ID NKX21_HUMAN Reviewed; 371 AA.
AC P43699; D3DSA3; O14954; O14955; Q7KZF6; Q9BRJ8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 27-MAR-2024, entry version 214.
DE RecName: Full=Homeobox protein Nkx-2.1;
DE AltName: Full=Homeobox protein NK-2 homolog A;
DE AltName: Full=Thyroid nuclear factor 1;
DE AltName: Full=Thyroid transcription factor 1;
DE Short=TTF-1;
DE AltName: Full=Thyroid-specific enhancer-binding protein;
DE Short=T/EBP;
GN Name=NKX2-1 {ECO:0000312|HGNC:HGNC:11825}; Synonyms=NKX2A, TITF1, TTF1;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=7711079; DOI=10.1016/0167-4781(95)00033-d;
RA Oguchi H., Pan Y.-T., Kimura S.;
RT "The complete nucleotide sequence of the mouse thyroid-specific enhancer-
RT binding protein (T/EBP) gene: extensive identity of the deduced amino acid
RT sequence with the human protein.";
RL Biochim. Biophys. Acta 1261:304-306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=7711080; DOI=10.1016/0167-4781(95)00034-e;
RA Saiardi A., Tassi V., de Filippis V., Civitareale D.;
RT "Cloning and sequence analysis of human thyroid transcription factor 1.";
RL Biochim. Biophys. Acta 1261:307-310(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=7713914; DOI=10.1074/jbc.270.14.8108;
RA Ikeda K., Clark J.C., Shaw-White J.R., Stahlman M.T., Boutell C.J.,
RA Whitsett J.A.;
RT "Gene structure and expression of human thyroid transcription factor-1 in
RT respiratory epithelial cells.";
RL J. Biol. Chem. 270:8108-8114(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung;
RX PubMed=9545595; DOI=10.1016/s0167-4781(97)00210-8;
RA Hamdan H., Liu H., Li C., Jones C., Lee M., deLemos R., Minoo P.;
RT "Structure of the human Nkx2.1 gene.";
RL Biochim. Biophys. Acta 1396:336-348(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RA Endo T., Ohno M., Nakazato M.;
RT "Cloning of the human TTF-1 gene.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lung;
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).
RN [10]
RP INTERACTION WITH WWTR1.
RX PubMed=19010321; DOI=10.1016/j.yexcr.2008.10.016;
RA Di Palma T., D'Andrea B., Liguori G.L., Liguoro A., de Cristofaro T.,
RA Del Prete D., Pappalardo A., Mascia A., Zannini M.;
RT "TAZ is a coactivator for Pax8 and TTF-1, two transcription factors
RT involved in thyroid differentiation.";
RL Exp. Cell Res. 315:162-175(2009).
RN [11]
RP INVOLVEMENT IN NMTC1, VARIANT NMTC1 VAL-339, AND CHARACTERIZATION OF
RP VARIANT NMTC1 VAL-339.
RX PubMed=19176457; DOI=10.1093/jnci/djn471;
RA Ngan E.S., Lang B.H., Liu T., Shum C.K., So M.T., Lau D.K., Leon T.Y.,
RA Cherny S.S., Tsai S.Y., Lo C.Y., Khoo U.S., Tam P.K., Garcia-Barcelo M.M.;
RT "A germline mutation (A339V) in thyroid transcription factor-1 (TITF-
RT 1/NKX2.1) in patients with multinodular goiter and papillary thyroid
RT carcinoma.";
RL J. Natl. Cancer Inst. 101:162-175(2009).
RN [12]
RP VARIANTS BHC LEU-208 AND SER-213, AND INVOLVEMENT IN BHC.
RX PubMed=11971878; DOI=10.1093/hmg/11.8.971;
RA Breedveld G.J., van Dongen J.W.F., Danesino C., Guala A., Percy A.K.,
RA Dure L.S., Harper P., Lazarou L.P., van der Linde H., Joosse M.,
RA Grueters A., MacDonald M.E., de Vries B.B.A., Arts W.F.M., Oostra B.A.,
RA Krude H., Heutink P.;
RT "Mutations in TITF-1 are associated with benign hereditary chorea.";
RL Hum. Mol. Genet. 11:971-979(2002).
