Reviewed, UniProtKB/Swiss-Prot Q99801 (NKX31_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	234 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Could play an important role in regulating proliferation of glandular epithelium and in the formation of ducts in prostate.
Subunit structure	Interacts with serum response factor (SRF) By similarity. Interacts with SPDEF. Interacts with WDR77.
Subcellular location	Nucleus.
Tissue specificity	Highly expressed in the prostate and, at a lower level, in the testis.
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.
Involvement in disease	NKX3-1 has been thought to be one of the target gene of the 8p21 loss of heterozygosity, common in prostate cancer, but neither disruption of the coding region of the gene, nor mutations have been found in prostate cancer.
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
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Repressor
Gene Ontology (GO)
Biological process	multicellular organismal development Ref.2 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Ref.3 Non-traceable author statement. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: IntAct sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.3 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TOP1	P11387	3	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.7		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

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). 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). 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). 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). 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: 9226374] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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: 9537602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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: 11137288] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). 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: 15489334] [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: 11809674] [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: 12972618] [Abstract] Cited for: INTERACTION WITH WDR77.
[7]	"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: 9377551] [Abstract] Cited for: VARIANT CYS-52.
[8]	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
EMBLGenBankDDBJ	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_006158.2.
UniGene	Hs.55999
3D structure databases
HSSP	HSSP built from PDB template 1FTT based on UniProtKB P23441.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99801. 2 interactions.
PTM databases
PhosphoSite	Q99801.
Proteomic databases
PRIDE	Q99801.
Genome annotation databases
Ensembl	ENSG00000167034. Homo sapiens. [Contig view]
GeneID	4824.
KEGG	hsa:4824.
Organism-specific databases
GeneCards	GC08M023592.
H-InvDB	HIX0034274.
HGNC	HGNC:7838. NKX3-1.
MIM	602041. gene.
PharmGKB	PA31645.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q99801.
OMA	Q99801. TEPERHL.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity. hnf3apathway. FOXA1 transcription factor network.
Gene expression databases
ArrayExpress	Q99801.
Bgee	Q99801.
CleanEx	HS_NKX3-1.
GermOnline	ENSG00000167034. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)