jay G.;
RT "Prostate-specific and androgen-dependent expression of a novel homeobox
RT gene.";
RL J. Biol. Chem. 271:31779-31782(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Swiss Webster; TISSUE=Embryo;
RX PubMed=9142502;
RX DOI=10.1002/(sici)1097-0177(199705)209:1<127::aid-aja12>3.0.co;2-z;
RA Sciavolino P.J., Abrams E.W., Yang L., Austenberg L.P., Shen M.M.,
RA Abate-Shen C.;
RT "Tissue-specific expression of murine Nkx3.1 in the male urogenital
RT system.";
RL Dev. Dyn. 209:127-138(1997).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10215624; DOI=10.1101/gad.13.8.966;
RA Bhatia-Gaur R., Donjacour A.A., Sciavolino P.J., Kim M., Desai N.,
RA Young P., Norton C.R., Gridley T., Cardiff R.D., Cunha G.R., Abate-Shen C.,
RA Shen M.M.;
RT "Roles for Nkx3.1 in prostate development and cancer.";
RL Genes Dev. 13:966-977(1999).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=10415359; DOI=10.1016/s0925-4773(99)00084-2;
RA Tanaka M., Lyons G.E., Izumo S.;
RT "Expression of the Nkx3.1 homobox gene during pre and postnatal
RT development.";
RL Mech. Dev. 85:179-182(1999).
RN [5]
RP DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=10906459; DOI=10.1016/s0925-4773(00)00355-5;
RA Schneider A., Brand T., Zweigerdt R., Arnold H.;
RT "Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic
RT defects of minor salivary glands: parallels to glandular duct morphogenesis
RT in prostate.";
RL Mech. Dev. 95:163-174(2000).
RN [6]
RP FUNCTION AS TUMOR SUPPRESSOR.
RX PubMed=12036903;
RA Kim M.J., Bhatia-Gaur R., Banach-Petrosky W.A., Desai N., Wang Y.,
RA Hayward S.W., Cunha G.R., Cardiff R.D., Shen M.M., Abate-Shen C.;
RT "Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.";
RL Cancer Res. 62:2999-3004(2002).
RN [7]
RP INTERACTION WITH SRF.
RX PubMed=16814806; DOI=10.1016/j.jmb.2006.05.064;
RA Ju J.H., Maeng J.S., Zemedkun M., Ahronovitz N., Mack J.W., Ferretti J.A.,
RA Gelmann E.P., Gruschus J.M.;
RT "Physical and functional interactions between the prostate suppressor
RT homeoprotein NKX3.1 and serum response factor.";
RL J. Mol. Biol. 360:989-999(2006).
RN [8]
RP INTERACTION WITH FEM1B.
RX PubMed=18816836; DOI=10.1002/dvdy.21694;
RA Wang X., Desai N., Hu Y.P., Price S.M., Abate-Shen C., Shen M.M.;
RT "Mouse Fem1b interacts with the Nkx3.1 homeoprotein and is required for
RT proper male secondary sexual development.";
RL Dev. Dyn. 237:2963-2972(2008).
CC -!- FUNCTION: Transcription factor, which binds preferentially the
CC consensus sequence 5'-TAAGT[AG]-3' and can behave as a transcriptional
CC repressor (By similarity). Plays an important role in normal prostate
CC development, regulating proliferation of glandular epithelium and in
CC the formation of ducts in prostate (PubMed:10215624). Acts as a tumor
CC suppressor controlling prostate carcinogenesis, as shown by the ability
CC to suppress growth and tumorigenicity of prostate carcinoma cells
CC (PubMed:12036903). Plays a role in the formation of minor salivary
CC glands (particularly palatine and lingual glands) (PubMed:10906459).
CC {ECO:0000250|UniProtKB:Q99801, ECO:0000269|PubMed:10215624,
CC ECO:0000269|PubMed:10906459, ECO:0000269|PubMed:12036903}.
