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Protein

Homeobox protein Nkx-3.1

Gene

Nkx3-1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi125 – 18460HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. androgen receptor activity Source: UniProtKB
  2. core promoter binding Source: UniProtKB
  3. cysteine-type endopeptidase activator activity involved in apoptotic process Source: Ensembl
  4. DNA binding Source: MGI
  5. estrogen receptor activity Source: UniProtKB
  6. estrogen receptor binding Source: UniProtKB
  7. histone deacetylase binding Source: MGI
  8. MADS box domain binding Source: UniProtKB
  9. protein kinase activator activity Source: UniProtKB
  10. protein self-association Source: UniProtKB
  11. sequence-specific DNA binding Source: UniProtKB
  12. sequence-specific DNA binding transcription factor activity Source: MGI
  13. transcription factor binding Source: UniProtKB
  14. transcription regulatory region DNA binding Source: MGI
  15. transcription regulatory region sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. androgen receptor signaling pathway Source: UniProtKB
  3. branching involved in prostate gland morphogenesis Source: MGI
  4. branching morphogenesis of an epithelial tube Source: MGI
  5. cellular response to drug Source: Ensembl
  6. cellular response to hypoxia Source: MGI
  7. cellular response to interleukin-1 Source: Ensembl
  8. cellular response to steroid hormone stimulus Source: UniProtKB
  9. cellular response to tumor necrosis factor Source: Ensembl
  10. dorsal aorta development Source: UniProtKB
  11. epithelial cell proliferation involved in salivary gland morphogenesis Source: MGI
  12. heart development Source: BHF-UCL
  13. internal genitalia morphogenesis Source: BHF-UCL
  14. male gonad development Source: UniProtKB
  15. metanephros development Source: UniProtKB
  16. mitotic cell cycle arrest Source: MGI
  17. negative regulation of cell proliferation Source: MGI
  18. negative regulation of epithelial cell proliferation Source: MGI
  19. negative regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  20. negative regulation of estrogen receptor binding Source: UniProtKB
  21. negative regulation of gene expression Source: MGI
  22. negative regulation of insulin-like growth factor receptor signaling pathway Source: MGI
  23. negative regulation of mitotic cell cycle Source: MGI
  24. negative regulation of transcription, DNA-templated Source: UniProtKB
  25. pharyngeal system development Source: BHF-UCL
  26. positive regulation of androgen secretion Source: UniProtKB
  27. positive regulation of apoptotic signaling pathway Source: MGI
  28. positive regulation of cell death Source: UniProtKB
  29. positive regulation of cell division Source: UniProtKB
  30. positive regulation of cell proliferation Source: UniProtKB
  31. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  32. positive regulation of gene expression Source: UniProtKB
  33. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  34. positive regulation of mitotic cell cycle Source: UniProtKB
  35. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  36. positive regulation of protein kinase activity Source: MGI
  37. positive regulation of protein phosphorylation Source: UniProtKB
  38. positive regulation of response to DNA damage stimulus Source: UniProtKB
  39. positive regulation of transcription, DNA-templated Source: MGI
  40. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  41. prostate gland development Source: UniProtKB
  42. protein kinase B signaling Source: UniProtKB
  43. response to testosterone Source: UniProtKB
  44. salivary gland development Source: MGI
  45. somitogenesis Source: BHF-UCL
  46. steroid hormone mediated signaling pathway Source: MGI
  47. transcription from RNA polymerase II promoter Source: GOC
  48. urogenital system development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-3.1
Alternative name(s):
Homeobox protein NK-3 homolog A
Gene namesi
Name:Nkx3-1
Synonyms:Nkx-3.1, Nkx3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 14

Organism-specific databases

MGIiMGI:97352. Nkx3-1.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. intracellular Source: UniProtKB
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 237237Homeobox protein Nkx-3.1PRO_0000048946Add
BLAST

Post-translational modificationi

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

Keywords - PTMi

Ubl conjugation

Proteomic databases

PRIDEiP97436.

PTM databases

PhosphoSiteiP97436.

Expressioni

Tissue specificityi

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 stagei

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.

Inductioni

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.

Gene expression databases

BgeeiP97436.
CleanExiMM_NKX3-1.
ExpressionAtlasiP97436. baseline and differential.
GenevestigatoriP97436.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi201781. 2 interactions.
STRINGi10090.ENSMUSP00000022646.

Structurei

3D structure databases

ProteinModelPortaliP97436.
SMRiP97436. Positions 135-190.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NK-3 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG238786.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP97436.
KOiK09348.
OMAiGAQRQGG.
OrthoDBiEOG7QZG9Z.
PhylomeDBiP97436.
TreeFamiTF315720.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P97436-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLRVAEPREP RVEAGGRSPW AAPPTQSKRL TSFLIQDILR DRAERHGGHS
60 70 80 90 100
GNPQHSPDPR RDSAPEPDKA GGRGVAPEDP PSIRHSPAET PTEPESDAHF
110 120 130 140 150
ETYLLDCEHN PGDLASAPQV TKQPQKRSRA AFSHTQVIEL ERKFSHQKYL
160 170 180 190 200
SAPERAHLAK NLKLTETQVK IWFQNRRYKT KRKQLSEDLG VLEKNSPLSL
210 220 230
PALKDDSLPS TSLVSVYTSY PYYPYLYCLG SWHPSFW
Length:237
Mass (Da):26,824
Last modified:May 1, 1997 - v1
Checksum:i4B074387F3BA1223
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73460 mRNA. Translation: AAC52956.1.
U88542 mRNA. Translation: AAB58025.1.
CCDSiCCDS27237.1.
RefSeqiNP_035051.1. NM_010921.3.
UniGeneiMm.3520.

Genome annotation databases

EnsembliENSMUST00000022646; ENSMUSP00000022646; ENSMUSG00000022061.
GeneIDi18095.
KEGGimmu:18095.
UCSCiuc007umd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73460 mRNA. Translation: AAC52956.1.
U88542 mRNA. Translation: AAB58025.1.
CCDSiCCDS27237.1.
RefSeqiNP_035051.1. NM_010921.3.
UniGeneiMm.3520.

3D structure databases

ProteinModelPortaliP97436.
SMRiP97436. Positions 135-190.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201781. 2 interactions.
STRINGi10090.ENSMUSP00000022646.

PTM databases

PhosphoSiteiP97436.

Proteomic databases

PRIDEiP97436.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022646; ENSMUSP00000022646; ENSMUSG00000022061.
GeneIDi18095.
KEGGimmu:18095.
UCSCiuc007umd.1. mouse.

Organism-specific databases

CTDi4824.
MGIiMGI:97352. Nkx3-1.

Phylogenomic databases

eggNOGiNOG238786.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP97436.
KOiK09348.
OMAiGAQRQGG.
OrthoDBiEOG7QZG9Z.
PhylomeDBiP97436.
TreeFamiTF315720.

Miscellaneous databases

NextBioi293247.
PROiP97436.
SOURCEiSearch...

Gene expression databases

BgeeiP97436.
CleanExiMM_NKX3-1.
ExpressionAtlasiP97436. baseline and differential.
GenevestigatoriP97436.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiNKX31_MOUSE
AccessioniPrimary (citable) accession number: P97436
Secondary accession number(s): O09087
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: February 4, 2015
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.