Q99801 (NKX31_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein Nkx-3.1

Alternative name(s):
Homeobox protein NK-3 homolog A

Gene names

Name:	NKX3-1
Synonyms:	NKX3.1, NKX3A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	234 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Repressor
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 17486276PubMed 19266349. 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 tumor necrosis factor Inferred from expression pattern PubMed 18757402. Source: UniProtKB dorsal aorta development Inferred from electronic annotation. Source: Compara epithelial cell proliferation involved in salivary gland morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB heart development Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara metanephros development Inferred from electronic annotation. Source: Compara mitotic cell cycle arrest Inferred from direct assay PubMed 19266349. 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 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-dependent Inferred from direct assay PubMed 18794125PubMed 19597465. Source: UniProtKB pharyngeal system development Inferred from electronic annotation. Source: Compara positive regulation of androgen secretion Inferred from direct assay PubMed 19886863. 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 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 cascade 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 protein kinase B signaling cascade Inferred from mutant phenotype PubMed 19597465. Source: UniProtKB response to testosterone stimulus Inferred from sequence or structural similarity. Source: UniProtKB somitogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay PubMed 18757402PubMed 19263243. Source: UniProtKB
Molecular_function	RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara 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 protein binding transcription factor activity Inferred from direct assay PubMed 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 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
TOP1	P11387	6	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 234

234

Homeobox protein Nkx-3.1

PRO_0000048945

Regions

DNA binding

124 – 183

60

Homeobox

Natural variations

Alternative sequence

8 – 56

49

Missing in isoform 2.

VSP_002230

Alternative sequence

13 – 87

75

Missing in isoform 3.

VSP_002231

Alternative sequence

15 – 83

69

Missing in isoform 4.

VSP_002232

Alternative sequence

40 – 83

44

Missing in isoform 5.

VSP_002233

Natural variant

52

1

R → C. Ref.10
Corresponds to variant rs2228013 [ dbSNP | Ensembl ].

VAR_011612

Experimental info

Sequence conflict

8

1

R → W in AAG39737. Ref.3

Sequence conflict

85

1

E → D in AAB38747. Ref.2

Sequence conflict

135

1

Q → R in AAG39738. Ref.3

Sequence conflict

196

1

S → F in AAB38747. Ref.2

Sequence conflict

224

1

Y → H in AAB38747. Ref.2

Sequence conflict

234

1

W → G in AAB68662. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

234

Helix Strand Turn

Details...

Helix

133 – 145

13

Helix

151 – 160

10

Helix

165 – 178

14

Beta strand

182 – 185

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 26, 2001. Version 2. Checksum: C99A0943E15B2A55	FASTA	234	26,350
	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
	Isoform 2 (V2) [UniParc]. Checksum: 5A3A3233AA1C05EB	FASTA	185	21,099
	10 20 30 40 50 60 MLRVPEPEPE PEPEGGRSRA GAQNDQLSTG PRAAPEEAET LAETEPERHL GSYLLDSENT 70 80 90 100 110 120 SGALPRLPQT PKQPQKRSRA AFSHTQVIEL ERKFSHQKYL SAPERAHLAK NLKLTETQVK 130 140 150 160 170 180 IWFQNRRYKT KRKQLSSELG DLEKHSSLPA LKEEAFSRAS LVSVYNSYPY YPYLYCVGSW SPAFW
	Isoform 3 (V4) [UniParc]. Checksum: AEE13D060B421ED8	FASTA	159	18,423
	10 20 30 40 50 60 MLRVPEPRPG EAETLAETEP ERHLGSYLLD SENTSGALPR LPQTPKQPQK RSRAAFSHTQ 70 80 90 100 110 120 VIELERKFSH QKYLSAPERA HLAKNLKLTE TQVKIWFQNR RYKTKRKQLS SELGDLEKHS 130 140 150 SLPALKEEAF SRASLVSVYN SYPYYPYLYC VGSWSPAFW
	Isoform 4 (V3) [UniParc]. Checksum: 2B8B0D19FBD83A8D	FASTA	165	19,049
	10 20 30 40 50 60 MLRVPEPRPG EAKAPEEAET LAETEPERHL GSYLLDSENT SGALPRLPQT PKQPQKRSRA 70 80 90 100 110 120 AFSHTQVIEL ERKFSHQKYL SAPERAHLAK NLKLTETQVK IWFQNRRYKT KRKQLSSELG 130 140 150 160 DLEKHSSLPA LKEEAFSRAS LVSVYNSYPY YPYLYCVGSW SPAFW
	Isoform 5 (V1) [UniParc]. Checksum: 985A34212DCEDA27	FASTA	190	21,626
	10 20 30 40 50 60 MLRVPEPRPG EAKAEGAAPP TPSKPLTSFL IQDILRDGAP EEAETLAETE PERHLGSYLL 70 80 90 100 110 120 DSENTSGALP RLPQTPKQPQ KRSRAAFSHT QVIELERKFS HQKYLSAPER AHLAKNLKLT 130 140 150 160 170 180 ETQVKIWFQN RRYKTKRKQL SSELGDLEKH SSLPALKEEA FSRASLVSVY NSYPYYPYLY 190 CVGSWSPAFW

References

	« Hide 'large scale' referencesShow '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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00018412.
IPI00215781.
IPI00215782.
IPI00215783.
IPI00848258.

RefSeq

NP_001243268.1. NM_001256339.1.
NP_006158.2. NM_006167.3.

UniGene

Hs.55999.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L9R	NMR	-	A	132-189	[»]

ProteinModelPortal

Q99801.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99801. 1 interaction.

STRING

9606.ENSP00000370253.

PTM databases

PhosphoSite

Q99801.

Polymorphism databases

DMDM

17377578.

Proteomic databases

PaxDb

Q99801.

PRIDE

Q99801.

Protocols and materials databases

DNASU

4824.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380871; ENSP00000370253; ENSG00000167034.
ENST00000523261; ENSP00000429729; ENSG00000167034.

GeneID

4824.

KEGG

hsa:4824.

UCSC

uc011kzx.2. human.

Organism-specific databases

CTD

4824.

GeneCards

GC08M023536.

HGNC

HGNC:7838. NKX3-1.

HPA

HPA025693.

MIM

602041. gene.

neXtProt

NX_Q99801.

PharmGKB

PA31645.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG238786.

HOGENOM

HOG000231923.

HOVERGEN

HBG006689.

InParanoid

Q99801.

KO

K09348.

OMA

TEPERHL.

OrthoDB

EOG46Q6TS.

PhylomeDB

Q99801.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
hnf3apathway. FOXA1 transcription factor network.

SignaLink

Q99801.

Gene expression databases

Bgee

Q99801.

CleanEx

HS_NKX3-1.

Genevestigator

Q99801.

GermOnline

ENSG00000167034. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR017970. Homeobox_CS.
IPR020479. Homeobox_metazoa.
IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
[Graphical view]

Pfam

PF00046. Homeobox. 1 hit.
[Graphical view]

PRINTS

PR00024. HOMEOBOX.

SMART

SM00389. HOX. 1 hit.
[Graphical view]

SUPFAM

SSF46689. Homeodomain_like. 1 hit.

PROSITE

PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NKX3-1. human.

GenomeRNAi

4824.

NextBio

18580.

SOURCE

Search...

Entry information

Entry name

NKX31_HUMAN

Accession

Primary (citable) accession number: Q99801
Secondary accession number(s): O15465 , Q9H2P4, Q9H2P5, Q9H2P6, Q9H2P7, Q9HBG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 26, 2001
Last modified:	May 29, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.