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Q99801 (NKX31_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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:NKX3.1, NKX3A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length234 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. 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 inhibit proliferation and invasion activities of PC-3 prostate cancer cells. Ref.8

Subunit structure

Interacts with serum response factor (SRF) By similarity. Interacts with SPDEF. Interacts with WDR77. Interacts with TOPORS which polyubiquitinates NKX3-1 and induces its proteasomal degradation. Ref.5 Ref.6 Ref.7

Subcellular location

Nucleus Ref.3.

Tissue specificity

Highly expressed in the prostate and, at a lower level, in the testis. Ref.1 Ref.2

Induction

By androgens and, in the LNCaP cell line, by estrogens. Androgenic control may be lost in prostate cancer cells during tumor progression from an androgen-dependent to an androgen-independent phase. Ref.1 Ref.2 Ref.3

Post-translational modification

Ubiquitinated by TOPORS; monoubiquitinated at several residues and also polyubiquitinated on single residues. Ref.7

Sequence similarities

Belongs to the NK-3 homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseTumor suppressor
   DomainHomeobox
   LigandDNA-binding
   Molecular functionRepressor
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 17486276PubMed 19266349. Source: UniProtKB

androgen receptor signaling pathway

Inferred from direct assay PubMed 19886863. Source: UniProtKB

branching involved in prostate gland morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

branching morphogenesis of an epithelial tube

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to drug

Inferred from expression pattern PubMed 18757402. Source: UniProtKB

cellular response to hypoxia

Inferred from direct assay PubMed 21056661. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern PubMed 18757402. Source: UniProtKB

cellular response to steroid hormone stimulus

Inferred from direct assay PubMed 19886863. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 18757402. Source: UniProtKB

dorsal aorta development

Inferred from electronic annotation. Source: Ensembl

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

heart development

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from electronic annotation. Source: Ensembl

metanephros development

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle arrest

Inferred from direct assay PubMed 19266349. Source: UniProtKB

multicellular organismal development

Traceable author statement Ref.2. Source: ProtInc

negative regulation of cell proliferation

Inferred from direct assay PubMed 17486276PubMed 19266349. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of epithelial cell proliferation involved in prostate gland development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of estrogen receptor binding

Inferred from direct assay PubMed 18794125. Source: UniProtKB

negative regulation of gene expression

Inferred from direct assay PubMed 17486276. Source: UniProtKB

negative regulation of insulin-like growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of mitotic cell cycle

Inferred from direct assay PubMed 19266349. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18794125PubMed 19597465. Source: UniProtKB

pharyngeal system development

Inferred from electronic annotation. Source: Ensembl

positive regulation of androgen secretion

Inferred from direct assay PubMed 19886863. Source: UniProtKB

positive regulation of apoptotic signaling pathway

Inferred from direct assay PubMed 20599703. Source: UniProtKB

positive regulation of cell death

Inferred from direct assay PubMed 19266349. Source: UniProtKB

positive regulation of cell division

Inferred from mutant phenotype PubMed 20855495. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 18360715. Source: UniProtKB

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

Inferred from direct assay PubMed 20599703. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 17486276PubMed 20599703. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 17486276. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from mutant phenotype PubMed 20855495. Source: BHF-UCL

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from direct assay PubMed 20395202. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from direct assay PubMed 20395202. Source: GOC

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 20395202. Source: UniProtKB

positive regulation of response to DNA damage stimulus

Inferred from direct assay PubMed 20395202. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19797053. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 18360715. Source: UniProtKB

protein kinase B signaling

Inferred from mutant phenotype PubMed 19597465. Source: UniProtKB

regulation of transcription, DNA-templated

Non-traceable author statement Ref.3. Source: UniProtKB

response to testosterone

Inferred from sequence or structural similarity. Source: UniProtKB

salivary gland development

Inferred from sequence or structural similarity. Source: UniProtKB

somitogenesis

Inferred from electronic annotation. Source: Ensembl

steroid hormone mediated signaling pathway

Inferred from direct assay PubMed 18794125. Source: GOC

   Cellular_componentintracellular

Inferred from direct assay PubMed 19597465. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 18757402PubMed 19263243. Source: UniProtKB

