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Protein

Insulinoma-associated protein 1

Gene

Insm1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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)DescriptionActionsGraphical viewLength
Zinc fingeri272 – 292C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST21
Zinc fingeri300 – 322C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri373 – 395C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri452 – 475C2H2-type 4PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri480 – 503C2H2-type 5PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

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 proliferation Source: UniProtKB
  • negative regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • 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 proliferation Source: MGI
  • positive regulation of neural precursor cell proliferation Source: UniProtKB
  • regulation of gene expression Source: UniProtKB
  • regulation of protein complex assembly Source: UniProtKB
  • sympathetic ganglion development Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • transdifferentiation Source: UniProtKB
  • type B pancreatic cell development Source: MGI
  • type B pancreatic cell differentiation Source: UniProtKB
Complete GO annotation...

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

ReactomeiR-MMU-210746. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulinoma-associated protein 1
Alternative name(s):
Zinc finger protein IA-1
Gene namesi
Name:Insm1
Synonyms:Ia1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1859980. Insm1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • nucleus Source: MGI
  • transcriptional repressor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000472691 – 521Insulinoma-associated protein 1Add BLAST521

Proteomic databases

MaxQBiQ63ZV0.
PaxDbiQ63ZV0.
PRIDEiQ63ZV0.

PTM databases

iPTMnetiQ63ZV0.
PhosphoSitePlusiQ63ZV0.

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

BgeeiENSMUSG00000068154.
CleanExiMM_INSM1.
ExpressionAtlasiQ63ZV0. baseline and differential.
GenevisibleiQ63ZV0. 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 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092048.

Structurei

3D structure databases

ProteinModelPortaliQ63ZV0.
SMRiQ63ZV0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 20SNAG domainBy similarityAdd BLAST20
Regioni43 – 56Necessary for interaction with CCND1By similarityAdd BLAST14

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 250Gly/Pro-richAdd BLAST250
Compositional biasi405 – 414Pro-rich10

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
Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri272 – 292C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST21
Zinc fingeri300 – 322C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri373 – 395C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri452 – 475C2H2-type 4PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri480 – 503C2H2-type 5PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3993. Eukaryota.
ENOG4111MVC. LUCA.
GeneTreeiENSGT00530000064190.
HOGENOMiHOG000113079.
HOVERGENiHBG052137.
InParanoidiQ63ZV0.
OMAiAPAELKM.
OrthoDBiEOG091G0BI3.
PhylomeDBiQ63ZV0.
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]
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.

Q63ZV0-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:521
Mass (Da):54,050
Last modified:October 25, 2004 - v1
Checksum:i84D0D8E64504D351
GO

Sequence cautioni

The sequence AAD15718 differs from that shown. Reason: Frameshift at positions 329 and 369.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti59L → R in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti255V → L in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti266T → A in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti332R → G (PubMed:12079283).Curated1
Sequence conflicti353S → T (PubMed:12079283).Curated1
Sequence conflicti371G → R (PubMed:12079283).Curated1
Sequence conflicti431Q → H in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti437G → S in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti446S → N in AAD15718 (PubMed:12079283).Curated1
Sequence conflicti454 – 456CPV → FPL in AAD15718 (PubMed:12079283).Curated3
Sequence conflicti463S → T in AAD15718 (PubMed:12079283).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044669 mRNA. Translation: AAD15718.1. Frameshift.
BC082809 mRNA. Translation: AAH82809.1.
CCDSiCCDS16830.1.
RefSeqiNP_058585.2. NM_016889.3.
UniGeneiMm.379070.

Genome annotation databases

EnsembliENSMUST00000089257; ENSMUSP00000092048; ENSMUSG00000068154.
GeneIDi53626.
KEGGimmu:53626.
UCSCiuc008msh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044669 mRNA. Translation: AAD15718.1. Frameshift.
BC082809 mRNA. Translation: AAH82809.1.
CCDSiCCDS16830.1.
RefSeqiNP_058585.2. NM_016889.3.
UniGeneiMm.379070.

3D structure databases

ProteinModelPortaliQ63ZV0.
SMRiQ63ZV0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092048.

PTM databases

iPTMnetiQ63ZV0.
PhosphoSitePlusiQ63ZV0.

Proteomic databases

MaxQBiQ63ZV0.
PaxDbiQ63ZV0.
PRIDEiQ63ZV0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000089257; ENSMUSP00000092048; ENSMUSG00000068154.
GeneIDi53626.
KEGGimmu:53626.
UCSCiuc008msh.2. mouse.

Organism-specific databases

CTDi3642.
MGIiMGI:1859980. Insm1.

Phylogenomic databases

eggNOGiKOG3993. Eukaryota.
ENOG4111MVC. LUCA.
GeneTreeiENSGT00530000064190.
HOGENOMiHOG000113079.
HOVERGENiHBG052137.
InParanoidiQ63ZV0.
OMAiAPAELKM.
OrthoDBiEOG091G0BI3.
PhylomeDBiQ63ZV0.
TreeFamiTF320538.

Enzyme and pathway databases

ReactomeiR-MMU-210746. Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.

Miscellaneous databases

ChiTaRSiInsm1. mouse.
PROiQ63ZV0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000068154.
CleanExiMM_INSM1.
ExpressionAtlasiQ63ZV0. baseline and differential.
GenevisibleiQ63ZV0. MM.

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]
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiINSM1_MOUSE
AccessioniPrimary (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: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.