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P97436 (NKX31_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein Nkx-3.1
Alternative name(s):
Homeobox protein NK-3 homolog A
Gene names
Name:Nkx3-1
Synonyms:Nkx-3.1, Nkx3a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length237 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3

Subunit structure

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.

Subcellular location

Nucleus By similarity.

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.

Post-translational modification

Ubiquitinated by TOPORS; monoubiquitinated at several residues and also polyubiquitinated on single residues By similarity.

Sequence similarities

Belongs to the NK-3 homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DiseaseTumor suppressor
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

androgen receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

branching involved in prostate gland morphogenesis

Inferred from mutant phenotype PubMed 10215624PubMed 10906459PubMed 11002344. Source: MGI

branching morphogenesis of an epithelial tube

Inferred from mutant phenotype PubMed 11002344. Source: MGI

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

cellular response to steroid hormone stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

dorsal aorta development

Inferred from expression pattern Ref.2. Source: UniProtKB

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from mutant phenotype PubMed 10906459. Source: MGI

heart development

Inferred from expression pattern PubMed 9621431. Source: BHF-UCL

internal genitalia morphogenesis

Traceable author statement PubMed 9621431. Source: BHF-UCL

male gonad development

Inferred from expression pattern Ref.2. Source: UniProtKB

metanephros development

Inferred from expression pattern Ref.2. Source: UniProtKB

mitotic cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from genetic interaction PubMed 19258508. Source: MGI

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 11002344. Source: MGI

negative regulation of epithelial cell proliferation involved in prostate gland development

Inferred from mutant phenotype PubMed 11002344PubMed 11839815. Source: MGI

negative regulation of estrogen receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin-like growth factor receptor signaling pathway

Inferred from direct assay PubMed 19258508. Source: MGI

negative regulation of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 19597465. Source: UniProtKB

pharyngeal system development

Inferred from expression pattern PubMed 9621431. Source: BHF-UCL

positive regulation of androgen secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell death

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell division

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10993896. Source: MGI

prostate gland development

Inferred from expression pattern Ref.2. Source: UniProtKB

protein kinase B signaling

Inferred from mutant phenotype PubMed 19597465. Source: UniProtKB

response to testosterone

Inferred from mutant phenotype Ref.2. Source: UniProtKB

salivary gland development

Inferred from mutant phenotype PubMed 10906459. Source: MGI

somitogenesis

Inferred from expression pattern PubMed 9621431. Source: BHF-UCL

steroid hormone mediated signaling pathway

Inferred from sequence or structural similarity. Source: GOC

transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18296735. Source: GOC

urogenital system development

Inferred from expression pattern Ref.2. Source: UniProtKB

   Cellular_componentintracellular

Inferred from direct assay PubMed 19597465. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15987773. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 10993896. Source: MGI

MADS box domain binding

Inferred from direct assay PubMed 18296735. Source: UniProtKB

androgen receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

core promoter binding

Inferred from sequence or structural similarity. Source: UniProtKB

cysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

estrogen receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

estrogen receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 18816836. Source: MGI

protein kinase activator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein self-association

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.2. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 10993896. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 18296735. Source: UniProtKB

transcription regulatory region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 237237Homeobox protein Nkx-3.1
PRO_0000048946

Regions

DNA binding125 – 18460Homeobox

Sequences

Sequence LengthMass (Da)Tools
P97436 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 4B074387F3BA1223

FASTA23726,824
        10         20         30         40         50         60 
MLRVAEPREP RVEAGGRSPW AAPPTQSKRL TSFLIQDILR DRAERHGGHS GNPQHSPDPR 

        70         80         90        100        110        120 
RDSAPEPDKA GGRGVAPEDP PSIRHSPAET PTEPESDAHF ETYLLDCEHN PGDLASAPQV 

       130        140        150        160        170        180 
TKQPQKRSRA AFSHTQVIEL ERKFSHQKYL SAPERAHLAK NLKLTETQVK IWFQNRRYKT 

       190        200        210        220        230 
KRKQLSEDLG VLEKNSPLSL PALKDDSLPS TSLVSVYTSY PYYPYLYCLG SWHPSFW 

« Hide

References

[1]"Prostate-specific and androgen-dependent expression of a novel homeobox gene."
Bieberich C.J., Fujita K., He W.-W., Jay G.
J. Biol. Chem. 271:31779-31782(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Prostate.
[2]"Tissue-specific expression of murine Nkx3.1 in the male urogenital system."
Sciavolino P.J., Abrams E.W., Yang L., Austenberg L.P., Shen M.M., Abate-Shen C.
Dev. Dyn. 209:127-138(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Swiss Webster.
Tissue: Embryo.
[3]"Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis."
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.
Cancer Res. 62:2999-3004(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TUMOR SUPPRESSOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U73460 mRNA. Translation: AAC52956.1.
U88542 mRNA. Translation: AAB58025.1.
CCDSCCDS27237.1.
RefSeqNP_035051.1. NM_010921.3.
UniGeneMm.3520.

3D structure databases

ProteinModelPortalP97436.
SMRP97436. Positions 135-190.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201781. 2 interactions.
STRING10090.ENSMUSP00000022646.

PTM databases

PhosphoSiteP97436.

Proteomic databases

PRIDEP97436.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022646; ENSMUSP00000022646; ENSMUSG00000022061.
GeneID18095.
KEGGmmu:18095.
UCSCuc007umd.1. mouse.

Organism-specific databases

CTD4824.
MGIMGI:97352. Nkx3-1.

Phylogenomic databases

eggNOGNOG238786.
HOGENOMHOG000231923.
HOVERGENHBG006689.
InParanoidP97436.
KOK09348.
OMAGAQRQGG.
OrthoDBEOG7QZG9Z.
PhylomeDBP97436.
TreeFamTF315720.

Gene expression databases

ArrayExpressP97436.
BgeeP97436.
CleanExMM_NKX3-1.
GenevestigatorP97436.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00024. HOMEOBOX.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio293247.
PROP97436.
SOURCESearch...

Entry information

Entry nameNKX31_MOUSE
AccessionPrimary (citable) accession number: P97436
Secondary accession number(s): O09087
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot