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Q01101

- INSM1_HUMAN

UniProt

Q01101 - INSM1_HUMAN

Protein

Insulinoma-associated protein 1

Gene

INSM1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.5 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri267 – 28721C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri295 – 31723C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri367 – 38923C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri441 – 46424C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri469 – 49224C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin DNA binding Source: UniProtKB
    2. core promoter binding Source: UniProtKB
    3. cyclin binding Source: UniProtKB
    4. histone deacetylase binding Source: UniProtKB
    5. metal ion binding Source: UniProtKB-KW
    6. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. adrenal chromaffin cell differentiation Source: UniProtKB
    2. cell cycle Source: UniProtKB-KW
    3. endocrine pancreas development Source: Reactome
    4. negative regulation of cell proliferation Source: UniProtKB
    5. negative regulation of protein phosphorylation Source: UniProtKB
    6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    7. noradrenergic neuron development Source: UniProtKB
    8. norepinephrine biosynthetic process Source: UniProtKB
    9. pancreatic A cell differentiation Source: UniProtKB
    10. positive regulation of cell cycle arrest Source: UniProtKB
    11. positive regulation of cell differentiation Source: UniProtKB
    12. positive regulation of neural precursor cell proliferation Source: UniProtKB
    13. regulation of gene expression Source: UniProtKB
    14. regulation of protein complex assembly Source: UniProtKB
    15. sympathetic ganglion development Source: UniProtKB
    16. transcription, DNA-templated Source: UniProtKB-KW
    17. transdifferentiation Source: UniProtKB
    18. type B pancreatic cell development Source: Ensembl
    19. type B pancreatic cell differentiation Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein, Repressor

    Keywords - Biological processi

    Cell cycle, Differentiation, Neurogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_13650. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.
    SignaLinkiQ01101.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulinoma-associated protein 1
    Alternative name(s):
    Zinc finger protein IA-1
    Gene namesi
    Name:INSM1
    Synonyms:IA1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:6090. INSM1.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. nucleoplasm Source: Reactome
    2. nucleus Source: UniProtKB
    3. transcriptional repressor complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi43 – 5816PPAPS…PPPPP → LLALSLVLGLLLLLLL: Inhibits weakly translational repression activity. Inhibits interaction with CCND1 and cell cycle arrest. 1 PublicationAdd
    BLAST

    Organism-specific databases

    PharmGKBiPA29897.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 510510Insulinoma-associated protein 1PRO_0000047268Add
    BLAST

    Proteomic databases

    PaxDbiQ01101.
    PRIDEiQ01101.

    PTM databases

    PhosphoSiteiQ01101.

    Expressioni

    Tissue specificityi

    Expressed in pancreatic duct cells. Expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, medulloblastoma, retinoblastoma, pheochromacytoma, medullary thyroid carcinoma and small cell lung carcinoma.2 Publications

    Inductioni

    Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3.2 Publications

    Gene expression databases

    BgeeiQ01101.
    CleanExiHS_INSM1.
    GenevestigatoriQ01101.

    Interactioni

    Subunit structurei

    Interacts (via the SNAG domain) with HDAC1. Interacts (via the SNAG domain) with HDAC2. Interacts (via the SNAG domain) with KDM1A. Interacts (via the SNAG domain) with RCOR1. Interacts with SORBS1 By similarity. Interacts (via the N-terminal region) with CCND1 (via cyclin N-terminal domain); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and increases its transcriptional repressor activity. Interacts with HDAC3; the interaction increases its transcriptional repressor activity. Interacts with HDAC1.By similarity4 Publications

    Protein-protein interaction databases

    BioGridi109853. 5 interactions.
    IntActiQ01101. 5 interactions.
    MINTiMINT-1395936.
    STRINGi9606.ENSP00000312631.

    Structurei

    Secondary structure

    1
    510
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 53
    Beta strandi449 – 4524
    Helixi453 – 4619
    Beta strandi466 – 4705
    Beta strandi477 – 4804
    Helixi481 – 4899

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2LV2NMR-A424-497[»]
    3ZMSX-ray2.96C2-510[»]
    ProteinModelPortaliQ01101.
    SMRiQ01101. Positions 234-320, 359-395, 424-497.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 2020SNAG domainBy similarityAdd
    BLAST
    Regioni43 – 5816Necessary for interaction with CCND1Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1 – 250250Ala/Gly/Pro-richAdd
    BLAST

    Domaini

    The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.

    Sequence similaritiesi

    Belongs to the INSM1 family.Curated
    Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri267 – 28721C2H2-type 1; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri295 – 31723C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri367 – 38923C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri441 – 46424C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri469 – 49224C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG308747.
    HOGENOMiHOG000113079.
    HOVERGENiHBG052137.
    InParanoidiQ01101.
    OMAiREHEKHK.
    OrthoDBiEOG7JMGDD.
    PhylomeDBiQ01101.
    TreeFamiTF320538.