RN [13]
RP INVOLVEMENT IN CAHTP.
RX PubMed=11854318; DOI=10.1172/jci14192;
RA Pohlenz J., Dumitrescu A., Zundel D., Martine U., Schoenberger W., Koo E.,
RA Weiss R.E., Cohen R.N., Kimura S., Refetoff S.;
RT "Partial deficiency of thyroid transcription factor 1 produces
RT predominantly neurological defects in humans and mice.";
RL J. Clin. Invest. 109:469-473(2002).
RN [14]
RP VARIANT CAHTP PHE-205.
RX PubMed=11854319; DOI=10.1172/jci14341;
RA Krude H., Schuetz B., Biebermann H., von Moers A., Schnabel D., Neitzel H.,
RA Toennies H., Weise D., Lafferty A., Schwarz S., DeFelice M.,
RA von Deimling A., van Landeghem F., DiLauro R., Grueters A.;
RT "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human
RT NKX2-1 haploinsufficiency.";
RL J. Clin. Invest. 109:475-480(2002).
RN [15]
RP INVOLVEMENT IN CAHTP.
RX PubMed=15289765; DOI=10.1016/j.jpeds.2004.04.011;
RA Doyle D.A., Gonzalez I., Thomas B., Scavina M.;
RT "Autosomal dominant transmission of congenital hypothyroidism, neonatal
RT respiratory distress, and ataxia caused by a mutation of NKX2-1.";
RL J. Pediatr. 145:190-193(2004).
RN [16]
RP INVOLVEMENT IN CAHTP AND IN BHC.
RX PubMed=15955952; DOI=10.1212/01.wnl.0000164000.75046.cc;
RA Asmus F., Horber V., Pohlenz J., Schwabe D., Zimprich A., Munz M.,
RA Schoening M., Gasser T.;
RT "A novel TITF-1 mutation causes benign hereditary chorea with response to
RT levodopa.";
RL Neurology 64:1952-1954(2005).
RN [17]
RP VARIANT BHC PRO-179.
RX PubMed=24453141; DOI=10.1177/0883073813518243;
RA Williamson S., Kirkpatrick M., Greene S., Goudie D.;
RT "A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and
RT choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome.";
RL J. Child Neurol. 29:666-669(2014).
RN [18]
RP VARIANTS CAHTP ARG-203 AND PHE-205.
RX PubMed=24714694; DOI=10.1136/jmedgenet-2013-102248;
RA Thorwarth A., Schnittert-Huebener S., Schrumpf P., Mueller I., Jyrch S.,
RA Dame C., Biebermann H., Kleinau G., Katchanov J., Schuelke M., Ebert G.,
RA Steininger A., Boennemann C., Brockmann K., Christen H.J., Crock P.,
RA deZegher F., Griese M., Hewitt J., Ivarsson S., Huebner C., Kapelari K.,
RA Plecko B., Rating D., Stoeva I., Ropers H.H., Grueters A., Ullmann R.,
RA Krude H.;
RT "Comprehensive genotyping and clinical characterisation reveal 27 novel
RT NKX2-1 mutations and expand the phenotypic spectrum.";
RL J. Med. Genet. 51:375-387(2014).
RN [19]
RP VARIANTS BHC HIS-172 AND SER-208, AND CHARACTERIZATION OF VARIANTS BHC
RP HIS-172 AND SER-208.
RX PubMed=26723978; DOI=10.1016/j.jns.2015.11.050;
RA Provenzano C., Zamboni M., Veneziano L., Mantuano E., Garavaglia B.,
RA Zorzi G., Pagonabarraga J., Giunti P., Civitareale D.;
RT "Functional characterization of two novel mutations in TTF-1/NKX2.1
RT homeodomain in patients with benign hereditary chorea.";
RL J. Neurol. Sci. 360:78-83(2016).
