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Protein

Insulinoma-associated protein 1

Gene

INSM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 fingeri267 – 287C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST21
Zinc fingeri295 – 317C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri367 – 389C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri441 – 464C2H2-type 4PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri469 – 492C2H2-type 5PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Repressor
Biological processCell cycle, Differentiation, Neurogenesis, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-210746 Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells
SignaLinkiQ01101
SIGNORiQ01101

Names & Taxonomyi

Protein namesi
Recommended name:
Insulinoma-associated protein 1
Alternative name(s):
Zinc finger protein IA-1
Gene namesi
Name:INSM1
Synonyms:IA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000173404.4
HGNCiHGNC:6090 INSM1
MIMi600010 gene
neXtProtiNX_Q01101

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi43 – 58PPAPS…PPPPP → LLALSLVLGLLLLLLL: Inhibits weakly translational repression activity. Inhibits interaction with CCND1 and cell cycle arrest. 1 PublicationAdd BLAST16

Organism-specific databases

DisGeNETi3642
OpenTargetsiENSG00000173404
PharmGKBiPA29897

Polymorphism and mutation databases

BioMutaiINSM1
DMDMi547700

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000472681 – 510Insulinoma-associated protein 1Add BLAST510

Proteomic databases

EPDiQ01101
PaxDbiQ01101
PeptideAtlasiQ01101
PRIDEiQ01101
ProteomicsDBi57916

PTM databases

iPTMnetiQ01101
PhosphoSitePlusiQ01101

Expressioni

Tissue specificityi

Expressed 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.2 Publications

Inductioni

Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3.2 Publications

Gene expression databases

BgeeiENSG00000173404 Expressed in 92 organ(s), highest expression level in brain
CleanExiHS_INSM1
GenevisibleiQ01101 HS

Interactioni

Subunit structurei

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 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.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109853, 5 interactors
IntActiQ01101, 10 interactors
STRINGi9606.ENSP00000312631

Structurei

Secondary structure

1510
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP01023
ProteinModelPortaliQ01101
SMRiQ01101
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 20SNAG domainBy similarityAdd BLAST20
Regioni43 – 58Necessary for interaction with CCND1Add BLAST16

Compositional bias

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

Domaini

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

Sequence similaritiesi

Belongs to the INSM1 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri267 – 287C2H2-type 1; atypicalPROSITE-ProRule annotationAdd BLAST21
Zinc fingeri295 – 317C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri367 – 389C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri441 – 464C2H2-type 4PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri469 – 492C2H2-type 5PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3993 Eukaryota
ENOG4111MVC LUCA
GeneTreeiENSGT00530000064190
HOGENOMiHOG000113079
HOVERGENiHBG052137
InParanoidiQ01101
OMAiAPAELKM
OrthoDBiEOG091G0BI3
PhylomeDBiQ01101
TreeFamiTF320538

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 4 hits
PS50157 ZINC_FINGER_C2H2_2, 4 hits

Sequencei

Sequence statusi: Complete.

Q01101-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPRGFLVKRS KKSTPVSYRV RGGEDGDRAL LLSPSCGGAR AEPPAPSPVP
60 70 80 90 100
GPLPPPPPAE RAHAALAAAL ACAPGPQPPP QGPRAAHFGN PEAAHPAPLY
110 120 130 140 150
SPTRPVSREH EKHKYFERSF NLGSPVSAES FPTPAALLGG GGGGGASGAG
160 170 180 190 200
GGGTCGGDPL LFAPAELKMG TAFSAGAEAA RGPGPGPPLP PAAALRPPGK
210 220 230 240 250
RPPPPTAAEP PAKAVKAPGA KKPKAIRKLH FEDEVTTSPV LGLKIKEGPV
260 270 280 290 300
EAPRGRAGGA ARPLGEFICQ LCKEEYADPF ALAQHKCSRI VRVEYRCPEC
310 320 330 340 350
AKVFSCPANL ASHRRWHKPR PAPAAARAPE PEAAARAEAR EAPGGGSDRD
360 370 380 390 400
TPSPGGVSES GSEDGLYECH HCAKKFRRQA YLRKHLLAHH QALQAKGAPL
410 420 430 440 450
APPAEDLLAL YPGPDEKAPQ EAAGDGEGAG VLGLSASAEC HLCPVCGESF
460 470 480 490 500
ASKGAQERHL RLLHAAQVFP CKYCPATFYS SPGLTRHINK CHPSENRQVI
510
LLQVPVRPAC
Length:510
Mass (Da):52,923
Last modified:June 1, 1994 - v1
Checksum:i22D4E97696397365
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M93119 mRNA Translation: AAA58680.1
AL161658 Genomic DNA No translation available.
U07172 Genomic DNA Translation: AAA20938.1
CCDSiCCDS13143.1
PIRiA42750
RefSeqiNP_002187.1, NM_002196.2
UniGeneiHs.89584

Genome annotation databases

EnsembliENST00000310227; ENSP00000312631; ENSG00000173404
GeneIDi3642
KEGGihsa:3642
UCSCiuc002wrx.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M93119 mRNA Translation: AAA58680.1
AL161658 Genomic DNA No translation available.
U07172 Genomic DNA Translation: AAA20938.1
CCDSiCCDS13143.1
PIRiA42750
RefSeqiNP_002187.1, NM_002196.2
UniGeneiHs.89584

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LV2NMR-A424-497[»]
3ZMSX-ray2.96C2-510[»]
DisProtiDP01023
ProteinModelPortaliQ01101
SMRiQ01101
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109853, 5 interactors
IntActiQ01101, 10 interactors
STRINGi9606.ENSP00000312631

PTM databases

iPTMnetiQ01101
PhosphoSitePlusiQ01101

Polymorphism and mutation databases

BioMutaiINSM1
DMDMi547700

Proteomic databases

EPDiQ01101
PaxDbiQ01101
PeptideAtlasiQ01101
PRIDEiQ01101
ProteomicsDBi57916

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310227; ENSP00000312631; ENSG00000173404
GeneIDi3642
KEGGihsa:3642
UCSCiuc002wrx.4 human

Organism-specific databases

CTDi3642
DisGeNETi3642
EuPathDBiHostDB:ENSG00000173404.4
GeneCardsiINSM1
HGNCiHGNC:6090 INSM1
MIMi600010 gene
neXtProtiNX_Q01101
OpenTargetsiENSG00000173404
PharmGKBiPA29897
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3993 Eukaryota
ENOG4111MVC LUCA
GeneTreeiENSGT00530000064190
HOGENOMiHOG000113079
HOVERGENiHBG052137
InParanoidiQ01101
OMAiAPAELKM
OrthoDBiEOG091G0BI3
PhylomeDBiQ01101
TreeFamiTF320538

Enzyme and pathway databases

ReactomeiR-HSA-210746 Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells
SignaLinkiQ01101
SIGNORiQ01101

Miscellaneous databases

GeneWikiiINSM1
GenomeRNAii3642
PROiPR:Q01101
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173404 Expressed in 92 organ(s), highest expression level in brain
CleanExiHS_INSM1
GenevisibleiQ01101 HS

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 4 hits
PS50157 ZINC_FINGER_C2H2_2, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiINSM1_HUMAN
AccessioniPrimary (citable) accession number: Q01101
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 7, 2018
This is version 156 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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