UniProtKB - Q63ZV0 (INSM1_MOUSE)
Protein
Insulinoma-associated protein 1
Gene
Insm1
Organism
Mus musculus (Mouse)
Status
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. 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.By similarity5 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 272 – 292 | C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 300 – 322 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 373 – 395 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 452 – 475 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 480 – 503 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 24 |
GO - Molecular functioni
- chromatin DNA binding Source: UniProtKB
- cyclin binding Source: MGI
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: MGI
- histone deacetylase binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
GO - Biological processi
- adrenal chromaffin cell differentiation Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- cell differentiation Source: MGI
- endocrine pancreas development Source: MGI
- endocrine system development Source: MGI
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of protein phosphorylation Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- neuron differentiation Source: GO_Central
- noradrenergic neuron development Source: UniProtKB
- norepinephrine biosynthetic process Source: UniProtKB
- pancreatic A cell differentiation Source: UniProtKB
- positive regulation of cell cycle arrest Source: UniProtKB
- positive regulation of cell differentiation Source: UniProtKB
- positive regulation of cell migration Source: MGI
- positive regulation of cell population proliferation Source: MGI
- positive regulation of neural precursor cell proliferation Source: UniProtKB
- regulation of cell cycle process Source: GO_Central
- regulation of gene expression Source: UniProtKB
- regulation of protein-containing complex assembly Source: UniProtKB
- sympathetic ganglion development Source: UniProtKB
- transdifferentiation Source: UniProtKB
- type B pancreatic cell development Source: MGI
- type B pancreatic cell differentiation Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, DNA-binding, Repressor |
Biological process | Cell cycle, Differentiation, Neurogenesis, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Insulinoma-associated protein 1Alternative name(s): Zinc finger protein IA-1 |
Gene namesi | Name:Insm1 Synonyms:Ia1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1859980, Insm1 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleus Source: MGI
Other locations
- transcription repressor complex Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
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.3 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000047269 | 1 – 521 | Insulinoma-associated protein 1Add BLAST | 521 |
Proteomic databases
MaxQBi | Q63ZV0 |
PaxDbi | Q63ZV0 |
PRIDEi | Q63ZV0 |
PTM databases
iPTMneti | Q63ZV0 |
PhosphoSitePlusi | Q63ZV0 |
Expressioni
Tissue specificityi
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.3 Publications
Developmental stagei
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 chord 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.7 Publications
Gene expression databases
Bgeei | ENSMUSG00000068154, Expressed in islet of Langerhans and 202 other tissues |
ExpressionAtlasi | Q63ZV0, baseline and differential |
Genevisiblei | Q63ZV0, MM |
Interactioni
Subunit structurei
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.
By similarity2 PublicationsGO - Molecular functioni
- cyclin binding Source: MGI
- histone deacetylase binding Source: MGI
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000092048 |
Miscellaneous databases
RNActi | Q63ZV0, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 20 | SNAG domain1 PublicationAdd BLAST | 20 | |
Regioni | 2 – 7 | Required and sufficient for interaction with KDM1ABy similarity | 6 | |
Regioni | 43 – 56 | Necessary for interaction with CCND1By similarityAdd BLAST | 14 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 250 | Gly/Pro-richAdd BLAST | 250 | |
Compositional biasi | 405 – 414 | Pro-rich | 10 |
Domaini
The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.By similarity
Sequence similaritiesi
Belongs to the INSM1 family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 272 – 292 | C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 300 – 322 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 373 – 395 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 452 – 475 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 480 – 503 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 24 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG3993, Eukaryota |
GeneTreei | ENSGT00940000162552 |
HOGENOMi | CLU_033476_1_0_1 |
InParanoidi | Q63ZV0 |
OMAi | REHEKHK |
OrthoDBi | 1306883at2759 |
PhylomeDBi | Q63ZV0 |
TreeFami | TF320538 |
Family and domain databases
InterProi | View protein in InterPro IPR042972, INSM1/2 IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR15065, PTHR15065, 1 hit |
Pfami | View protein in Pfam PF00096, zf-C2H2, 4 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 5 hits |
SUPFAMi | SSF57667, SSF57667, 3 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 4 hits PS50157, ZINC_FINGER_C2H2_2, 4 hits |
i Sequence
Sequence statusi: Complete.