   Molecular_functionRNA polymerase II core promoter sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

androgen receptor activity

Inferred from direct assay PubMed 19886863. Source: UniProtKB

core promoter binding

Inferred from direct assay PubMed 18974119. Source: UniProtKB

estrogen receptor activity

Inferred from direct assay PubMed 18794125. Source: UniProtKB

estrogen receptor binding

Inferred from direct assay PubMed 18794125. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction PubMed 18974119. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7PubMed 18296735PubMed 19797053. Source: UniProtKB

protein kinase activator activity

Inferred from direct assay PubMed 20395202. Source: UniProtKB

protein self-association

Inferred from direct assay PubMed 19780584. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 19780584. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Non-traceable author statement Ref.3. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 20716579. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19263243. Source: UniProtKB

transcription regulatory region sequence-specific DNA binding

Inferred from direct assay PubMed 20855495. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TOP1P113876EBI-1385894,EBI-876302

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q99801-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99801-2)

Also known as: V2;

The sequence of this isoform differs from the canonical sequence as follows:
     8-56: Missing.
Isoform 3 (identifier: Q99801-3)

Also known as: V4;

The sequence of this isoform differs from the canonical sequence as follows:
     13-87: Missing.
Isoform 4 (identifier: Q99801-4)

Also known as: V3;

The sequence of this isoform differs from the canonical sequence as follows:
     15-83: Missing.
Isoform 5 (identifier: Q99801-5)

Also known as: V1;

The sequence of this isoform differs from the canonical sequence as follows:
     40-83: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 234234Homeobox protein Nkx-3.1
PRO_0000048945

Regions

DNA binding124 – 18360Homeobox

Natural variations

Alternative sequence8 – 5649Missing in isoform 2.
VSP_002230
Alternative sequence13 – 8775Missing in isoform 3.
VSP_002231
Alternative sequence15 – 8369Missing in isoform 4.
VSP_002232
Alternative sequence40 – 8344Missing in isoform 5.
VSP_002233
Natural variant521R → C. Ref.10
Corresponds to variant rs2228013 [ dbSNP | Ensembl ].
VAR_011612

Experimental info

Sequence conflict81R → W in AAG39737. Ref.3
Sequence conflict851E → D in AAB38747. Ref.2
Sequence conflict1351Q → R in AAG39738. Ref.3
Sequence conflict1961S → F in AAB38747. Ref.2
Sequence conflict2241Y → H in AAB38747. Ref.2
Sequence conflict2341W → G in AAB68662. Ref.1

Secondary structure

......... 234
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 26, 2001. Version 2.
Checksum: C99A0943E15B2A55

FASTA23426,350
        10         20         30         40         50         60 
MLRVPEPRPG EAKAEGAAPP TPSKPLTSFL IQDILRDGAQ RQGGRTSSQR QRDPEPEPEP 

        70         80         90        100        110        120 
EPEGGRSRAG AQNDQLSTGP RAAPEEAETL AETEPERHLG SYLLDSENTS GALPRLPQTP 

       130        140        150        160        170        180 
KQPQKRSRAA FSHTQVIELE RKFSHQKYLS APERAHLAKN LKLTETQVKI WFQNRRYKTK 

       190        200        210        220        230 
RKQLSSELGD LEKHSSLPAL KEEAFSRASL VSVYNSYPYY PYLYCVGSWS PAFW 

« Hide

Isoform 2 (V2) [UniParc].

Checksum: 5A3A3233AA1C05EB
Show »

FASTA18521,099
Isoform 3 (V4) [UniParc].

Checksum: AEE13D060B421ED8
Show »

FASTA15918,423
Isoform 4 (V3) [UniParc].

Checksum: 2B8B0D19FBD83A8D
Show »

FASTA16519,049
Isoform 5 (V1) [UniParc].

Checksum: 985A34212DCEDA27
Show »

