NKX21_MOUSE
ID NKX21_MOUSE Reviewed; 372 AA.
AC P50220;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Homeobox protein Nkx-2.1;
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|MGI:MGI:108067}; Synonyms=Nkx-2.1, Titf1, Ttf1;
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 [GENOMIC DNA].
RC STRAIN=129/Sv; TISSUE=Liver;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=22955271; DOI=10.1074/jbc.m112.408401;
RA Varma S., Cao Y., Tagne J.B., Lakshminarayanan M., Li J., Friedman T.B.,
RA Morell R.J., Warburton D., Kotton D.N., Ramirez M.I.;
RT "The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a
RT regulatory loop that coordinates lung epithelial cell morphogenesis and
RT differentiation.";
RL J. Biol. Chem. 287:37282-37295(2012).
RN [4]
RP FUNCTION.
RX PubMed=22356123; DOI=10.1111/j.1365-2826.2012.02302.x;
RA Matagne V., Kim J.G., Ryu B.J., Hur M.K., Kim M.S., Kim K., Park B.S.,
RA Damante G., Smiley G., Lee B.J., Ojeda S.R.;
RT "Thyroid transcription factor 1, a homeodomain containing transcription
RT factor, contributes to regulating periodic oscillations in GnRH gene
RT expression.";
RL J. Neuroendocrinol. 24:916-929(2012).
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 (PubMed:22955271). Activates the transcription of GNRHR and plays a
CC role in enhancing the circadian oscillation of its gene expression.
CC Represses the transcription of the circadian transcriptional repressor
CC NR1D1 (PubMed:22356123). {ECO:0000250|UniProtKB:P23441,
CC ECO:0000269|PubMed:22356123, ECO:0000269|PubMed:22955271}.
CC -!- SUBUNIT: Interacts with WWTR1. {ECO:0000250|UniProtKB:P43699}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22955271}.
CC -!- TISSUE SPECIFICITY: Thyroid, lung and brain.
CC -!- DEVELOPMENTAL STAGE: Expressed in lung at least from to 9.5 dpc to
CC adulthood. {ECO:0000269|PubMed:22955271}.
CC -!- PTM: Phosphorylated on serine residues by STK3/MST2. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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DR EMBL; U19755; AAA86100.1; -; Genomic_DNA.
DR EMBL; BC080868; AAH80868.1; -; mRNA.
DR CCDS; CCDS25922.1; -.
DR PIR; S53724; S53724.
DR RefSeq; NP_033411.3; NM_009385.3.
DR AlphaFoldDB; P50220; -.
DR BMRB; P50220; -.
DR SMR; P50220; -.
DR BioGRID; 204207; 12.
DR IntAct; P50220; 9.
DR STRING; 10090.ENSMUSP00000001536; -.
DR iPTMnet; P50220; -.
DR PhosphoSitePlus; P50220; -.
DR MaxQB; P50220; -.
DR PaxDb; P50220; -.
DR PRIDE; P50220; -.
DR ProteomicsDB; 287428; -.
DR Antibodypedia; 3519; 1099 antibodies from 45 providers.
DR DNASU; 21869; -.
DR Ensembl; ENSMUST00000001536; ENSMUSP00000001536; ENSMUSG00000001496.
DR Ensembl; ENSMUST00000178477; ENSMUSP00000136103; ENSMUSG00000001496.
DR GeneID; 21869; -.
DR KEGG; mmu:21869; -.
DR UCSC; uc007npf.3; mouse.
DR CTD; 7080; -.
DR MGI; MGI:108067; Nkx2-1.
DR VEuPathDB; HostDB:ENSMUSG00000001496; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000161107; -.
DR HOGENOM; CLU_052416_0_0_1; -.
DR InParanoid; P50220; -.
DR OMA; PPYQETM; -.
DR OrthoDB; 1209625at2759; -.
DR PhylomeDB; P50220; -.
DR TreeFam; TF351204; -.
DR BioGRID-ORCS; 21869; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Nkx2-1; mouse.
DR PRO; PR:P50220; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P50220; protein.
DR Bgee; ENSMUSG00000001496; Expressed in future forebrain and 83 other tissues.
DR Genevisible; P50220; MM.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA: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; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0017025; F:TBP-class protein binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0021795; P:cerebral cortex cell migration; IMP:MGI.
DR GO; GO:0021892; P:cerebral cortex GABAergic interneuron differentiation; IMP:MGI.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IMP:MGI.
DR GO; GO:0060486; P:club cell differentiation; IGI:MGI.
DR GO; GO:0031128; P:developmental induction; IMP:MGI.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0007631; P:feeding behavior; ISO:MGI.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IMP:MGI.
DR GO; GO:0021879; P:forebrain neuron differentiation; IMP:MGI.
DR GO; GO:0021877; P:forebrain neuron fate commitment; IMP:MGI.
DR GO; GO:0097154; P:GABAergic neuron differentiation; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0021759; P:globus pallidus development; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0042538; P:hyperosmotic salinity response; ISO:MGI.
DR GO; GO:0021854; P:hypothalamus development; IMP:MGI.
DR GO; GO:1904936; P:interneuron migration; IMP:MGI.
DR GO; GO:0033327; P:Leydig cell differentiation; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0060430; P:lung saccule development; IGI:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0048663; P:neuron fate commitment; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0007389; P:pattern specification process; IGI:MGI.
DR GO; GO:0006644; P:phospholipid metabolic process; IGI:MGI.
DR GO; GO:0021983; P:pituitary gland development; IMP:MGI.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0002016; P:regulation of blood volume by renin-angiotensin; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0022029; P:telencephalon cell migration; IMP:MGI.
DR GO; GO:0021537; P:telencephalon development; IMP:MGI.
DR GO; GO:0030878; P:thyroid gland development; IMP:MGI.
DR GO; GO:0060510; P:type II pneumocyte differentiation; IGI: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 2: Evidence at transcript level;
KW Activator; Biological rhythms; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..372
FT /note="Homeobox protein Nkx-2.1"
FT /id="PRO_0000049344"
FT DNA_BIND 161..220
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 219..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23441"
SQ SEQUENCE 372 AA; 38570 MW; 377B5CE9B709412F CRC64;
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPA AAMQQHAVGH
HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY QDTMRNSASG PGWYGANPDP
RFPAISRFMG PASGMNMSGM GGLGSLGDVS KNMAPLPSAP RRKRRVLFSQ AQVYELERRF
KQQKYLSAPE REHLASMIHL TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG
GGAGCPQQQQ AQQQSPRRVA VPVLVKDGKP CQAGAPAPGA ASLQSHAQQQ AQQQAQAAQA
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAG LQGQVSSLSH LNSSGSDYGA
MSCSTLLYGR TW
