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Protein

Homeobox protein Nkx-2.2

Gene

Nkx2-2

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

Functioni

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi128 – 18760HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: UniProtKB
  2. core promoter proximal region DNA binding Source: UniProtKB
  3. sequence-specific DNA binding Source: MGI
  4. sequence-specific DNA binding transcription factor activity Source: MGI
  5. transcription coactivator activity Source: UniProtKB
  6. transcription factor binding Source: MGI

GO - Biological processi

  1. astrocyte differentiation Source: MGI
  2. cell development Source: MGI
  3. cell differentiation Source: MGI
  4. digestive tract development Source: MGI
  5. endocrine pancreas development Source: MGI
  6. negative regulation of neuron differentiation Source: MGI
  7. nervous system development Source: MGI
  8. neuron fate specification Source: MGI
  9. oligodendrocyte development Source: MGI
  10. optic nerve development Source: Ensembl
  11. pancreatic A cell fate commitment Source: MGI
  12. pancreatic PP cell fate commitment Source: MGI
  13. positive regulation of cell differentiation Source: MGI
  14. positive regulation of gene expression Source: MGI
  15. positive regulation of neuron differentiation Source: MGI
  16. positive regulation of oligodendrocyte differentiation Source: MGI
  17. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  18. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  19. regulation of cell differentiation Source: MGI
  20. regulation of transcription, DNA-templated Source: MGI
  21. response to glucose Source: Ensembl
  22. response to progesterone Source: Ensembl
  23. smoothened signaling pathway Source: MGI
  24. spinal cord motor neuron differentiation Source: MGI
  25. spinal cord oligodendrocyte cell differentiation Source: MGI
  26. spinal cord oligodendrocyte cell fate specification Source: MGI
  27. transcription, DNA-templated Source: UniProtKB-KW
  28. type B pancreatic cell development Source: MGI
  29. type B pancreatic cell fate commitment Source: MGI
  30. ventral spinal cord interneuron fate determination Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_214529. Regulation of gene expression in beta cells.
REACT_221082. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-2.2
Alternative name(s):
Homeobox protein NK-2 homolog B
Gene namesi
Name:Nkx2-2
Synonyms:Nkx-2.2, Nkx2b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:97347. Nkx2-2.

Subcellular locationi

Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. intracellular Source: MGI
  2. nucleoplasm Source: Reactome
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi184 – 1841K → I: Inhibits DNA-binding activity and transcriptional activation of NEUROD1 expression. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 273273Homeobox protein Nkx-2.2PRO_0000048931Add
BLAST

Proteomic databases

PaxDbiP42586.
PRIDEiP42586.

Expressioni

Tissue specificityi

Expressed in restricted areas of the developing CNS: the hindbrain and forebrain, and pancreas.

Developmental stagei

Expressed during embryogenesis.

Gene expression databases

BgeeiP42586.
ExpressionAtlasiP42586. baseline and differential.
GenevestigatoriP42586.

Interactioni

Subunit structurei

Interacts with OLIG2.1 Publication

Protein-protein interaction databases

BioGridi201776. 4 interactions.
IntActiP42586. 1 interaction.
MINTiMINT-4103861.

Structurei

3D structure databases

ProteinModelPortaliP42586.
SMRiP42586. Positions 127-189.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The homeodomain is essential for interaction with OLIG2.

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG310976.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP42586.
KOiK08029.
PhylomeDBiP42586.
TreeFamiTF351204.

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.

P42586-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLTNTKTGF SVKDILDLPD TNDEDGSVAE GPEEESEGPE PAKRAGPLGQ
60 70 80 90 100
GALDAVQSLP LKSPFYDSSD NPYTRWLAST EGLQYSLHGL AASAPPQDSS
110 120 130 140 150
SKSPEPSADE SPDNDKETQG GGGDAGKKRK RRVLFSKAQT YELERRFRQQ
160 170 180 190 200
RYLSAPEREH LASLIRLTPT QVKIWFQNHR YKMKRARAEK GMEVTPLPSP
210 220 230 240 250
RRVAVPVLVR DGKPCHALKA QDLAAATFQA GIPFSAYSAQ SLQHMQYNAQ
260 270
YSSASTPQYP TAHPLVQAQQ WTW
Length:273
Mass (Da):30,126
Last modified:October 1, 1996 - v2
Checksum:i1F3DBB8127667F19
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U31566 mRNA. Translation: AAA79303.1.
S83259 Genomic DNA. No translation available.
CCDSiCCDS16834.1.
PIRiJC4634.
RefSeqiNP_035049.1. NM_010919.2.
XP_006498961.1. XM_006498898.1.
XP_006498962.1. XM_006498899.1.
XP_006498963.1. XM_006498900.1.
UniGeneiMm.330639.

Genome annotation databases

EnsembliENSMUST00000067075; ENSMUSP00000069666; ENSMUSG00000027434.
GeneIDi18088.
KEGGimmu:18088.
UCSCiuc008msu.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U31566 mRNA. Translation: AAA79303.1.
S83259 Genomic DNA. No translation available.
CCDSiCCDS16834.1.
PIRiJC4634.
RefSeqiNP_035049.1. NM_010919.2.
XP_006498961.1. XM_006498898.1.
XP_006498962.1. XM_006498899.1.
XP_006498963.1. XM_006498900.1.
UniGeneiMm.330639.

3D structure databases

ProteinModelPortaliP42586.
SMRiP42586. Positions 127-189.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201776. 4 interactions.
IntActiP42586. 1 interaction.
MINTiMINT-4103861.

Proteomic databases

PaxDbiP42586.
PRIDEiP42586.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067075; ENSMUSP00000069666; ENSMUSG00000027434.
GeneIDi18088.
KEGGimmu:18088.
UCSCiuc008msu.1. mouse.

Organism-specific databases

CTDi4821.
MGIiMGI:97347. Nkx2-2.

Phylogenomic databases

eggNOGiNOG310976.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP42586.
KOiK08029.
PhylomeDBiP42586.
TreeFamiTF351204.

Enzyme and pathway databases

ReactomeiREACT_214529. Regulation of gene expression in beta cells.
REACT_221082. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Miscellaneous databases

NextBioi293225.
PROiP42586.
SOURCEiSearch...

Gene expression databases

BgeeiP42586.
ExpressionAtlasiP42586. baseline and differential.
GenevestigatoriP42586.

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. "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. 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.

Entry informationi

Entry nameiNKX22_MOUSE
AccessioniPrimary (citable) accession number: P42586
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 1, 1996
Last modified: January 7, 2015
This is version 125 of the entry and version 2 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.