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Q63ZV0 · INSM1_MOUSE

  • Protein
    Insulinoma-associated protein 1
  • Gene
    Insm1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (By similarity).
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

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentnucleus
Cellular Componenttranscription repressor complex
Molecular Functionchromatin DNA binding
Molecular Functioncyclin binding
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription repressor activity, RNA polymerase II-specific
Molecular Functionhistone deacetylase binding
Molecular Functionmetal ion binding
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Biological Processadrenal chromaffin cell differentiation
Biological Processcell migration
Biological Processcell population proliferation
Biological Processendocrine pancreas development
Biological Processendocrine system development
Biological Processnegative regulation of cell population proliferation
Biological Processnegative regulation of protein phosphorylation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnoradrenergic neuron development
Biological Processnorepinephrine biosynthetic process
Biological Processpancreatic A cell differentiation
Biological Processpositive regulation of cell differentiation
Biological Processpositive regulation of cell migration
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of neural precursor cell proliferation
Biological Processregulation of cell cycle
Biological Processregulation of gene expression
Biological Processregulation of protein-containing complex assembly
Biological Processsympathetic ganglion development
Biological Processtransdifferentiation
Biological Processtype B pancreatic cell development
Biological Processtype B pancreatic cell differentiation

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Insulinoma-associated protein 1
  • Alternative names
    • Zinc finger protein IA-1

Gene names

    • Name
      Insm1
    • Synonyms
      Ia1

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q63ZV0
  • Secondary accessions
    • Q9Z113

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Mice die during the second half of gestation; lethality is caused by heart failure due to insufficient catecholamine synthesis. Display pancreatic, intestinal and sympatho-adrenal endocrine cell development impairment. Exhibits fewer terminally dividing neuronogenic basal progenitor cells (BPs) in the neocortex.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 5 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000472691-521Insulinoma-associated protein 1

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in adrenal gland. Expressed in the dentate gyrus of the hippocampus and the wall of the lateral ventricle. Expressed in pancreatic and intestinal endocrine cells.

Developmental stage

Expressed in differentiating endocrine cells of the anterior pituitary gland between 11.5 and 17.5 dpc. Expressed in all hormone-secreting cell types of the pituitary gland. Expressed in primary sympathetic ganglion chain, spinal cord and in neurons of the dorsal root ganglia at 9.5 dpc. Expressed in chromaffin cells of the adrenal medulla at 13.5 dpc (at protein level). Expressed in the developing central nervous system (CNS). Expressed in midbrain-hindbrain region at 9.5 dpc, in the spinal cord and telencephalon at 11 dpc. Expressed in the forebrain, midbrain, hind brain, spinal cord, cerebellum, olfactory bulb and retina between 11.5 and 14.5 dpc. Expressed in neural stem and progenitor cells of the developing neocortex in both the ventricular zone (VZ) and in the adjacent subventricular zone (SVZ), and in the external granule cell layer of the developing cerebellum between 11 and 16.5 dpc. Expressed in neural progenitor cells at the apical side of the VZ, collectively referred to as apical basal cells (APs; neuroepithelial cells, radial glial cells and short neural precursors) between 10.5 and 16.5 dpc. Expressed in neural progenitor cells in the basal region of the VZ between 10.5 and 16.5 dpc and at later stages in basal progenitor cells (BPs) of the SVZ. Expressed in the cerebellum and pineal gland at 18.5 dpc. Expressed in islet progenitor cells at 10.5 dpc. Expressed in endocrine pancreatic cells, enteric nervous system, duodenum, stomach, thymus, thyroid, adrenal glands at 15.5 dpc.

Gene expression databases

Interaction

Subunit

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 (By similarity).
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

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, zinc finger.

Type
IDPosition(s)Description
Region1-20SNAG domain
Region1-59Disordered
Region2-7Required and sufficient for interaction with KDM1A
Compositional bias41-59Pro residues
Region43-56Necessary for interaction with CCND1
Region76-107Disordered
Region180-230Disordered
Compositional bias193-212Pro residues
Zinc finger272-292C2H2-type 1; atypical
Zinc finger300-322C2H2-type 2
Region320-369Disordered
Zinc finger373-395C2H2-type 3
Region398-419Disordered
Compositional bias402-418Pro residues
Zinc finger452-475C2H2-type 4
Zinc finger480-503C2H2-type 5

Domain

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

Sequence similarities

Belongs to the INSM1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    521
  • Mass (Da)
    54,050
  • Last updated
    2004-10-25 v1
  • MD5 Checksum
    21F9EEA0AE33CD417F532491334F9501
MPRGFLVKRSKKSTPVSYRVRGGEDSDRALLLSPGCGGARAEPPVPSPGPLPPPPPPALAERAHAALAAALACAPGPPPPPPPGPRAAHFGNPEAAHPAPLYSPTRPVSREHEKHKYFERSFNLGSPVSAESFPTPAALLAGGGSGANGAGGGGGGTCGGDALLFAPAELKMGTAFSAGAEAARGPGTGPPLSPAAALRPPGKRPAPPAAVATEPPAKAAKAPSAKKPKAIRKLHFEDEVTTSPVLGLKIKEGPVEAPRGRAGGATRPLGEFICQLCKEEYADPFALAQHKCSRIVRVEYRCPECAKVFSCPANLASHRRWHKPRPVPAAARAPEPEAATRAEAREAAGGGSSDRDTPSPGGVSESGSEDGLYECHHCAKKFRRQAYLRKHLLAHHQALQAKGAPPPPPPPPPPAEDILAFYAGPDEKAPQEASGDGEAAGVLGLSATAQCHLCPVCGETFPSKGAQERHLRLLHAAQVFPCKYCPATFYSSPGLTRHINKCHPSENRQVILLQVPVRPAC

Sequence caution

The sequence AAD15718.1 differs from that shown. Reason: Frameshift

Features

Showing features for compositional bias, sequence conflict.

Type
IDPosition(s)Description
Compositional bias41-59Pro residues
Sequence conflict59in Ref. 1; AAD15718
Compositional bias193-212Pro residues
Sequence conflict255in Ref. 1; AAD15718
Sequence conflict266in Ref. 1; AAD15718
Sequence conflict332in Ref. 1
Sequence conflict353in Ref. 1
Sequence conflict371in Ref. 1
Compositional bias402-418Pro residues
Sequence conflict431in Ref. 1; AAD15718
Sequence conflict437in Ref. 1; AAD15718
Sequence conflict446in Ref. 1; AAD15718
Sequence conflict454-456in Ref. 1; AAD15718
Sequence conflict463in Ref. 1; AAD15718

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF044669
EMBL· GenBank· DDBJ
AAD15718.1
EMBL· GenBank· DDBJ
mRNA Frameshift
BC082809
EMBL· GenBank· DDBJ
AAH82809.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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