NKX26_MOUSE
ID NKX26_MOUSE Reviewed; 289 AA.
AC P43688;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Homeobox protein Nkx-2.6;
DE AltName: Full=Homeobox protein NK-2 homolog F;
GN Name=Nkx2-6; Synonyms=Nkx-2.6, Nkx2f;
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], AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ;
RX PubMed=9545560; DOI=10.1016/s0925-4773(98)00037-9;
RA Biben C., Hatzistavrou T., Wang C.-C., Harvey R.P.;
RT "Expression of NK-2 class homeobox gene Nkx2-6 in foregut endoderm and
RT heart.";
RL Mech. Dev. 73:125-127(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 123-214.
RC TISSUE=Heart;
RX PubMed=7904557; DOI=10.1242/dev.119.2.419;
RA Lints T.J., Parsons L.M., Hartley L., Lyons I., Harvey R.P.;
RT "Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor
RT cells and their myogenic descendants.";
RL Development 119:419-431(1993).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=9486544; DOI=10.1016/s0925-4773(97)00174-3;
RA Nikolova M., Chen X., Lufkin T.;
RT "Nkx2.6 expression is transiently and specifically restricted to the
RT branchial region of pharyngeal-stage mouse embryos.";
RL Mech. Dev. 69:215-218(1997).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10733590; DOI=10.1128/mcb.20.8.2874-2879.2000;
RA Tanaka M., Yamasaki N., Izumo S.;
RT "Phenotypic characterization of the murine Nkx2.6 homeobox gene by gene
RT targeting.";
RL Mol. Cell. Biol. 20:2874-2879(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11390666; DOI=10.1128/mcb.21.13.4391-4398.2001;
RA Tanaka M., Schinke M., Liao H.S., Yamasaki N., Izumo S.;
RT "Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for
RT development of the pharynx.";
RL Mol. Cell. Biol. 21:4391-4398(2001).
CC -!- FUNCTION: Acts as a transcriptional activator (By similarity). In
CC conjunction with NKX2-5, may play a role in both pharyngeal and cardiac
CC embryonic development (PubMed:10733590, PubMed:11390666).
CC {ECO:0000250|UniProtKB:A6NCS4, ECO:0000269|PubMed:10733590,
CC ECO:0000269|PubMed:11390666}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Not detected in any neonate or adult tissues.
CC {ECO:0000269|PubMed:10733590}.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing gut endoderm, cardiac
CC progenitors and heart. Expression restricted to the very narrow
CC development period between stages 8.0 and 11.5 dpc. First detected at
CC 8.0 dpc in the endoderm of the lateral walls and lip of the forming
CC foregut pocket, directly juxtaposed to cardiogenic mesoderm. At 8.5
CC dpc, expressed in the forming pharynx, predominantly in its lateral
CC aspects where pouches will form. From 8.5 to 11.5 dpc, expressed in the
CC ventrolateral endoderm of all forming pouches, as well as in juxtaposed
CC arch ectoderm and mesenchyme. Expression levels decrease as pouches
CC matured. Also expressed in the ventral hindgut endoderm from 9.5 dpc
CC and in a short segment at the foregut-midgut junction spanning the
CC proximal parts of the common bile and pancreatic ducts.
CC {ECO:0000269|PubMed:9486544, ECO:0000269|PubMed:9545560}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype; possibly due to the
CC redundancy with NKX2-6. Mutant mice are viable and fertile. No obvious
CC abnormalities in the caudal pharyngeal pouch derivatives (thymus,
CC parathyroid glands, and thyroid gland), heart and gut. In NKX2-5 and
CC NKX2-6 double mutants, the pharynx does not form properly and the
CC development of the atrium is less advanced.
CC {ECO:0000269|PubMed:10733590, ECO:0000269|PubMed:11390666}.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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DR EMBL; AF045150; AAC15674.1; -; mRNA.
DR CCDS; CCDS56968.1; -.
DR RefSeq; NP_035050.2; NM_010920.2.
DR AlphaFoldDB; P43688; -.
DR SMR; P43688; -.
DR STRING; 10090.ENSMUSP00000049898; -.
DR iPTMnet; P43688; -.
DR PhosphoSitePlus; P43688; -.
DR PaxDb; P43688; -.
DR PRIDE; P43688; -.
DR ProteomicsDB; 287430; -.
DR Antibodypedia; 58740; 175 antibodies from 27 providers.
DR DNASU; 18092; -.
DR Ensembl; ENSMUST00000062437; ENSMUSP00000049898; ENSMUSG00000044186.
DR GeneID; 18092; -.
DR KEGG; mmu:18092; -.
DR UCSC; uc007umb.2; mouse.
DR CTD; 137814; -.
DR MGI; MGI:97351; Nkx2-6.
DR VEuPathDB; HostDB:ENSMUSG00000044186; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000162737; -.
DR HOGENOM; CLU_049543_0_0_1; -.
DR InParanoid; P43688; -.
DR OMA; GRSEQPK; -.
DR OrthoDB; 1191455at2759; -.
DR PhylomeDB; P43688; -.
DR TreeFam; TF351204; -.
DR BioGRID-ORCS; 18092; 2 hits in 72 CRISPR screens.
DR PRO; PR:P43688; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P43688; protein.
DR Bgee; ENSMUSG00000044186; Expressed in pharyngeal arch 3 and 52 other tissues.
DR Genevisible; P43688; MM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; ISO: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; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IGI:MGI.
DR GO; GO:0055014; P:atrial cardiac muscle cell development; IEP:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0048565; P:digestive tract development; IEP:BHF-UCL.
DR GO; GO:0035050; P:embryonic heart tube development; IEP:BHF-UCL.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IGI:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; IGI:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IGI:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0021854; P:hypothalamus development; IEP:BHF-UCL.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IGI:MGI.
DR GO; GO:0060039; P:pericardium development; IEP:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; IGI:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043586; P:tongue development; IEP:BHF-UCL.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEP:BHF-UCL.
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..289
FT /note="Homeobox protein Nkx-2.6"
FT /id="PRO_0000048942"
FT DNA_BIND 123..182
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 75..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 289 AA; 31597 MW; DBF8740A39CC0805 CRC64;
MLSSPVASTP FSVADILRLE CQQKDSKTLS QWELHRNPVK PRYLRMNQES GWFESSDRAQ
AVPFRCTWET VLEMGSNPVG EPQTPPGTIS RLGARNPMTD RGVGNLSGDM RRGGPVSTRT
RPQRKSRVLF SQAQVLALER RFKQQRYLTA PEREHLASAL QLTSTQVKIW FQNRRYKSKS
QRQDQTLELA GHPLAPRRVA VPVLVLDGKP CLDPDVAAFL GPYKATSPYS CFGGYAGTPY
DASYASRCTS ASAGPGPLTP LASSGFSPGG QSAAPQGHLP ATPQGVTAW