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MGP001642

UniProt Annotations

Entry Information
Gene Nameinsulinoma-associated 1
Protein EntryINSM1_HUMAN
UniProt IDQ01101
SpeciesHuman
Comments
Comment typeDescription
DomainThe C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.
FunctionSequence-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. {ECO:0000269|PubMed:11842116, ECO:0000269|PubMed:16511571, ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19124461}.
InductionUp-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3. {ECO:0000269|PubMed:12890672, ECO:0000269|PubMed:16511571}.
SimilarityBelongs to the INSM1 family. {ECO:0000305}.
SimilarityContains 5 C2H2-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00042}.
Subcellular LocationNucleus {ECO:0000250}.
SubunitInteracts (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. {ECO:0000250, ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19124461, ECO:0000269|Ref.11}.
Tissue SpecificityExpressed 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. {ECO:0000269|PubMed:12890672, ECO:0000269|PubMed:1634555}.
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