NKX22_MOUSE
ID NKX22_MOUSE Reviewed; 273 AA.
AC P42586;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Homeobox protein Nkx-2.2;
DE AltName: Full=Homeobox protein NK-2 homolog B;
GN Name=Nkx2-2; Synonyms=Nkx-2.2, Nkx2b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7939711; DOI=10.1126/science.7939711;
RA Rubenstein J.L., Martinez S., Shimamura K., Puelles L.;
RT "The embryonic vertebrate forebrain: the prosomeric model.";
RL Science 266:578-580(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8654958; DOI=10.1016/0378-1119(95)00745-8;
RA Hartigan D.J., Rubenstein J.L.;
RT "The cDNA sequence of murine Nkx-2.2.";
RL Gene 168:271-272(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-196.
RX PubMed=1346742; DOI=10.1016/0896-6273(92)90291-k;
RA Price M., Lazzaro D., Pohl T., Mattei M.-G., Ruether U., Olivo J.-C.,
RA Duboule D., di Lauro R.;
RT "Regional expression of the homeobox gene Nkx-2.2 in the developing
RT mammalian forebrain.";
RL Neuron 8:241-255(1992).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11076772; DOI=10.1242/dev.127.24.5533;
RA Sander M., Sussel L., Conners J., Scheel D., Kalamaras J., Dela Cruz F.,
RA Schwitzgebel V., Hayes-Jordan A., German M.;
RT "Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of
RT beta-cell formation in the pancreas.";
RL Development 127:5533-5540(2000).
RN [5]
RP INTERACTION WITH OLIG2, AND SUBCELLULAR LOCATION.
RX PubMed=14573534; DOI=10.1523/jneurosci.23-29-09547.2003;
RA Sun T., Dong H., Wu L., Kane M., Rowitch D.H., Stiles C.D.;
RT "Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors
RT in developing neural tube associated with formation of a specific physical
RT complex.";
RL J. Neurosci. 23:9547-9556(2003).
RN [6]
RP FUNCTION, ASSOCIATION WITH CHROMATIN, DNA-BINDING, AND MUTAGENESIS OF
RP LYS-184.
RX PubMed=19759004; DOI=10.1074/jbc.m109.048694;
RA Anderson K.R., Torres C.A., Solomon K., Becker T.C., Newgard C.B.,
RA Wright C.V., Hagman J., Sussel L.;
RT "Cooperative transcriptional regulation of the essential pancreatic islet
RT gene NeuroD1 (beta2) by Nkx2.2 and neurogenin 3.";
RL J. Biol. Chem. 284:31236-31248(2009).
CC -!- FUNCTION: Transcriptional activator involved in the development of
CC insulin-producting beta cells in the endocrine pancreas
CC (PubMed:11076772). May also be involved in specifying diencephalic
CC neuromeric boundaries, and in controlling the expression of genes that
CC play a role in axonal guidance. Binds to elements within the NEUROD1
CC promoter (PubMed:19759004). {ECO:0000269|PubMed:11076772,
CC ECO:0000269|PubMed:19759004}.
CC -!- SUBUNIT: Interacts with OLIG2. {ECO:0000269|PubMed:14573534}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:14573534}.
CC -!- TISSUE SPECIFICITY: Expressed in restricted areas of the developing
CC CNS: the hindbrain and forebrain, and pancreas.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis.
CC -!- DOMAIN: The homeodomain is essential for interaction with OLIG2.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos do not form any insulin-expressing
CC cells in the pancreas throughout development, and instead accumulate
CC incompletely differentiated beta cells (PubMed:11076772). Simultaneous
CC knockout of NKX6-1 and NKX2-2 is not distinguable from the single NKX2-
CC 2 knockout (PubMed:11076772). {ECO:0000269|PubMed:11076772}.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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DR EMBL; U31566; AAA79303.1; -; mRNA.
DR EMBL; S83259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16834.1; -.
DR PIR; JC4634; JC4634.
