NKX61_MOUSE
ID NKX61_MOUSE Reviewed; 365 AA.
AC Q99MA9; B2RQP4; Q9ERQ7;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Homeobox protein Nkx-6.1;
DE AltName: Full=Homeobox protein NK-6 homolog A;
GN Name=Nkx6-1; Synonyms=Nkx6.1, Nkx6a;
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].
RC STRAIN=C57BL/6 X DBA/2;
RA Sander M., Nelson S.B.;
RT "Isolation of partial cDNA sequence for the mouse homeodomain protein,
RT Nkx6.1.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-224.
RC STRAIN=129/Sv;
RX PubMed=10938085; DOI=10.1074/jbc.m004981200;
RA Watada H., Mirmira R.G., Leung J., German M.S.;
RT "Transcriptional and translational regulation of beta-cell differentiation
RT factor Nkx6.1.";
RL J. Biol. Chem. 275:34224-34230(2000).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=11076772; DOI=10.1242/dev.127.24.5533;
RA Sander M., Sussel L., Conners J., Scheel D., Kalamaras J., Dela Cruz F.,
RA Schwitzgebel V., Hayes-Jordan A., German M.;
RT "Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of
RT beta-cell formation in the pancreas.";
RL Development 127:5533-5540(2000).
RN [5]
RP FUNCTION IN NEURAL PATTERNING, AND TISSUE SPECIFICITY.
RX PubMed=10830170; DOI=10.1016/s0092-8674(00)80853-3;
RA Briscoe J., Pierani A., Jessell T.M., Ericson J.;
RT "A homeodomain protein code specifies progenitor cell identity and neuronal
RT fate in the ventral neural tube.";
RL Cell 101:435-445(2000).
CC -!- FUNCTION: Transcription factor which binds to specific A/T-rich DNA
CC sequences in the promoter regions of a number of genes. Required for
CC the development of insulin-producing beta cells in the islets of
CC Langerhans at the secondary transition (PubMed:11076772). Involved in
CC transcriptional regulation of the insulin gene. Together with NKX2-2
CC and IRX3, restricts the generation of motor neurons to the appropriate
CC region of the neural tube. Belongs to the class II proteins of neuronal
CC progenitor factors, which are induced by SHH signals.
CC {ECO:0000269|PubMed:10830170, ECO:0000269|PubMed:11076772}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11076772}.
CC -!- TISSUE SPECIFICITY: Expressed by neuronal progenitor cells in discrete
CC domains of the ventral neural tube (PubMed:10830170). In the pancreas,
CC expressed exclusively in insulin-producing beta cells of the islets of
CC Langerhans (at protein level) (PubMed:11076772).
CC {ECO:0000269|PubMed:10830170, ECO:0000269|PubMed:11076772}.
CC -!- DEVELOPMENTAL STAGE: In the developing pancreas, detected as early as
CC 10.5 dpc in the majority of epithelial cells. This broad expression
CC pattern persists through 12.5 dpc. Around 13.5 dpc, with the start of
CC the secondary transition, becomes restricted and by 15.5 dpc,
CC exclusively detected in insulin-expressing beta cells and in some
CC scattered ductal and periductal cells (at protein level).
CC {ECO:0000269|PubMed:11076772}.
CC -!- DOMAIN: The C-terminal domain contributes to sequence-specific DNA-
CC binding.
CC -!- DISRUPTION PHENOTYPE: Embryonic development of mutant mice is normal
CC until 13.5 dpc. At this stage, the normal expansion of pancreatic beta
CC cells does not occur. At 18.5 dpc, the numbers of beta cells is
CC dramatically decreased and the pancreatic insulin content is only 2% of
CC wild-type. No effect on the production of other pancreatic hormones,
CC including glucagon, somatostatin and pancreatic polypeptide (PP)
CC (PubMed:11076772). Simultaneous knockout of NKX6-1 and NKX2-2 results
CC in the complete absence of insulin-expressing cells in the pancreas
CC throughout development, and instead accumulation of incompletely
CC differentiated beta cells, a phenotype not distinguable from the single
CC NKX2-2 knockout (PubMed:11076772). {ECO:0000269|PubMed:11076772}.