Q63ZV0-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPRGFLVKRS KKSTPVSYRV RGGEDSDRAL LLSPGCGGAR AEPPVPSPGP
60 70 80 90 100
LPPPPPPALA ERAHAALAAA LACAPGPPPP PPPGPRAAHF GNPEAAHPAP
110 120 130 140 150
LYSPTRPVSR EHEKHKYFER SFNLGSPVSA ESFPTPAALL AGGGSGANGA
160 170 180 190 200
GGGGGGTCGG DALLFAPAEL KMGTAFSAGA EAARGPGTGP PLSPAAALRP
210 220 230 240 250
PGKRPAPPAA VATEPPAKAA KAPSAKKPKA IRKLHFEDEV TTSPVLGLKI
260 270 280 290 300
KEGPVEAPRG RAGGATRPLG EFICQLCKEE YADPFALAQH KCSRIVRVEY
310 320 330 340 350
RCPECAKVFS CPANLASHRR WHKPRPVPAA ARAPEPEAAT RAEAREAAGG
360 370 380 390 400
GSSDRDTPSP GGVSESGSED GLYECHHCAK KFRRQAYLRK HLLAHHQALQ
410 420 430 440 450
AKGAPPPPPP PPPPAEDILA FYAGPDEKAP QEASGDGEAA GVLGLSATAQ
460 470 480 490 500
CHLCPVCGET FPSKGAQERH LRLLHAAQVF PCKYCPATFY SSPGLTRHIN
510 520
KCHPSENRQV ILLQVPVRPA C
Sequence cautioni
The sequence AAD15718 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 59 | L → R in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 255 | V → L in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 266 | T → A in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 332 | R → G (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 353 | S → T (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 371 | G → R (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 431 | Q → H in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 437 | G → S in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 446 | S → N in AAD15718 (PubMed:12079283).Curated | 1 | |
Sequence conflicti | 454 – 456 | CPV → FPL in AAD15718 (PubMed:12079283).Curated | 3 | |
Sequence conflicti | 463 | S → T in AAD15718 (PubMed:12079283).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF044669 mRNA Translation: AAD15718.1 Frameshift. BC082809 mRNA Translation: AAH82809.1 |
CCDSi | CCDS16830.1 |
RefSeqi | NP_058585.2, NM_016889.3 |
Genome annotation databases
Ensembli | ENSMUST00000089257; ENSMUSP00000092048; ENSMUSG00000068154 |
GeneIDi | 53626 |
KEGGi | mmu:53626 |
UCSCi | uc008msh.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF044669 mRNA Translation: AAD15718.1 Frameshift. BC082809 mRNA Translation: AAH82809.1 |
CCDSi | CCDS16830.1 |
RefSeqi | NP_058585.2, NM_016889.3 |
3D structure databases
SMRi | Q63ZV0 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000092048 |
PTM databases
iPTMneti | Q63ZV0 |
PhosphoSitePlusi | Q63ZV0 |
Proteomic databases
MaxQBi | Q63ZV0 |
PaxDbi | Q63ZV0 |
PRIDEi | Q63ZV0 |
Protocols and materials databases
Antibodypediai | 9637, 81 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000089257; ENSMUSP00000092048; ENSMUSG00000068154 |
GeneIDi | 53626 |
KEGGi | mmu:53626 |
UCSCi | uc008msh.2, mouse |
Organism-specific databases
CTDi | 3642 |
MGIi | MGI:1859980, Insm1 |
Phylogenomic databases
eggNOGi | KOG3993, Eukaryota |
GeneTreei | ENSGT00940000162552 |
HOGENOMi | CLU_033476_1_0_1 |
InParanoidi | Q63ZV0 |
OMAi | REHEKHK |
OrthoDBi | 1306883at2759 |
PhylomeDBi | Q63ZV0 |
TreeFami | TF320538 |
Miscellaneous databases
BioGRID-ORCSi | 53626, 0 hits in 17 CRISPR screens |
ChiTaRSi | Insm1, mouse |
PROi | PR:Q63ZV0 |
RNActi | Q63ZV0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000068154, Expressed in islet of Langerhans and 202 other tissues |
ExpressionAtlasi | Q63ZV0, baseline and differential |
Genevisiblei | Q63ZV0, MM |
Family and domain databases
InterProi | View protein in InterPro IPR042972, INSM1/2 IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR15065, PTHR15065, 1 hit |
Pfami | View protein in Pfam PF00096, zf-C2H2, 4 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 5 hits |
SUPFAMi | SSF57667, SSF57667, 3 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 4 hits PS50157, ZINC_FINGER_C2H2_2, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | INSM1_MOUSE | |
Accessioni | Q63ZV0Primary (citable) accession number: Q63ZV0 Secondary accession number(s): Q9Z113 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2005 |
Last sequence update: | October 25, 2004 | |
Last modified: | February 10, 2021 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families