NKX26_HUMAN
ID NKX26_HUMAN Reviewed; 301 AA.
AC A6NCS4;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Homeobox protein Nkx-2.6;
DE AltName: Full=Homeobox protein NK-2 homolog F;
GN Name=NKX2-6; Synonyms=NKX2F;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 64-214.
RX PubMed=15146197; DOI=10.1038/nbt971;
RA Brandenberger R., Wei H., Zhang S., Lei S., Murage J., Fisk G.J., Li Y.,
RA Xu C., Fang R., Guegler K., Rao M.S., Mandalam R., Lebkowski J.,
RA Stanton L.W.;
RT "Transcriptome characterization elucidates signaling networks that control
RT human ES cell growth and differentiation.";
RL Nat. Biotechnol. 22:707-716(2004).
RN [3]
RP VARIANT CTHM LEU-151, FUNCTION, CHARACTERIZATION OF VARIANT CTHM LEU-151,
RP AND INVOLVEMENT IN CTHM.
RX PubMed=15649947; DOI=10.1093/hmg/ddi055;
RA Heathcote K., Braybrook C., Abushaban L., Guy M., Khetyar M.E.,
RA Patton M.A., Carter N.D., Scambler P.J., Syrris P.;
RT "Common arterial trunk associated with a homeodomain mutation of NKX2.6.";
RL Hum. Mol. Genet. 14:585-593(2005).
RN [4]
RP VARIANT CTHM ALA-176.
RX PubMed=25195019; DOI=10.1016/j.ejmg.2014.08.005;
RA Zhao L., Ni S.H., Liu X.Y., Wei D., Yuan F., Xu L., Xin L., Li R.G.,
RA Qu X.K., Xu Y.J., Fang W.Y., Yang Y.Q., Qiu X.B.;
RT "Prevalence and spectrum of Nkx2.6 mutations in patients with congenital
RT heart disease.";
RL Eur. J. Med. Genet. 57:579-586(2014).
RN [5]
RP INVOLVEMENT IN CTHM.
RX PubMed=24421281; DOI=10.1136/jmedgenet-2013-102100;
RA Ta-Shma A., El-lahham N., Edvardson S., Stepensky P., Nir A., Perles Z.,
RA Gavri S., Golender J., Yaakobi-Simhayoff N., Shaag A., Rein A.J.,
RA Elpeleg O.;
RT "Conotruncal malformations and absent thymus due to a deleterious NKX2-6
RT mutation.";
RL J. Med. Genet. 51:268-270(2014).
RN [6]
RP VARIANT CTHM GLN-152.
RX PubMed=25380965; DOI=10.1007/s00246-014-1060-x;
RA Wang J., Mao J.H., Ding K.K., Xu W.J., Liu X.Y., Qiu X.B., Li R.G.,
RA Qu X.K., Xu Y.J., Huang R.T., Xue S., Yang Y.Q.;
RT "A novel NKX2.6 mutation associated with congenital ventricular septal
RT defect.";
RL Pediatr. Cardiol. 36:646-656(2015).
CC -!- FUNCTION: Acts as a transcriptional activator (PubMed:15649947). In
CC conjunction with NKX2-5, may play a role in both pharyngeal and cardiac
CC embryonic development. {ECO:0000250|UniProtKB:P43688,
CC ECO:0000269|PubMed:15649947}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group
CC of congenital heart defects involving the outflow tracts. Examples
CC include truncus arteriosus communis, double-outlet right ventricle and
CC transposition of great arteries. Truncus arteriosus communis is
CC characterized by a single outflow tract instead of a separate aorta and
CC pulmonary artery. In transposition of the great arteries, the aorta
CC arises from the right ventricle and the pulmonary artery from the left
CC ventricle. In double outlet of the right ventricle, both the pulmonary
CC artery and aorta arise from the right ventricle.
CC {ECO:0000269|PubMed:15649947, ECO:0000269|PubMed:24421281,
CC ECO:0000269|PubMed:25195019, ECO:0000269|PubMed:25380965}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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DR EMBL; AC012574; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CN272646; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001129743.2; NM_001136271.2.
DR AlphaFoldDB; A6NCS4; -.
DR SMR; A6NCS4; -.
DR BioGRID; 126485; 1.
DR IntAct; A6NCS4; 1.
DR STRING; 9606.ENSP00000320089; -.
DR GlyGen; A6NCS4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A6NCS4; -.
DR PhosphoSitePlus; A6NCS4; -.
