Q63ZV0 · INSM1_MOUSE
- ProteinInsulinoma-associated protein 1
- GeneInsm1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids521 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameInsulinoma-associated protein 1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ63ZV0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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
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The viewer provides 5 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000047269 | 1-521 | Insulinoma-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
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
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-20 | SNAG domain | |||
Region | 1-59 | Disordered | |||
Region | 2-7 | Required and sufficient for interaction with KDM1A | |||
Compositional bias | 41-59 | Pro residues | |||
Region | 43-56 | Necessary for interaction with CCND1 | |||
Region | 76-107 | Disordered | |||
Region | 180-230 | Disordered | |||
Compositional bias | 193-212 | Pro residues | |||
Zinc finger | 272-292 | C2H2-type 1; atypical | |||
Zinc finger | 300-322 | C2H2-type 2 | |||
Region | 320-369 | Disordered | |||
Zinc finger | 373-395 | C2H2-type 3 | |||
Region | 398-419 | Disordered | |||
Compositional bias | 402-418 | Pro residues | |||
Zinc finger | 452-475 | C2H2-type 4 | |||
Zinc finger | 480-503 | C2H2-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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length521
- Mass (Da)54,050
- Last updated2004-10-25 v1
- MD5 Checksum21F9EEA0AE33CD417F532491334F9501
Sequence caution
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 41-59 | Pro residues | |||
Sequence conflict | 59 | in Ref. 1; AAD15718 | |||
Compositional bias | 193-212 | Pro residues | |||
Sequence conflict | 255 | in Ref. 1; AAD15718 | |||
Sequence conflict | 266 | in Ref. 1; AAD15718 | |||
Sequence conflict | 332 | in Ref. 1 | |||
Sequence conflict | 353 | in Ref. 1 | |||
Sequence conflict | 371 | in Ref. 1 | |||
Compositional bias | 402-418 | Pro residues | |||
Sequence conflict | 431 | in Ref. 1; AAD15718 | |||
Sequence conflict | 437 | in Ref. 1; AAD15718 | |||
Sequence conflict | 446 | in Ref. 1; AAD15718 | |||
Sequence conflict | 454-456 | in Ref. 1; AAD15718 | |||
Sequence conflict | 463 | in Ref. 1; AAD15718 | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF044669 EMBL· GenBank· DDBJ | AAD15718.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
BC082809 EMBL· GenBank· DDBJ | AAH82809.1 EMBL· GenBank· DDBJ | mRNA |