NKX22_HUMAN
ID NKX22_HUMAN Reviewed; 273 AA.
AC O95096;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Homeobox protein Nkx-2.2;
DE AltName: Full=Homeobox protein NK-2 homolog B;
GN Name=NKX2-2; Synonyms=NKX2.2, NKX2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9703340; DOI=10.2337/diab.47.8.1356;
RA Furuta H., Horikawa Y., Iwasaki N., Hara M., Sussel L., le Beau M.M.,
RA Davis E.M., Ogata M., Iwamoto Y., German M.S., Bell G.I.;
RT "Beta-cell transcription factors and diabetes: mutations in the coding
RT region of the BETA2/NeuroD1 (NEUROD1) and Nkx2.2 (NKX2B) genes are not
RT associated with maturity-onset diabetes of the young in Japanese.";
RL Diabetes 47:1356-1358(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Transcriptional activator involved in the development of
CC insulin-producting beta cells in the endocrine pancreas (By
CC similarity). May also be involved in specifying diencephalic neuromeric
CC boundaries, and in controlling the expression of genes that play a role
CC in axonal guidance. Binds to elements within the NEUROD1 promoter (By
CC similarity). {ECO:0000250|UniProtKB:P42586}.
CC -!- SUBUNIT: Interacts with OLIG2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DOMAIN: The homeodomain is essential for interaction with OLIG2.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NKX22ID44177ch20p11.html";
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DR EMBL; AF019415; AAC83132.1; -; Genomic_DNA.
DR EMBL; AF019414; AAC83132.1; JOINED; Genomic_DNA.
DR EMBL; AL133325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075092; AAH75092.1; -; mRNA.
DR EMBL; BC075093; AAH75093.1; -; mRNA.
DR CCDS; CCDS13145.1; -.
DR RefSeq; NP_002500.1; NM_002509.3.
DR AlphaFoldDB; O95096; -.
DR SMR; O95096; -.
DR BioGRID; 110886; 2.
DR IntAct; O95096; 1.
DR MINT; O95096; -.
DR STRING; 9606.ENSP00000366347; -.
DR iPTMnet; O95096; -.
DR PhosphoSitePlus; O95096; -.
DR BioMuta; NKX2-2; -.
DR MassIVE; O95096; -.
DR PaxDb; O95096; -.
DR PeptideAtlas; O95096; -.
DR PRIDE; O95096; -.
DR Antibodypedia; 908; 885 antibodies from 36 providers.
DR DNASU; 4821; -.
DR Ensembl; ENST00000377142.5; ENSP00000366347.4; ENSG00000125820.6.
DR GeneID; 4821; -.
DR KEGG; hsa:4821; -.
DR MANE-Select; ENST00000377142.5; ENSP00000366347.4; NM_002509.4; NP_002500.1.
DR UCSC; uc002wsi.4; human.
DR CTD; 4821; -.
DR DisGeNET; 4821; -.
DR GeneCards; NKX2-2; -.
DR HGNC; HGNC:7835; NKX2-2.
DR HPA; ENSG00000125820; Tissue enriched (brain).
DR MIM; 604612; gene.
DR neXtProt; NX_O95096; -.
DR OpenTargets; ENSG00000125820; -.
DR PharmGKB; PA31642; -.
DR VEuPathDB; HostDB:ENSG00000125820; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000159727; -.
DR HOGENOM; CLU_049543_0_2_1; -.
DR InParanoid; O95096; -.
DR OMA; NTDNPYT; -.
DR OrthoDB; 1072653at2759; -.
DR PhylomeDB; O95096; -.
DR TreeFam; TF351204; -.
DR PathwayCommons; O95096; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR Reactome; R-HSA-210746; Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.
DR SignaLink; O95096; -.
DR BioGRID-ORCS; 4821; 12 hits in 1065 CRISPR screens.
DR ChiTaRS; NKX2-2; human.
DR GeneWiki; NKX2-2; -.
DR GenomeRNAi; 4821; -.
DR Pharos; O95096; Tbio.
DR PRO; PR:O95096; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O95096; protein.
DR Bgee; ENSG00000125820; Expressed in inferior vagus X ganglion and 67 other tissues.
DR Genevisible; O95096; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl.
DR GO; GO:0003326; P:pancreatic A cell fate commitment; IEA:Ensembl.
DR GO; GO:0003329; P:pancreatic PP cell fate commitment; IEA:Ensembl.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; IEA:Ensembl.
DR GO; GO:0021530; P:spinal cord oligodendrocyte cell fate specification; IEA:Ensembl.
DR GO; GO:0003323; P:type B pancreatic cell development; IEA:Ensembl.
DR GO; GO:0003327; P:type B pancreatic cell fate commitment; IEA:Ensembl.
DR GO; GO:0060580; P:ventral spinal cord interneuron fate determination; IEA:Ensembl.
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 2: Evidence at transcript 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_0000048929"
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 90..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 108..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 273 AA; 30133 MW; 91BDA220BAFA63D1 CRC64;
MSLTNTKTGF SVKDILDLPD TNDEEGSVAE GPEEENEGPE PAKRAGPLGQ GALDAVQSLP
LKNPFYDSSD NPYTRWLAST EGLQYSLHGL AAGAPPQDSS SKSPEPSADE SPDNDKETPG
GGGDAGKKRK RRVLFSKAQT YELERRFRQQ RYLSAPEREH LASLIRLTPT QVKIWFQNHR
YKMKRARAEK GMEVTPLPSP RRVAVPVLVR DGKPCHALKA QDLAAATFQA GIPFSAYSAQ
SLQHMQYNAQ YSSASTPQYP TAHPLVQAQQ WTW