CC -!- FUNCTION: Transcription factor that binds and activates the promoter of
CC thyroid specific genes such as thyroglobulin, thyroperoxidase, and
CC thyrotropin receptor. Crucial in the maintenance of the thyroid
CC differentiation phenotype. May play a role in lung development and
CC surfactant homeostasis. Forms a regulatory loop with GRHL2 that
CC coordinates lung epithelial cell morphogenesis and differentiation.
CC Activates the transcription of GNRHR and plays a role in enhancing the
CC circadian oscillation of its gene expression. Represses the
CC transcription of the circadian transcriptional repressor NR1D1 (By
CC similarity). {ECO:0000250|UniProtKB:P23441,
CC ECO:0000250|UniProtKB:P50220}.
CC -!- SUBUNIT: Interacts with WWTR1. {ECO:0000269|PubMed:19010321}.
CC -!- INTERACTION:
CC P43699; Q9P031: CCDC59; NbExp=4; IntAct=EBI-1391923, EBI-1047110;
CC P43699; P16333: NCK1; NbExp=2; IntAct=EBI-1391923, EBI-389883;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50220}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43699-1; Sequence=Displayed;
CC Name=3;
CC IsoId=P43699-3; Sequence=VSP_037890;
CC -!- TISSUE SPECIFICITY: Thyroid and lung.
CC -!- PTM: Phosphorylated on serine residues by STK3/MST2. {ECO:0000250}.
CC -!- DISEASE: Chorea, hereditary benign (BHC) [MIM:118700]: A rare autosomal
CC dominant movement disorder, defined by early onset in childhood, a
CC stable or non-progressive course of chorea, and no mental
CC deterioration. Chorea is characterized by involuntary, forcible, rapid,
CC jerky movements that may be subtle or become confluent, markedly
CC altering normal patterns of movement. {ECO:0000269|PubMed:11971878,
CC ECO:0000269|PubMed:15955952, ECO:0000269|PubMed:24453141,
CC ECO:0000269|PubMed:26723978}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Choreoathetosis and congenital hypothyroidism with or without
CC pulmonary dysfunction (CAHTP) [MIM:610978]: An autosomal dominant
CC disorder that manifests in infancy with neurological disturbances,
CC hypothyroidism, and respiratory problems. It is characterized by
CC movement abnormalities beginning with muscular hypotonia followed by
CC the development of chorea, athetosis, dystonia, ataxia, and dysarthria.
CC {ECO:0000269|PubMed:11854318, ECO:0000269|PubMed:11854319,
CC ECO:0000269|PubMed:15289765, ECO:0000269|PubMed:15955952,
CC ECO:0000269|PubMed:24714694}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Thyroid cancer, non-medullary, 1 (NMTC1) [MIM:188550]: A form
CC of non-medullary thyroid cancer (NMTC), a cancer characterized by
CC tumors originating from the thyroid follicular cells. NMTCs represent
CC approximately 95% of all cases of thyroid cancer and are classified
CC into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
CC {ECO:0000269|PubMed:19176457}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06221.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA23527.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/44015/NKX2-1";
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DR EMBL; U19756; AAA86099.1; -; mRNA.
DR EMBL; X82850; CAA58053.1; -; mRNA.
DR EMBL; U19816; AAC50125.1; -; Genomic_DNA.
DR EMBL; U33749; AAB52381.1; -; mRNA.
DR EMBL; U43203; AAA89066.1; -; mRNA.
DR EMBL; D50739; BAA23527.1; ALT_SEQ; Genomic_DNA.
DR EMBL; D50740; BAA23529.1; -; mRNA.
DR EMBL; BT009773; AAP88775.1; -; mRNA.
DR EMBL; AL132857; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65858.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65856.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65859.1; -; Genomic_DNA.
DR EMBL; BC006221; AAH06221.2; ALT_INIT; mRNA.
DR CCDS; CCDS41945.1; -. [P43699-3]
DR CCDS; CCDS9659.1; -. [P43699-1]
DR PIR; G02321; G02321.
