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Q99MA9

- NKX61_MOUSE

UniProt

Q99MA9 - NKX61_MOUSE

Protein

Homeobox protein Nkx-6.1

Gene

Nkx6-1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Involved in transcriptional regulation in islet beta cells. Binds to the insulin promoter and is involved in regulation of the insulin gene. Together with NKX2-2 and IRX3 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi237 – 29660HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: Ensembl
    2. sequence-specific DNA binding transcription factor activity Source: MGI
    3. transcription regulatory region sequence-specific DNA binding Source: InterPro

    GO - Biological processi

    1. cell differentiation Source: MGI
    2. cell proliferation Source: Ensembl
    3. cellular response to cytokine stimulus Source: Ensembl
    4. cellular response to peptide hormone stimulus Source: Ensembl
    5. central nervous system neuron differentiation Source: MGI
    6. endocrine pancreas development Source: MGI
    7. negative regulation of glial cell differentiation Source: MGI
    8. oligodendrocyte differentiation Source: MGI
    9. positive regulation of glial cell differentiation Source: MGI
    10. positive regulation of insulin secretion Source: Ensembl
    11. positive regulation of neuron differentiation Source: MGI
    12. regulation of axon extension Source: MGI
    13. regulation of neuron migration Source: MGI
    14. regulation of transcription from RNA polymerase II promoter Source: MGI
    15. regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification Source: MGI
    16. regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification Source: MGI
    17. response to drug Source: Ensembl
    18. response to nicotine Source: Ensembl
    19. smoothened signaling pathway Source: MGI
    20. transcription from RNA polymerase II promoter Source: Ensembl
    21. type B pancreatic cell development Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_208465. Regulation of gene expression in early pancreatic precursor cells.
    REACT_214529. Regulation of gene expression in beta cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homeobox protein Nkx-6.1
    Alternative name(s):
    Homeobox protein NK-6 homolog A
    Gene namesi
    Name:Nkx6-1
    Synonyms:Nkx6.1, Nkx6a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:1206039. Nkx6-1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Dramatically diminished numbers of beta cells within the pancreatic islets and secretion of insulin at only 2% of normal levels. Loss of expression of Mafa, which is involved in insulin gene transcription.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 365365Homeobox protein Nkx-6.1PRO_0000048953Add
    BLAST

    Proteomic databases

    PRIDEiQ99MA9.

    PTM databases

    PhosphoSiteiQ99MA9.

    Expressioni

    Tissue specificityi

    Expressed by neuronal progenitor cells in discrete domains of the ventral neural tube.1 Publication

    Gene expression databases

    BgeeiQ99MA9.
    GenevestigatoriQ99MA9.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000042716.

    Structurei

    3D structure databases

    ProteinModelPortaliQ99MA9.
    SMRiQ99MA9. Positions 244-294.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni102 – 269168Repressor domainBy similarityAdd
    BLAST
    Regioni307 – 36559Involved in DNA-bindingBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi49 – 6113Poly-SerAdd
    BLAST
    Compositional biasi119 – 13214Poly-SerAdd
    BLAST
    Compositional biasi136 – 15116Poly-AlaAdd
    BLAST
    Compositional biasi169 – 1746Poly-Pro
    Compositional biasi323 – 3264Poly-Asp

    Domaini

    The C-terminal domain contributes to sequence-specific DNA-binding.

    Sequence similaritiesi

    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG265304.
    GeneTreeiENSGT00750000117350.
    HOGENOMiHOG000060127.
    HOVERGENiHBG070987.
    InParanoidiB2RQP4.
    KOiK08030.
    OMAiTPLYPAY.
    OrthoDBiEOG7Z95QB.
    PhylomeDBiQ99MA9.
    TreeFamiTF327063.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    IPR000047. HTH_motif.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    [Graphical view]
    PRINTSiPR00024. HOMEOBOX.
    PR00031. HTHREPRESSR.
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q99MA9-1 [UniParc]FASTAAdd to Basket

