NKX61_HUMAN
ID NKX61_HUMAN Reviewed; 367 AA.
AC P78426;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Homeobox protein Nkx-6.1;
DE AltName: Full=Homeobox protein NK-6 homolog A;
GN Name=NKX6-1; Synonyms=NKX6A;
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].
RC TISSUE=Pancreatic islet;
RX PubMed=9119408; DOI=10.1006/geno.1996.4568;
RA Inoue H., Rudnick A., German M.S., Veile R., Donis-Keller H., Permutt M.A.;
RT "Isolation, characterization, and chromosomal mapping of the human Nkx6.1
RT gene (NKX6A), a new pancreatic islet homeobox gene.";
RL Genomics 40:367-370(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-189, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Transcription factor which binds to specific A/T-rich DNA
CC sequences in the promoter regions of a number of genes. Involved in the
CC development of insulin-producing beta cells in the islets of Langerhans
CC at the secondary transition (By similarity). Together with NKX2-2 and
CC IRX3 acts to restrict the generation of motor neurons to the
CC appropriate region of the neural tube. Belongs to the class II proteins
CC of neuronal progenitor factors, which are induced by SHH signals (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q99MA9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Pancreatic beta cells.
CC -!- DOMAIN: The C-terminal domain contributes to sequence-specific DNA-
CC binding. {ECO:0000250}.
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DR EMBL; U66799; AAD11962.1; -; Genomic_DNA.
DR EMBL; U66797; AAD11962.1; JOINED; Genomic_DNA.
DR EMBL; U66798; AAD11962.1; JOINED; Genomic_DNA.
DR EMBL; AC096766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS3607.1; -.
DR RefSeq; NP_006159.2; NM_006168.2.
DR AlphaFoldDB; P78426; -.
DR SMR; P78426; -.
DR BioGRID; 110889; 3.
DR IntAct; P78426; 1.
DR MINT; P78426; -.
DR STRING; 9606.ENSP00000295886; -.
DR iPTMnet; P78426; -.
DR PhosphoSitePlus; P78426; -.
DR BioMuta; NKX6-1; -.
DR DMDM; 288558819; -.
DR EPD; P78426; -.
DR jPOST; P78426; -.
DR MassIVE; P78426; -.
DR PaxDb; P78426; -.
DR PeptideAtlas; P78426; -.
DR PRIDE; P78426; -.
DR ProteomicsDB; 57625; -.
DR Antibodypedia; 25238; 345 antibodies from 32 providers.
DR DNASU; 4825; -.
DR Ensembl; ENST00000295886.5; ENSP00000295886.3; ENSG00000163623.10.
DR GeneID; 4825; -.
DR KEGG; hsa:4825; -.
DR MANE-Select; ENST00000295886.5; ENSP00000295886.3; NM_006168.3; NP_006159.2.
DR UCSC; uc003hpa.2; human.
DR CTD; 4825; -.
DR DisGeNET; 4825; -.
DR GeneCards; NKX6-1; -.
DR HGNC; HGNC:7839; NKX6-1.
DR HPA; ENSG00000163623; Tissue enhanced (brain, esophagus, pancreas).
DR MIM; 602563; gene.
DR neXtProt; NX_P78426; -.
DR OpenTargets; ENSG00000163623; -.
DR PharmGKB; PA31646; -.
DR VEuPathDB; HostDB:ENSG00000163623; -.
DR eggNOG; KOG0847; Eukaryota.
DR GeneTree; ENSGT00940000160897; -.
DR HOGENOM; CLU_064820_0_0_1; -.
DR InParanoid; P78426; -.
DR OMA; ALYWPAN; -.
DR OrthoDB; 1263401at2759; -.
DR PhylomeDB; P78426; -.
DR TreeFam; TF327063; -.
DR PathwayCommons; P78426; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR Reactome; R-HSA-210747; Regulation of gene expression in early pancreatic precursor cells.
DR SignaLink; P78426; -.
DR SIGNOR; P78426; -.
DR BioGRID-ORCS; 4825; 16 hits in 1089 CRISPR screens.
DR GeneWiki; NKX6-1; -.
DR GenomeRNAi; 4825; -.
DR Pharos; P78426; Tbio.
DR PRO; PR:P78426; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P78426; protein.
DR Bgee; ENSG00000163623; Expressed in lower esophagus muscularis layer and 56 other tissues.
DR ExpressionAtlas; P78426; baseline and differential.
DR Genevisible; P78426; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEA:Ensembl.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IEA:Ensembl.
DR GO; GO:0051594; P:detection of glucose; ISS:BHF-UCL.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; IEA:InterPro.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0031016; P:pancreas development; ISS:BHF-UCL.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0032024; P:positive regulation of insulin secretion; 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:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; ISS:BHF-UCL.
DR GO; GO:0030516; P:regulation of axon extension; IEA:Ensembl.
DR GO; GO:2001222; P:regulation of neuron migration; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0072560; P:type B pancreatic cell maturation; ISS:BHF-UCL.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
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 InterPro; IPR000047; HTH_motif.
DR InterPro; IPR033630; NKX-6.1.
DR PANTHER; PTHR24340:SF31; PTHR24340:SF31; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
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; DNA-binding; Homeobox; Methylation;
KW Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..367
FT /note="Homeobox protein Nkx-6.1"
FT /id="PRO_0000048951"
FT DNA_BIND 236..295
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 36..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 102..268
FT /note="Repressor domain"
FT /evidence="ECO:0000250"
FT REGION 294..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..367
FT /note="Involved in DNA-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 49..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..321
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 189
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CONFLICT 100
FT /note="D -> N (in Ref. 1; AAD11962)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 367 AA; 37849 MW; 5C78F06C3CAE6486 CRC64;
MLAVGAMEGT RQSAFLLSSP PLAALHSMAE MKTPLYPAAY PPLPAGPPSS SSSSSSSSSP
SPPLGTHNPG GLKPPATGGL SSLGSPPQQL SAATPHGIND ILSRPSMPVA SGAALPSASP
SGSSSSSSSS ASASSASAAA AAAAAAAAAA SSPAGLLAGL PRFSSLSPPP PPPGLYFSPS
AAAVAAVGRY PKPLAELPGR TPIFWPGVMQ SPPWRDARLA CTPHQGSILL DKDGKRKHTR
PTFSGQQIFA LEKTFEQTKY LAGPERARLA YSLGMTESQV KVWFQNRRTK WRKKHAAEMA
TAKKKQDSET ERLKGASENE EEDDDYNKPL DPNSDDEKIT QLLKKHKSSS GGGGGLLLHA
SEPESSS