DR RefSeq; NP_001073136.1; NM_001079668.2. [P43699-3]
DR RefSeq; NP_003308.1; NM_003317.3. [P43699-1]
DR AlphaFoldDB; P43699; -.
DR BMRB; P43699; -.
DR SMR; P43699; -.
DR BioGRID; 112936; 167.
DR ComplexPortal; CPX-6062; SMAD3-TTF-1 complex.
DR IntAct; P43699; 10.
DR MINT; P43699; -.
DR STRING; 9606.ENSP00000346879; -.
DR GlyGen; P43699; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P43699; -.
DR PhosphoSitePlus; P43699; -.
DR BioMuta; NKX2-1; -.
DR DMDM; 1174819; -.
DR MassIVE; P43699; -.
DR MaxQB; P43699; -.
DR PaxDb; 9606-ENSP00000346879; -.
DR PeptideAtlas; P43699; -.
DR ProteomicsDB; 55653; -. [P43699-1]
DR ProteomicsDB; 55654; -. [P43699-3]
DR Antibodypedia; 3519; 1307 antibodies from 45 providers.
DR DNASU; 7080; -.
DR Ensembl; ENST00000354822.7; ENSP00000346879.6; ENSG00000136352.20. [P43699-3]
DR Ensembl; ENST00000498187.6; ENSP00000429607.2; ENSG00000136352.20. [P43699-1]
DR Ensembl; ENST00000518149.5; ENSP00000428341.1; ENSG00000136352.20. [P43699-1]
DR Ensembl; ENST00000522719.4; ENSP00000429519.4; ENSG00000136352.20. [P43699-1]
DR GeneID; 7080; -.
DR KEGG; hsa:7080; -.
DR MANE-Select; ENST00000354822.7; ENSP00000346879.6; NM_001079668.3; NP_001073136.1. [P43699-3]
DR UCSC; uc001wtt.4; human. [P43699-1]
DR AGR; HGNC:11825; -.
DR CTD; 7080; -.
DR DisGeNET; 7080; -.
DR GeneCards; NKX2-1; -.
DR GeneReviews; NKX2-1; -.
DR HGNC; HGNC:11825; NKX2-1.
DR HPA; ENSG00000136352; Group enriched (lung, thyroid gland).
DR MalaCards; NKX2-1; -.
DR MIM; 118700; phenotype.
DR MIM; 188550; phenotype.
DR MIM; 600635; gene.
DR MIM; 610978; phenotype.
DR neXtProt; NX_P43699; -.
DR OpenTargets; ENSG00000136352; -.
DR Orphanet; 95713; Athyreosis.
DR Orphanet; 1429; Benign hereditary chorea.
DR Orphanet; 209905; Brain-lung-thyroid syndrome.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR PharmGKB; PA36531; -.
DR VEuPathDB; HostDB:ENSG00000136352; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000161107; -.
DR HOGENOM; CLU_052416_0_0_1; -.
DR InParanoid; P43699; -.
DR OMA; PPYQETM; -.
DR OrthoDB; 461623at2759; -.
DR PhylomeDB; P43699; -.
DR TreeFam; TF351204; -.
DR PathwayCommons; P43699; -.
DR SignaLink; P43699; -.
DR SIGNOR; P43699; -.
DR BioGRID-ORCS; 7080; 30 hits in 1162 CRISPR screens.
DR GeneWiki; NK2_homeobox_1; -.
DR GenomeRNAi; 7080; -.
DR Pharos; P43699; Tbio.
DR PRO; PR:P43699; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P43699; Protein.
DR Bgee; ENSG00000136352; Expressed in right lobe of thyroid gland and 82 other cell types or tissues.
DR Genevisible; P43699; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl.
DR GO; GO:0021892; P:cerebral cortex GABAergic interneuron differentiation; IEA:Ensembl.
DR GO; GO:0060486; P:club cell differentiation; IEA:Ensembl.