FASTA19021,626

References

« Hide 'large scale' references
[1]"A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer."
He W.-W., Sciavolino P.J., Wing J., Augustus M., Hudson P., Meissner P.S., Curtis R.T., Shell B.K., Bostwick D.G., Tindall D.J., Gelmann E.P., Abate-Shen C., Carter K.C.
Genomics 43:69-77(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION BY ANDROGENS.
Tissue: Prostate.
[2]"Isolation and androgen regulation of the human homeobox cDNA, NKX3.1."
Prescott J.L., Blok L., Tindall D.J.
Prostate 35:71-80(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION BY ANDROGENS.
[3]"Full-length cDNA sequence and genomic organization of human NKX3A --alternative mRNA forms and regulation by both androgens and estrogens."
Korkmaz K.S., Korkmaz C.G., Ragnhildstveit E., Kizildag S., Pretlow T.G., Saatcioglu F.
Gene 260:25-36(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), SUBCELLULAR LOCATION, INDUCTION BY ESTROGENS.
Tissue: Prostate.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[5]"NKX-3.1 interacts with prostate-derived Ets factor and regulates the activity of the PSA promoter."
Chen H., Nandi A.K., Li X., Bieberich C.J.
Cancer Res. 62:338-340(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPDEF.
[6]"Purification and identification of a novel complex which is involved in androgen receptor-dependent transcription."
Hosohata K., Li P., Hosohata Y., Qin J., Roeder R.G., Wang Z.
Mol. Cell. Biol. 23:7019-7029(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WDR77.
[7]"Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1."
Guan B., Pungaliya P., Li X., Uquillas C., Mutton L.N., Rubin E.H., Bieberich C.J.
J. Biol. Chem. 283:4834-4840(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TOPORS, UBIQUITINATION BY TOPORS.
[8]"Gene expression profiles in the PC-3 human prostate cancer cells induced by NKX3.1."
Zhang P., Liu W., Zhang J., Guan H., Chen W., Cui X., Liu Q., Jiang A.
Mol. Biol. Rep. 37:1505-1512(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TUMOR SUPPRESSOR.
[9]"Solution NMR structure of homeobox domain of homeobox protein NKX-3.1 from Homo sapiens, Northeast structural genomics consortium target HR6470A."
Northeast structural genomics consortium (NESG)
Submitted (APR-2011) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 132-189.
[10]"Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers."
Voeller H.J., Augustus M., Madike V., Bova G.S., Carter K.C., Gelmann E.P.
Cancer Res. 57:4455-4459(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-52.
[11]Erratum
Voeller H.J., Augustus M., Madike V., Bova G.S., Carter K.C., Gelmann E.P.
Cancer Res. 57:5613-5613(1997)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U91540 mRNA. Translation: AAB68662.1.
U80669 mRNA. Translation: AAB38747.1.
AF247704 mRNA. Translation: AAG09781.1.
AF249669 mRNA. Translation: AAG39735.1.
AF249670 mRNA. Translation: AAG39736.1.
AF249671 mRNA. Translation: AAG39737.1.
AF249672 mRNA. Translation: AAG39738.1.
BC074863 mRNA. Translation: AAH74863.1.
BC074864 mRNA. Translation: AAH74864.1.
CCDSCCDS59095.1. [Q99801-3]
CCDS6042.1. [Q99801-1]
RefSeqNP_001243268.1. NM_001256339.1. [Q99801-3]
NP_006158.2. NM_006167.3. [Q99801-1]
UniGeneHs.55999.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L9RNMR-A132-189[»]
DisProtDP00683.
ProteinModelPortalQ99801.
SMRQ99801. Positions 134-189.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110888. 34 interactions.
IntActQ99801. 1 interaction.
STRING9606.ENSP00000370253.

PTM databases

PhosphoSiteQ99801.

Polymorphism databases

DMDM17377578.

Proteomic databases

MaxQBQ99801.
PaxDbQ99801.
PRIDEQ99801.

Protocols and materials databases

DNASU4824.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380871; ENSP00000370253; ENSG00000167034. [Q99801-1]
ENST00000523261; ENSP00000429729; ENSG00000167034. [Q99801-3]
GeneID4824.
KEGGhsa:4824.
UCSCuc011kzx.2. human. [Q99801-1]
uc031tao.1. human. [Q99801-3]

Organism-specific databases

CTD4824.
GeneCardsGC08M023536.
HGNCHGNC:7838. NKX3-1.
HPAHPA025693.
MIM602041. gene.
neXtProtNX_Q99801.
PharmGKBPA31645.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238786.
HOGENOMHOG000231923.
HOVERGENHBG006689.
InParanoidQ99801.
KOK09348.
OMAGAQRQGG.
OrthoDBEOG7QZG9Z.
PhylomeDBQ99801.
TreeFamTF315720.

Enzyme and pathway databases

SignaLinkQ99801.

Gene expression databases

BgeeQ99801.
CleanExHS_NKX3-1.
GenevestigatorQ99801.

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

ChiTaRSNKX3-1. human.
GeneWikiNKX3-1.
GenomeRNAi4824.
NextBio18580.
PROQ99801.
SOURCESearch...

Entry information

Entry nameNKX31_HUMAN
AccessionPrimary (citable) accession number: Q99801
Secondary accession number(s): O15465 expand/collapse secondary AC list , Q9H2P4, Q9H2P5, Q9H2P6, Q9H2P7, Q9HBG0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 26, 2001
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM