NKX61_MESAU
ID NKX61_MESAU Reviewed; 364 AA.
AC Q60554;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 106.
DE RecName: Full=Homeobox protein Nkx-6.1;
DE AltName: Full=Homeobox protein NK-6 homolog A;
GN Name=NKX6-1; Synonyms=NKX6A;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreatic islet;
RX PubMed=7991607; DOI=10.1073/pnas.91.25.12203;
RA Rudnick A., Ling T.Y., Odagiri H., Rutter W.J., German M.S.;
RT "Pancreatic beta cells express a diverse set of homeobox genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12203-12207(1994).
RN [2]
RP DNA-BINDING, AND FUNCTION.
RX PubMed=10799563; DOI=10.1074/jbc.275.19.14743;
RA Mirmira R.G., Watada H., German M.S.;
RT "Beta-cell differentiation factor Nkx6.1 contains distinct DNA binding
RT interference and transcriptional repression domains.";
RL J. Biol. Chem. 275:14743-14751(2000).
RN [3]
RP DNA-BINDING, AND FUNCTION.
RX PubMed=15056733; DOI=10.1210/me.2004-0006;
RA Iype T., Taylor D.G., Ziesmann S.M., Garmey J.C., Watada H., Mirmira R.G.;
RT "The transcriptional repressor Nkx6.1 also functions as a deoxyribonucleic
RT acid context-dependent transcriptional activator during pancreatic beta-
RT cell differentiation: evidence for feedback activation of the nkx6.1 gene
RT by Nkx6.1.";
RL Mol. Endocrinol. 18:1363-1375(2004).
RN [4]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF 321-GLU--ASP-324.
RX PubMed=16101311; DOI=10.1021/bi050821m;
RA Taylor D.G., Babu D., Mirmira R.G.;
RT "The C-terminal domain of the beta cell homeodomain factor Nkx6.1 enhances
RT sequence-selective DNA binding at the insulin promoter.";
RL Biochemistry 44:11269-11278(2005).
RN [5]
RP FUNCTION IN TRANSCRIPTIONAL REGULATION IN ISLET BETA CELLS.
RX PubMed=18347054; DOI=10.1128/mcb.01791-07;
RA Schisler J.C., Fueger P.T., Babu D.A., Hohmeier H.E., Tessem J.S., Lu D.,
RA Becker T.C., Naziruddin B., Levy M., Mirmira R.G., Newgard C.B.;
RT "Stimulation of human and rat islet beta-cell proliferation with retention
RT of function by the homeodomain transcription factor Nkx6.1.";
RL Mol. Cell. Biol. 28:3465-3476(2008).
CC -!- FUNCTION: Together with NKX2-2 and IRX3 acts to restrict the generation
CC of motor neurons to the appropriate region of the neural tube. Belongs
CC to the class II proteins of neuronal progenitor factors, which are
CC induced by SHH signals (By similarity). Transcription factor which
CC binds to specific A/T-rich DNA sequences in the promoter regions of a
CC number of genes. Involved in transcriptional regulation in islet beta
CC cells. Binds to the insulin promoter and is involved in regulation of
CC the insulin gene. {ECO:0000250, ECO:0000269|PubMed:10799563,
CC ECO:0000269|PubMed:15056733, ECO:0000269|PubMed:16101311,
CC ECO:0000269|PubMed:18347054}.
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; X81409; CAA57166.1; -; mRNA.
DR PIR; I48188; I48188.
DR RefSeq; NP_001268625.1; NM_001281696.1.
DR AlphaFoldDB; Q60554; -.
DR SMR; Q60554; -.
DR STRING; 10036.XP_005076419.1; -.
DR GeneID; 101826537; -.
DR CTD; 4825; -.
DR eggNOG; KOG0847; Eukaryota.
DR OrthoDB; 1263401at2759; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0051594; P:detection of glucose; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; IEA:InterPro.
DR GO; GO:0031016; P:pancreas development; IMP:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; IMP:BHF-UCL.
DR GO; GO:0030516; P:regulation of axon extension; IEA:InterPro.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:InterPro.
DR GO; GO:0072560; P:type B pancreatic cell maturation; IMP: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..364
FT /note="Homeobox protein Nkx-6.1"
FT /id="PRO_0000048952"
FT DNA_BIND 236..295
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 35..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..268
FT /note="Repressor domain"
FT REGION 294..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..364
FT /note="Involved in DNA-binding"
FT COMPBIAS 49..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..134
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:0000250|UniProtKB:P78426"
FT MUTAGEN 321..324
FT /note="EEDD->RPPR: Loss of DNA -binding specificity."
FT /evidence="ECO:0000269|PubMed:16101311"
SQ SEQUENCE 364 AA; 37646 MW; 08B1AE1225F0F06E CRC64;
MLAVGAMEGP RQSAFLLSSP PLAALHSMAE MKTPLYPATY PPLPTGPPSS SSSSSSSSPS
PPLGAHNPGG LKPPAAGGLS SLSSPPQQLS AATPHGINDI LSRPSMPVAS GAALPSASPS
GSSSSSSSSA SATSASAAAA AAAAAAAAAA SSPAGLLAGL PRFSSLSPPP PPPGLYFSPS
AAAVAAVGRY PKPLAELPGR APIFWPGVMQ SPPWRDARLA CTPHQGSILL DKDGKRKHTR
PTFSGQQIFA LEKTFEQTKY LAGPERARLA YSLGMTESQV KVWFQNRRTK WRKKHAAEMA
TAKKKQDSET ERLKGTSENE EEDDDYNKPL DPNSDDEKIT QLLKKHKSSS GGLLLHASEA
EGSS