DR GO; GO:0031128; P:developmental induction; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEP:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEP:UniProtKB.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0021877; P:forebrain neuron fate commitment; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0021759; P:globus pallidus development; IMP:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
DR GO; GO:1904936; P:interneuron migration; IEA:Ensembl.
DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEP:UniProtKB.
DR GO; GO:0060430; P:lung saccule development; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:Ensembl.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IEP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0030878; P:thyroid gland development; IMP:UniProtKB.
DR GO; GO:0060510; P:type II pneumocyte differentiation; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR PANTHER; PTHR24340; HOMEOBOX PROTEIN NKX; 1.
DR PANTHER; PTHR24340:SF33; HOMEOBOX PROTEIN NKX-2.1; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; Homeodomain-like; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Biological rhythms;
KW Congenital hypothyroidism; Disease variant; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..371
FT /note="Homeobox protein Nkx-2.1"
FT /id="PRO_0000049343"
FT DNA_BIND 161..220
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 219..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23441"
FT VAR_SEQ 1
FT /note="M -> MWSGGSGKARGWEAAAGGRSSPGRLSRRRIM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9545595, ECO:0000303|Ref.6"
FT /id="VSP_037890"
FT VARIANT 172
FT /note="Q -> H (in BHC; decrease in DNA-binding; no effect
FT on transcription activation from thyroglobulin/TG, nor from
FT pulmonary surfactant-associated protein C/SFTPC gene
FT promoters)"
FT /evidence="ECO:0000269|PubMed:26723978"
FT /id="VAR_075209"
FT VARIANT 179
FT /note="R -> P (in BHC; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:24453141"
FT /id="VAR_077542"
FT VARIANT 203
FT /note="T -> R (in CAHTP)"
FT /evidence="ECO:0000269|PubMed:24714694"
FT /id="VAR_073040"
FT VARIANT 205
FT /note="V -> F (in CAHTP; dbSNP:rs137852692)"
FT /evidence="ECO:0000269|PubMed:11854319,
FT ECO:0000269|PubMed:24714694"
FT /id="VAR_034906"
FT VARIANT 208
FT /note="W -> L (in BHC; dbSNP:rs28936672)"
FT /evidence="ECO:0000269|PubMed:11971878"
FT /id="VAR_015188"
FT VARIANT 208
FT /note="W -> S (in BHC; loss of transcription activation)"
FT /evidence="ECO:0000269|PubMed:26723978"
FT /id="VAR_075210"
FT VARIANT 213
FT /note="R -> S (in BHC; dbSNP:rs28936671)"
FT /evidence="ECO:0000269|PubMed:11971878"
FT /id="VAR_015189"
FT VARIANT 339
FT /note="A -> V (in NMTC1; loss of transcription regulatory
FT region DNA binding; decreased transcription factor
FT activity, sequence-specific DNA binding; tested for the
FT thyroglobulin gene; results in dominant impairment of
FT thyroid-specific genes transcription and increased thyroid
FT cells proliferation; dbSNP:rs537209983)"
FT /evidence="ECO:0000269|PubMed:19176457"
FT /id="VAR_075769"
FT CONFLICT 49
FT /note="P -> H (in Ref. 5; BAA23527/BAA23529)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="H -> P (in Ref. 5; BAA23527/BAA23529)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="S -> T (in Ref. 5; BAA23527/BAA23529)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="R -> G (in Ref. 5; BAA23527/BAA23529)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 371 AA; 38596 MW; 5F1E3B40A1BBD862 CRC64;
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPT AAMQQHAVGH
HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY QDTMRNSASG PGWYGANPDP
RFPAISRFMG PASGMNMSGM GGLGSLGDVS KNMAPLPSAP RRKRRVLFSQ AQVYELERRF
KQQKYLSAPE REHLASMIHL TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG
GTGCPQQQQA QQQSPRRVAV PVLVKDGKPC QAGAPAPGAA SLQGHAQQQA QHQAQAAQAA
AAAISVGSGG AGLGAHPGHQ PGSAGQSPDL AHHAASPAAL QGQVSSLSHL NSSGSDYGTM
SCSTLLYGRT W
//