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DR EMBL; AF357883; AAK37567.1; -; mRNA.
DR EMBL; BC138019; AAI38020.1; -; mRNA.
DR EMBL; BC138020; AAI38021.1; -; mRNA.
DR EMBL; AF291666; AAG30415.1; -; Genomic_DNA.
DR CCDS; CCDS19471.1; -.
DR RefSeq; NP_659204.1; NM_144955.2.
DR AlphaFoldDB; Q99MA9; -.
DR SMR; Q99MA9; -.
DR STRING; 10090.ENSMUSP00000042716; -.
DR iPTMnet; Q99MA9; -.
DR PhosphoSitePlus; Q99MA9; -.
DR PaxDb; Q99MA9; -.
DR PRIDE; Q99MA9; -.
DR ProteomicsDB; 293855; -.
DR Antibodypedia; 25238; 345 antibodies from 32 providers.
DR DNASU; 18096; -.
DR Ensembl; ENSMUST00000044125; ENSMUSP00000042716; ENSMUSG00000035187.
DR GeneID; 18096; -.
DR KEGG; mmu:18096; -.
DR UCSC; uc008yim.1; mouse.
DR CTD; 4825; -.
DR MGI; MGI:1206039; Nkx6-1.
DR VEuPathDB; HostDB:ENSMUSG00000035187; -.
DR eggNOG; KOG0847; Eukaryota.
DR GeneTree; ENSGT00940000160897; -.
DR HOGENOM; CLU_064820_0_0_1; -.
DR InParanoid; Q99MA9; -.
DR OMA; ALYWPAN; -.
DR OrthoDB; 1263401at2759; -.
DR PhylomeDB; Q99MA9; -.
DR TreeFam; TF327063; -.
DR BioGRID-ORCS; 18096; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q99MA9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q99MA9; protein.
DR Bgee; ENSMUSG00000035187; Expressed in dorsal pancreas and 51 other tissues.
DR Genevisible; Q99MA9; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; 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:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0022008; P:neurogenesis; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0001764; P:neuron migration; IEA:InterPro.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IGI:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IGI:MGI.
DR GO; GO:0030516; P:regulation of axon extension; IMP:MGI.
DR GO; GO:2001222; P:regulation of neuron migration; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
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; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0003323; P:type B pancreatic cell development; IEA:Ensembl.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:MGI.
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 Developmental protein; DNA-binding; Homeobox; Methylation; Nucleus;
KW Reference proteome.
FT CHAIN 1..365
FT /note="Homeobox protein Nkx-6.1"
FT /id="PRO_0000048953"
FT DNA_BIND 237..296
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 35..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 102..269
FT /note="Repressor domain"
FT /evidence="ECO:0000250"
FT REGION 295..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..365
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 82..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..322
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 190
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P78426"
SQ SEQUENCE 365 AA; 37705 MW; B6AABAF5748A99E8 CRC64;
MLAVGAMEGP RQSAFLLSSP PLAALHSMAE MKTPLYPAAY PPLPTGPPSS SSSSSSSSSP
SPPLGSHNPG GLKPPAAGGL SSLGSPPQQL SAATPHGIND ILSRPSMPVA SGAALPSASP
SGSSSSSSSS ASATSASAAA AAAAAAAAAA ASSPAGLLAG LPRFSSLSPP PPPPGLYFSP
SAAAVAAVGR YPKPLAELPG RTPIFWPGVM QSPPWRDARL ACTPHQGSIL LDKDGKRKHT
RPTFSGQQIF ALEKTFEQTK YLAGPERARL AYSLGMTESQ VKVWFQNRRT KWRKKHAAEM
ATAKKKQDSE TERLKGTSEN EEDDDDYNKP LDPNSDDEKI TQLLKKHKSS GGSLLLHASE
AEGSS
