P42586 (NKX22_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein Nkx-2.2

Alternative name(s):
Homeobox protein NK-2 homolog B

Gene names

Name:	Nkx2-2
Synonyms:	Nkx-2.2, Nkx2b

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional activator. Required for the maintenance of NEUROD1 expression in the horomone-producing endocrine cells of the pancreas. May be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Associates with chromatin at the NEUROD1 promoter region. Binds to a subset of consensus elements within the NEUROD1 promoter. Ref.5
Subunit structure	Interacts with OLIG2. Ref.4
Subcellular location	Nucleus Ref.4.
Tissue specificity	Expressed in restricted areas of the developing CNS: the hindbrain and forebrain, and pancreas.
Developmental stage	Expressed during embryogenesis.
Domain	The homeodomain is essential for interaction with OLIG2.
Sequence similarities	Belongs to the NK-2 homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	astrocyte differentiation Inferred from mutant phenotype PubMed 19258013. Source: MGI digestive tract development Inferred from mutant phenotype PubMed 18987169. Source: MGI negative regulation of neuron differentiation Inferred from direct assay PubMed 10830170. Source: MGI neuron fate specification Inferred from genetic interaction PubMed 16339193. Source: MGI oligodendrocyte development Inferred from mutant phenotype PubMed 11526078. Source: MGI pancreatic A cell fate commitment Inferred from mutant phenotype PubMed 17202186. Source: MGI pancreatic PP cell fate commitment Inferred from genetic interaction PubMed 17988662. Source: MGI positive regulation of neuron differentiation Inferred from direct assay PubMed 10830170. Source: MGI positive regulation of oligodendrocyte differentiation Inferred from genetic interaction PubMed 11566099. Source: MGI positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.5. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 11526078PubMed 14701942. Source: MGI smoothened signaling pathway Inferred from direct assay PubMed 18590716. Source: MGI spinal cord motor neuron differentiation Inferred from mutant phenotype PubMed 10217145. Source: MGI spinal cord oligodendrocyte cell fate specification Inferred from direct assay PubMed 18287202. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW type B pancreatic cell development Inferred from direct assay PubMed 17456846. Source: MGI type B pancreatic cell fate commitment Inferred from mutant phenotype PubMed 17202186PubMed 17988662. Source: MGI ventral spinal cord interneuron fate determination Inferred from mutant phenotype PubMed 10217145. Source: MGI
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from direct assay Ref.5. Source: UniProtKB core promoter proximal region DNA binding Inferred from direct assay Ref.5. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 14701942. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.4PubMed 14701942. Source: MGI transcription coactivator activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 273	273	Homeobox protein Nkx-2.2		PRO_0000048931
Regions
	DNA binding	128 – 187	60	Homeobox Ref.5
Experimental info
	Mutagenesis	184	1	K → I: Inhibits DNA-binding activity and transcriptional activation of NEUROD1 expression. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P42586 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 1F3DBB8127667F19	FASTA	273	30,126
	10 20 30 40 50 60 MSLTNTKTGF SVKDILDLPD TNDEDGSVAE GPEEESEGPE PAKRAGPLGQ GALDAVQSLP 70 80 90 100 110 120 LKSPFYDSSD NPYTRWLAST EGLQYSLHGL AASAPPQDSS SKSPEPSADE SPDNDKETQG 130 140 150 160 170 180 GGGDAGKKRK RRVLFSKAQT YELERRFRQQ RYLSAPEREH LASLIRLTPT QVKIWFQNHR 190 200 210 220 230 240 YKMKRARAEK GMEVTPLPSP RRVAVPVLVR DGKPCHALKA QDLAAATFQA GIPFSAYSAQ 250 260 270 SLQHMQYNAQ YSSASTPQYP TAHPLVQAQQ WTW

References

[1]	"The embryonic vertebrate forebrain: the prosomeric model." Rubenstein J.L., Martinez S., Shimamura K., Puelles L. Science 266:578-580(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The cDNA sequence of murine Nkx-2.2." Hartigan D.J., Rubenstein J.L. Gene 168:271-272(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain." Price M., Lazzaro D., Pohl T., Mattei M.-G., Ruether U., Olivo J.-C., Duboule D., di Lauro R. Neuron 8:241-255(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-196.
[4]	"Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex." Sun T., Dong H., Wu L., Kane M., Rowitch D.H., Stiles C.D. J. Neurosci. 23:9547-9556(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH OLIG2, SUBCELLULAR LOCATION.
[5]	"Cooperative transcriptional regulation of the essential pancreatic islet gene NeuroD1 (beta2) by Nkx2.2 and neurogenin 3." Anderson K.R., Torres C.A., Solomon K., Becker T.C., Newgard C.B., Wright C.V., Hagman J., Sussel L. J. Biol. Chem. 284:31236-31248(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH CHROMATIN, DNA-BINDING, MUTAGENESIS OF LYS-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U31566 mRNA. Translation: AAA79303.1. S83259 Genomic DNA. No translation available.
IPI	IPI00117502.
PIR	JC4634.
RefSeq	NP_035049.1. NM_010919.2.
UniGene	Mm.330639.
3D structure databases
ProteinModelPortal	P42586.
SMR	P42586. Positions 127-189.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4103861.
Proteomic databases
PaxDb	P42586.
PRIDE	P42586.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000067075; ENSMUSP00000069666; ENSMUSG00000027434.
GeneID	18088.
KEGG	mmu:18088.
UCSC	uc008msu.1. mouse.
Organism-specific databases
CTD	4821.
MGI	MGI:97347. Nkx2-2.
Phylogenomic databases
eggNOG	NOG310976.
HOGENOM	HOG000231923.
HOVERGEN	HBG006689.
InParanoid	P42586.
KO	K08029.
Enzyme and pathway databases
Reactome	REACT_13641. Regulation of Beta-Cell Development.
Gene expression databases
ArrayExpress	P42586.
Bgee	P42586.
Genevestigator	P42586.
GermOnline	ENSMUSG00000027434. Mus musculus.
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
NextBio	293225.
SOURCE	Search...

Entry information

Entry name

NKX22_MOUSE

Accession

Primary (citable) accession number: P42586

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program