DR BioMuta; NKX2-6; -.
DR EPD; A6NCS4; -.
DR jPOST; A6NCS4; -.
DR MassIVE; A6NCS4; -.
DR PaxDb; A6NCS4; -.
DR PeptideAtlas; A6NCS4; -.
DR PRIDE; A6NCS4; -.
DR ProteomicsDB; 858; -.
DR Antibodypedia; 58740; 175 antibodies from 27 providers.
DR DNASU; 137814; -.
DR Ensembl; ENST00000325017.4; ENSP00000320089.3; ENSG00000180053.8.
DR GeneID; 137814; -.
DR KEGG; hsa:137814; -.
DR MANE-Select; ENST00000325017.4; ENSP00000320089.3; NM_001136271.3; NP_001129743.2.
DR UCSC; uc011kzy.3; human.
DR CTD; 137814; -.
DR DisGeNET; 137814; -.
DR GeneCards; NKX2-6; -.
DR HGNC; HGNC:32940; NKX2-6.
DR HPA; ENSG00000180053; Tissue enhanced (salivary).
DR MalaCards; NKX2-6; -.
DR MIM; 217095; phenotype.
DR MIM; 611770; gene.
DR neXtProt; NX_A6NCS4; -.
DR OpenTargets; ENSG00000180053; -.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 1480; NON RARE IN EUROPE: Ventricular septal defect.
DR Orphanet; 3303; Tetralogy of Fallot.
DR Orphanet; 3384; Truncus arteriosus.
DR VEuPathDB; HostDB:ENSG00000180053; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000162737; -.
DR HOGENOM; CLU_049543_0_0_1; -.
DR InParanoid; A6NCS4; -.
DR OMA; GRSEQPK; -.
DR OrthoDB; 1191455at2759; -.
DR PhylomeDB; A6NCS4; -.
DR TreeFam; TF351204; -.
DR PathwayCommons; A6NCS4; -.
DR SignaLink; A6NCS4; -.
DR BioGRID-ORCS; 137814; 4 hits in 241 CRISPR screens.
DR GenomeRNAi; 137814; -.
DR Pharos; A6NCS4; Tbio.
DR PRO; PR:A6NCS4; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; A6NCS4; protein.
DR Bgee; ENSG00000180053; Expressed in right atrium auricular region and 7 other tissues.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:HGNC-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0055014; P:atrial cardiac muscle cell development; ISS:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; ISS:BHF-UCL.
DR GO; GO:0048565; P:digestive tract development; ISS:BHF-UCL.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:HGNC-UCL.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0021854; P:hypothalamus development; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060039; P:pericardium development; ISS:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:HGNC-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043586; P:tongue development; ISS:BHF-UCL.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; ISS: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 1: Evidence at protein level;
KW Activator; Developmental protein; Disease variant; DNA-binding; Homeobox;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..301
FT /note="Homeobox protein Nkx-2.6"
FT /id="PRO_0000300262"
FT DNA_BIND 132..191
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 22..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 151
FT /note="F -> L (in CTHM; impairs transcriptional activation;
FT dbSNP:rs267606914)"
FT /evidence="ECO:0000269|PubMed:15649947"
FT /id="VAR_063278"
FT VARIANT 152
FT /note="K -> Q (in CTHM)"
FT /evidence="ECO:0000269|PubMed:25380965"
FT /id="VAR_073164"
FT VARIANT 176
FT /note="V -> A (in CTHM)"
FT /evidence="ECO:0000269|PubMed:25195019"
FT /id="VAR_073165"
FT CONFLICT 199
FT /note="A -> G (in Ref. 2; CN272646)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 301 AA; 32121 MW; BA3FECFC7F1804EA CRC64;
MLLSPVTSTP FSVKDILRLE RERSCPAASP HPRVRKSPEN FQYLRMDAEP RGSEVHNAGG
GGGDRKLDGS EPPGGPCEAV LEMDAERMGE PQPGLNAASP LGGGTRVPER GVGNSGDSVR
GGRSEQPKAR QRRKPRVLFS QAQVLALERR FKQQRYLSAP EREHLASALQ LTSTQVKIWF
QNRRYKCKRQ RQDKSLELAG HPLTPRRVAV PVLVRDGKPC LGPGPGAPAF PSPYSAAVSP
YSCYGGYSGA PYGAGYGTCY AGAPSGPAPH TPLASAGFGH GGQNATPQGH LAATLQGVRA
W