DR RefSeq; NP_035049.1; NM_010919.2.
DR RefSeq; XP_006498961.1; XM_006498898.2.
DR RefSeq; XP_006498962.1; XM_006498899.2.
DR RefSeq; XP_006498963.1; XM_006498900.3.
DR RefSeq; XP_011237651.1; XM_011239349.2.
DR AlphaFoldDB; P42586; -.
DR SMR; P42586; -.
DR BioGRID; 201776; 4.
DR IntAct; P42586; 1.
DR STRING; 10090.ENSMUSP00000069666; -.
DR iPTMnet; P42586; -.
DR PhosphoSitePlus; P42586; -.
DR PaxDb; P42586; -.
DR PeptideAtlas; P42586; -.
DR PRIDE; P42586; -.
DR ProteomicsDB; 252901; -.
DR Antibodypedia; 908; 885 antibodies from 36 providers.
DR DNASU; 18088; -.
DR Ensembl; ENSMUST00000067075; ENSMUSP00000069666; ENSMUSG00000027434.
DR GeneID; 18088; -.
DR KEGG; mmu:18088; -.
DR UCSC; uc008msu.1; mouse.
DR CTD; 4821; -.
DR MGI; MGI:97347; Nkx2-2.
DR VEuPathDB; HostDB:ENSMUSG00000027434; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000159727; -.
DR HOGENOM; CLU_049543_0_2_1; -.
DR InParanoid; P42586; -.
DR OrthoDB; 1072653at2759; -.
DR PhylomeDB; P42586; -.
DR TreeFam; TF351204; -.
DR BioGRID-ORCS; 18088; 2 hits in 74 CRISPR screens.
DR PRO; PR:P42586; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P42586; protein.
DR Bgee; ENSMUSG00000027434; Expressed in islet of Langerhans and 88 other tissues.
DR ExpressionAtlas; P42586; baseline and differential.
DR Genevisible; P42586; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; IMP:MGI.
DR GO; GO:0048468; P:cell development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; IDA:MGI.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0048665; P:neuron fate specification; IMP:MGI.
DR GO; GO:0014003; P:oligodendrocyte development; IMP:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl.
DR GO; GO:0003326; P:pancreatic A cell fate commitment; IMP:MGI.
DR GO; GO:0003329; P:pancreatic PP cell fate commitment; IGI:MGI.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:MGI.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; IMP:MGI.
DR GO; GO:0021529; P:spinal cord oligodendrocyte cell differentiation; IMP:MGI.
DR GO; GO:0021530; P:spinal cord oligodendrocyte cell fate specification; IDA:MGI.
DR GO; GO:0003323; P:type B pancreatic cell development; IDA:MGI.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:MGI.
DR GO; GO:0003327; P:type B pancreatic cell fate commitment; IMP:MGI.
DR GO; GO:0060580; P:ventral spinal cord interneuron fate determination; IMP:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..273
FT /note="Homeobox protein Nkx-2.2"
FT /id="PRO_0000048931"
FT DNA_BIND 128..187
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..35
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 184
FT /note="K->I: Inhibits DNA-binding activity and
FT transcriptional activation of NEUROD1 expression."
FT /evidence="ECO:0000269|PubMed:19759004"
SQ SEQUENCE 273 AA; 30126 MW; 1F3DBB8127667F19 CRC64;
MSLTNTKTGF SVKDILDLPD TNDEDGSVAE GPEEESEGPE PAKRAGPLGQ GALDAVQSLP
LKSPFYDSSD NPYTRWLAST EGLQYSLHGL AASAPPQDSS SKSPEPSADE SPDNDKETQG
GGGDAGKKRK RRVLFSKAQT YELERRFRQQ RYLSAPEREH LASLIRLTPT QVKIWFQNHR
YKMKRARAEK GMEVTPLPSP RRVAVPVLVR DGKPCHALKA QDLAAATFQA GIPFSAYSAQ
SLQHMQYNAQ YSSASTPQYP TAHPLVQAQQ WTW