CC -!- SUBUNIT: Interacts with serum response factor (SRF) (PubMed:16814806).
CC Interacts with SPDEF. Interacts with WDR77. Interacts with TOPORS which
CC polyubiquitinates NKX3-1 and induces its proteasomal degradation (By
CC similarity). Interacts with FEM1B (PubMed:18816836).
CC {ECO:0000250|UniProtKB:Q99801, ECO:0000269|PubMed:16814806,
CC ECO:0000269|PubMed:18816836}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- TISSUE SPECIFICITY: Expressed mostly in the male urogenital tract, with
CC highest expression in the epithelial cells lining the ducts of
CC anterior, dorsolateral and ventral prostate and in the bulbourethral
CC gland, and much lower in the seminal vesicle and the testis
CC (PubMed:8943214, PubMed:9142502, PubMed:10215624). Expression in the
CC prostate increases during sexual maturation and is drastically reduced
CC following castration. Expressed also in brain (hippocampus and external
CC granular layer of the cerebral cortex), kidney (intralobular arteries),
CC thymus and adrenal and salivary glands (PubMed:8943214,
CC PubMed:9142502). {ECO:0000269|PubMed:10215624,
CC ECO:0000269|PubMed:8943214, ECO:0000269|PubMed:9142502}.
CC -!- DEVELOPMENTAL STAGE: Early marker of the sclerotome and of a subset of
CC vascular smooth muscle cells, expressed also in outgrowths of
CC epithelial cells, in ectodermal epithelial cells and in restricted
CC regions of the central nervous system. Detected first at 7.5 dpc in the
CC paraxial mesoderm adjacent to the neural fold. At 8.5 dpc, segmental
CC expression in the first 8 or 9 somites. Expression proceeds caudally in
CC parallel with somite maturation and is restricted to the sclerotome. As
CC the somites mature, expression moves away from the axial structures,
CC becomes transiently restricted to a subset of early myotomal cells at
CC the dorsal medial lip and is subsequently down-regulated. At 10.5 dpc,
CC expressed only in the most caudal immature somites. At 9.5 dpc, present
CC in the dorsal aorta. At 11.5 dpc, restricted to the vascular smooth
CC muscle cells of caudal region of the dorsal aorta. At 12.5 dpc,
CC expressed in the distal epithelium of the tongue and in Rathke pouch
CC (anterior pituitary). By 13.5 dpc, also detected in tooth buds.
CC Expression in the abdominal aorta continues through 11.5 to 15.5 dpc.
CC Detected in the vertebral vessels at 12.5 dpc, in the carotid vessel at
CC 13.5 dpc and in arcuate and interlobular arteries of the kidney at 15.5
CC dpc. In neonates, present in palatine glands, epithelial root sheath of
CC the tooth and epithelial hair sheath. In the nervous system of
CC neonates, expressed in the olfactory lobe, olfactory epithelial cells
CC and cerebellar cortex. Expressed in the male urogenital system during
CC late embryogenesis: at day 14.5, expressed in the outbuddings of the
CC pelvic region of the urogenital sinus, and, at lower levels, in the
CC prospective urethra. Expression is confined to the epithelial cells
CC that are invaginating into the surrounding mesenchyme, with highest
CC levels at the leading edge. At 17.5 dpc, present in the developing
CC ventral, dorsolateral and anterior prostatic buds, in the nascent
CC bulbourethral glands, as well as in the epithelial ducts that join the
CC glands to the prospective urethra. During postnatal growth and
CC morphogenesis of the prostate, high expression is maintain at sites of
CC ductal outgrowth and branching. In the developing testis, detected at
CC 14.5 and 17.5 dpc in the medullary cords, which form seminiferous
CC tubules. {ECO:0000269|PubMed:10415359}.