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    MLAVGAMEGP RQSAFLLSSP PLAALHSMAE MKTPLYPAAY PPLPTGPPSS    50
    SSSSSSSSSP SPPLGSHNPG GLKPPAAGGL SSLGSPPQQL SAATPHGIND 100
    ILSRPSMPVA SGAALPSASP SGSSSSSSSS ASATSASAAA AAAAAAAAAA 150
    ASSPAGLLAG LPRFSSLSPP PPPPGLYFSP SAAAVAAVGR YPKPLAELPG 200
    RTPIFWPGVM QSPPWRDARL ACTPHQGSIL LDKDGKRKHT RPTFSGQQIF 250
    ALEKTFEQTK YLAGPERARL AYSLGMTESQ VKVWFQNRRT KWRKKHAAEM 300
    ATAKKKQDSE TERLKGTSEN EEDDDDYNKP LDPNSDDEKI TQLLKKHKSS 350
    GGSLLLHASE AEGSS 365
    Length:365
    Mass (Da):37,705
    Last modified:June 1, 2001 - v1
    Checksum:iB6AABAF5748A99E8
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF357883 mRNA. Translation: AAK37567.1.
    BC138019 mRNA. Translation: AAI38020.1.
    BC138020 mRNA. Translation: AAI38021.1.
    AF291666 Genomic DNA. Translation: AAG30415.1.
    CCDSiCCDS19471.1.
    RefSeqiNP_659204.1. NM_144955.2.
    UniGeneiMm.193072.

    Genome annotation databases

    EnsembliENSMUST00000044125; ENSMUSP00000042716; ENSMUSG00000035187.
    GeneIDi18096.
    KEGGimmu:18096.
    UCSCiuc008yim.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF357883 mRNA. Translation: AAK37567.1 .
    BC138019 mRNA. Translation: AAI38020.1 .
    BC138020 mRNA. Translation: AAI38021.1 .
    AF291666 Genomic DNA. Translation: AAG30415.1 .
    CCDSi CCDS19471.1.
    RefSeqi NP_659204.1. NM_144955.2.
    UniGenei Mm.193072.

    3D structure databases

    ProteinModelPortali Q99MA9.
    SMRi Q99MA9. Positions 244-294.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000042716.

    PTM databases

    PhosphoSitei Q99MA9.

    Proteomic databases

    PRIDEi Q99MA9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000044125 ; ENSMUSP00000042716 ; ENSMUSG00000035187 .
    GeneIDi 18096.
    KEGGi mmu:18096.
    UCSCi uc008yim.1. mouse.

    Organism-specific databases

    CTDi 4825.
    MGIi MGI:1206039. Nkx6-1.

    Phylogenomic databases

    eggNOGi NOG265304.
    GeneTreei ENSGT00750000117350.
    HOGENOMi HOG000060127.
    HOVERGENi HBG070987.
    InParanoidi B2RQP4.
    KOi K08030.
    OMAi TPLYPAY.
    OrthoDBi EOG7Z95QB.
    PhylomeDBi Q99MA9.
    TreeFami TF327063.

    Enzyme and pathway databases

    Reactomei REACT_208465. Regulation of gene expression in early pancreatic precursor cells.
    REACT_214529. Regulation of gene expression in beta cells.

    Miscellaneous databases

    NextBioi 293251.
    PROi Q99MA9.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q99MA9.
    Genevestigatori Q99MA9.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    IPR000047. HTH_motif.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    [Graphical view ]
    PRINTSi PR00024. HOMEOBOX.
    PR00031. HTHREPRESSR.
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of partial cDNA sequence for the mouse homeodomain protein, Nkx6.1."
      Sander M., Nelson S.B.
      Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6 X DBA/2.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. "Transcriptional and translational regulation of beta-cell differentiation factor Nkx6.1."
      Watada H., Mirmira R.G., Leung J., German M.S.
      J. Biol. Chem. 275:34224-34230(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-224.
      Strain: 129/Sv.
    4. "Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas."
      Sander M., Sussel L., Conners J., Scheel D., Kalamaras J., Dela Cruz F., Schwitzgebel V., Hayes-Jordan A., German M.
      Development 127:5533-5540(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    5. "A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube."
      Briscoe J., Pierani A., Jessell T.M., Ericson J.
      Cell 101:435-445(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NEURAL PATTERNING, TISSUE SPECIFICITY.
    6. "The MafA transcription factor appears to be responsible for tissue-specific expression of insulin."
      Matsuoka T.A., Artner I., Henderson E., Means A., Sander M., Stein R.
      Proc. Natl. Acad. Sci. U.S.A. 101:2930-2933(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiNKX61_MOUSE
    AccessioniPrimary (citable) accession number: Q99MA9
    Secondary accession number(s): B2RQP4, Q9ERQ7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 10, 2003
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 100 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3