    Family and domain databases

    Gene3Di3.30.160.60. 1 hit.
    InterProiIPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF00096. zf-C2H2. 4 hits.
    [Graphical view]
    SMARTiSM00355. ZnF_C2H2. 5 hits.
    [Graphical view]
    PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q01101-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPRGFLVKRS KKSTPVSYRV RGGEDGDRAL LLSPSCGGAR AEPPAPSPVP    50
    GPLPPPPPAE RAHAALAAAL ACAPGPQPPP QGPRAAHFGN PEAAHPAPLY 100
    SPTRPVSREH EKHKYFERSF NLGSPVSAES FPTPAALLGG GGGGGASGAG 150
    GGGTCGGDPL LFAPAELKMG TAFSAGAEAA RGPGPGPPLP PAAALRPPGK 200
    RPPPPTAAEP PAKAVKAPGA KKPKAIRKLH FEDEVTTSPV LGLKIKEGPV 250
    EAPRGRAGGA ARPLGEFICQ LCKEEYADPF ALAQHKCSRI VRVEYRCPEC 300
    AKVFSCPANL ASHRRWHKPR PAPAAARAPE PEAAARAEAR EAPGGGSDRD 350
    TPSPGGVSES GSEDGLYECH HCAKKFRRQA YLRKHLLAHH QALQAKGAPL 400
    APPAEDLLAL YPGPDEKAPQ EAAGDGEGAG VLGLSASAEC HLCPVCGESF 450
    ASKGAQERHL RLLHAAQVFP CKYCPATFYS SPGLTRHINK CHPSENRQVI 500
    LLQVPVRPAC 510
    Length:510
    Mass (Da):52,923
    Last modified:June 1, 1994 - v1
    Checksum:i22D4E97696397365
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93119 mRNA. Translation: AAA58680.1.
    AL161658 Genomic DNA. Translation: CAC36065.1.
    U07172 Genomic DNA. Translation: AAA20938.1.
    CCDSiCCDS13143.1.
    PIRiA42750.
    RefSeqiNP_002187.1. NM_002196.2.
    UniGeneiHs.89584.

    Genome annotation databases

    EnsembliENST00000310227; ENSP00000312631; ENSG00000173404.
    GeneIDi3642.
    KEGGihsa:3642.
    UCSCiuc002wrx.3. human.

    Polymorphism databases

    DMDMi547700.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93119 mRNA. Translation: AAA58680.1 .
    AL161658 Genomic DNA. Translation: CAC36065.1 .
    U07172 Genomic DNA. Translation: AAA20938.1 .
    CCDSi CCDS13143.1.
    PIRi A42750.
    RefSeqi NP_002187.1. NM_002196.2.
    UniGenei Hs.89584.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2LV2 NMR - A 424-497 [» ]
    3ZMS X-ray 2.96 C 2-510 [» ]
    ProteinModelPortali Q01101.
    SMRi Q01101. Positions 234-320, 359-395, 424-497.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109853. 5 interactions.
    IntActi Q01101. 5 interactions.
    MINTi MINT-1395936.
    STRINGi 9606.ENSP00000312631.

    PTM databases

    PhosphoSitei Q01101.

    Polymorphism databases

    DMDMi 547700.

    Proteomic databases

    PaxDbi Q01101.
    PRIDEi Q01101.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000310227 ; ENSP00000312631 ; ENSG00000173404 .
    GeneIDi 3642.
    KEGGi hsa:3642.
    UCSCi uc002wrx.3. human.

    Organism-specific databases

    CTDi 3642.
    GeneCardsi GC20P020348.
    HGNCi HGNC:6090. INSM1.
    MIMi 600010. gene.
    neXtProti NX_Q01101.
    PharmGKBi PA29897.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG308747.
    HOGENOMi HOG000113079.
    HOVERGENi HBG052137.
    InParanoidi Q01101.
    OMAi REHEKHK.
    OrthoDBi EOG7JMGDD.
    PhylomeDBi Q01101.
    TreeFami TF320538.

    Enzyme and pathway databases

    Reactomei REACT_13650. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.
    SignaLinki Q01101.

    Miscellaneous databases

    GeneWikii INSM1.
    GenomeRNAii 3642.
    NextBioi 14255.
    PROi Q01101.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q01101.
    CleanExi HS_INSM1.
    Genevestigatori Q01101.

    Family and domain databases

    Gene3Di 3.30.160.60. 1 hit.
    InterProi IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF00096. zf-C2H2. 4 hits.
    [Graphical view ]
    SMARTi SM00355. ZnF_C2H2. 5 hits.
    [Graphical view ]
    PROSITEi PS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel human insulinoma-associated cDNA, IA-1, encodes a protein with 'zinc-finger' DNA-binding motifs."
      Goto Y., de Silva M.G., Toscani A., Prabhakar B.S., Notkins A.L., Lan M.S.
      J. Biol. Chem. 267:15252-15257(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    2. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1."
      Lan M.S., Li Q., Lu J., Modi W.S., Notkins A.L.
      J. Biol. Chem. 269:14170-14174(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
    4. "Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence."
      Breslin M.B., Zhu M., Notkins A.L., Lan M.S.
      Nucleic Acids Res. 30:1038-1045(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING.
    5. "NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system."
      Breslin M.B., Zhu M., Lan M.S.
      J. Biol. Chem. 278:38991-38997(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, TISSUE SPECIFICITY.
    6. "INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases."
      Liu W.D., Wang H.W., Muguira M., Breslin M.B., Lan M.S.
      Biochem. J. 397:169-177(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1; HDAC1 AND HDAC3.
    7. Cited for: FUNCTION, INDUCTION.
    8. "Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription."
      Wang H.W., Muguira M., Liu W.D., Zhang T., Chen C., Aucoin R., Breslin M.B., Lan M.S.
      J. Endocrinol. 198:29-39(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1 AND HDAC3.
    9. "Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest."
      Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.
      J. Biol. Chem. 284:5574-5581(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1, MUTAGENESIS OF 43-PRO--PRO-58.
    10. "Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation."
      Lan M.S., Breslin M.B.
      FASEB J. 23:2024-2033(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    11. "Solution NMR structure of C2H2-type zinc-fingers 4 and 5 from human insulinoma-associated protein 1 (fragment 424-497), Northeast structural genomics consortium target HR7614B (Casp target)."
      Northeast structural genomics consortium (NESG)
      Submitted (OCT-2012) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 424-497 IN COMPLEX WITH ZINC IONS.

    Entry informationi

    Entry nameiINSM1_HUMAN
    AccessioniPrimary (citable) accession number: Q01101
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3