CC -!- INDUCTION: By androgens (PubMed:8943214). During embryonic development,
CC induced and maintained by sonic hedgehog in pre-somitic mesoderm, in
CC immature somites and in urogenital sinus, but not in the other
CC expression domains (PubMed:10906459). {ECO:0000269|PubMed:10906459,
CC ECO:0000269|PubMed:8943214}.
CC -!- PTM: Ubiquitinated by TOPORS; monoubiquitinated at several residues and
CC also polyubiquitinated on single residues.
CC {ECO:0000250|UniProtKB:Q99801}.
CC -!- DISRUPTION PHENOTYPE: Defects in prostate ductal morphogenesis and
CC secretory protein production (PubMed:10215624, PubMed:10906459). The
CC bulbourethral gland displays prostatic epithelial hyperplasia, which
CC increases in severity with age (PubMed:10215624, PubMed:10906459). Mice
CC also display morphogenetic defects of minor salivary glands, which are
CC reduced in size and exhibit severely altered duct morphology
CC (PubMed:10906459). {ECO:0000269|PubMed:10215624,
CC ECO:0000269|PubMed:10906459}.
CC -!- SIMILARITY: Belongs to the NK-3 homeobox family. {ECO:0000305}.
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DR EMBL; U73460; AAC52956.1; -; mRNA.
DR EMBL; U88542; AAB58025.1; -; mRNA.
DR CCDS; CCDS27237.1; -.
DR RefSeq; NP_035051.1; NM_010921.3.
DR AlphaFoldDB; P97436; -.
DR SMR; P97436; -.
DR BioGRID; 201781; 5.
DR STRING; 10090.ENSMUSP00000022646; -.
DR PhosphoSitePlus; P97436; -.
DR PaxDb; P97436; -.
DR PRIDE; P97436; -.
DR ProteomicsDB; 252902; -.
DR Antibodypedia; 9788; 776 antibodies from 40 providers.
DR DNASU; 18095; -.
DR Ensembl; ENSMUST00000022646; ENSMUSP00000022646; ENSMUSG00000022061.
DR GeneID; 18095; -.
DR KEGG; mmu:18095; -.
DR UCSC; uc007umd.1; mouse.
DR CTD; 4824; -.
DR MGI; MGI:97352; Nkx3-1.
DR VEuPathDB; HostDB:ENSMUSG00000022061; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000160930; -.
DR HOGENOM; CLU_049543_2_0_1; -.
DR InParanoid; P97436; -.
DR OMA; LYCLGSW; -.
DR OrthoDB; 1398668at2759; -.
DR PhylomeDB; P97436; -.
DR TreeFam; TF315720; -.
DR BioGRID-ORCS; 18095; 2 hits in 74 CRISPR screens.
DR PRO; PR:P97436; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P97436; protein.
DR Bgee; ENSMUSG00000022061; Expressed in prostate gland ventral lobe and 80 other tissues.
DR ExpressionAtlas; P97436; baseline and differential.
DR Genevisible; P97436; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0090734; C:site of DNA damage; ISO:MGI.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0097162; F:MADS box domain binding; IDA:UniProtKB.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0030521; P:androgen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0035907; P:dorsal aorta development; IEP:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IMP:MGI.
DR GO; GO:0007507; P:heart development; IEP:BHF-UCL.
DR GO; GO:0035260; P:internal genitalia morphogenesis; TAS:BHF-UCL.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0060037; P:pharyngeal system development; IEP:BHF-UCL.
DR GO; GO:2000836; P:positive regulation of androgen secretion; ISS:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0030850; P:prostate gland development; IEP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0033574; P:response to testosterone; IMP:UniProtKB.
DR GO; GO:0007431; P:salivary gland development; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IEP:BHF-UCL.
DR GO; GO:0001655; P:urogenital system development; IEP:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Tumor suppressor;
KW Ubl conjugation.
FT CHAIN 1..237
FT /note="Homeobox protein Nkx-3.1"
FT /id="PRO_0000048946"
FT DNA_BIND 125..184
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 108..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ 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
