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Q01101 (INSM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulinoma-associated protein 1
Alternative name(s):
Zinc finger protein IA-1
Gene names
Name:INSM1
Synonyms:IA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length510 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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. Ref.4 Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

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-terminus 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. Ref.6 Ref.8 Ref.9

Subcellular location

Nucleus By similarity.

Tissue specificity

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. Ref.1 Ref.5

Induction

Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3. Ref.5 Ref.7

Domain

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

Sequence similarities

Belongs to the INSM1 family.

Contains 5 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processCell cycle
Differentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionDevelopmental protein
Repressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadrenal chromaffin cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of protein phosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.4Ref.6Ref.8Ref.9. Source: UniProtKB

noradrenergic neuron development

Inferred from sequence or structural similarity. Source: UniProtKB

norepinephrine biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

pancreatic A cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell cycle arrest

Inferred from direct assay Ref.9. Source: UniProtKB

positive regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neural precursor cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein complex assembly

Inferred from direct assay Ref.9. Source: UniProtKB

sympathetic ganglion development

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transdifferentiation

Inferred from direct assay Ref.7. Source: UniProtKB

type B pancreatic cell development

Inferred from electronic annotation. Source: Ensembl

type B pancreatic cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componenttranscriptional repressor complex

Inferred from direct assay Ref.6Ref.8. Source: UniProtKB

   Molecular_functionchromatin DNA binding

Inferred from direct assay Ref.6Ref.8. Source: UniProtKB

core promoter binding

Inferred from direct assay Ref.4Ref.6Ref.8. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.4Ref.6Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 510510Insulinoma-associated protein 1
PRO_0000047268

Regions

Zinc finger267 – 28721C2H2-type 1; atypical
Zinc finger295 – 31723C2H2-type 2
Zinc finger367 – 38923C2H2-type 3
Zinc finger441 – 46424C2H2-type 4
Zinc finger469 – 49224C2H2-type 5
Region1 – 2020SNAG domain By similarity
Region43 – 5816Necessary for interaction with CCND1
Compositional bias1 – 250250Ala/Gly/Pro-rich

Experimental info

Mutagenesis43 – 5816PPAPS…PPPPP → LLALSLVLGLLLLLLL: Inhibits weakly translational repression activity. Inhibits interaction with CCND1 and cell cycle arrest. Ref.9

Secondary structure

........... 510
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q01101 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 22D4E97696397365

FASTA51052,923
        10         20         30         40         50         60 
MPRGFLVKRS KKSTPVSYRV RGGEDGDRAL LLSPSCGGAR AEPPAPSPVP GPLPPPPPAE 

        70         80         90        100        110        120 
RAHAALAAAL ACAPGPQPPP QGPRAAHFGN PEAAHPAPLY SPTRPVSREH EKHKYFERSF 

       130        140        150        160        170        180 
NLGSPVSAES FPTPAALLGG GGGGGASGAG GGGTCGGDPL LFAPAELKMG TAFSAGAEAA 

       190        200        210        220        230        240 
RGPGPGPPLP PAAALRPPGK RPPPPTAAEP PAKAVKAPGA KKPKAIRKLH FEDEVTTSPV 

       250        260        270        280        290        300 
LGLKIKEGPV EAPRGRAGGA ARPLGEFICQ LCKEEYADPF ALAQHKCSRI VRVEYRCPEC 

       310        320        330        340        350        360 
AKVFSCPANL ASHRRWHKPR PAPAAARAPE PEAAARAEAR EAPGGGSDRD TPSPGGVSES 

       370        380        390        400        410        420 
GSEDGLYECH HCAKKFRRQA YLRKHLLAHH QALQAKGAPL APPAEDLLAL YPGPDEKAPQ 

       430        440        450        460        470        480 
EAAGDGEGAG VLGLSASAEC HLCPVCGESF ASKGAQERHL RLLHAAQVFP CKYCPATFYS 

       490        500        510 
SPGLTRHINK CHPSENRQVI LLQVPVRPAC 

« Hide

References

« Hide 'large scale' references
[1]"A novel human insulinoma-associated cDNA, IA-1, encodes a protein with 'zinc-finger' DNA-binding motifs."
Goto Y., de Silva M.G., Toscani A., Prabhakar B.S., Notkins A.L., Lan M.S.
J. Biol. Chem. 267:15252-15257(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1."
Lan M.S., Li Q., Lu J., Modi W.S., Notkins A.L.
J. Biol. Chem. 269:14170-14174(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
[4]"Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence."
Breslin M.B., Zhu M., Notkins A.L., Lan M.S.
Nucleic Acids Res. 30:1038-1045(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[5]"NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system."
Breslin M.B., Zhu M., Lan M.S.
J. Biol. Chem. 278:38991-38997(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY.
[6]"INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases."
Liu W.D., Wang H.W., Muguira M., Breslin M.B., Lan M.S.
Biochem. J. 397:169-177(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1; HDAC1 AND HDAC3.
[7]"IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas."
Mellitzer G., Bonne S., Luco R.F., Van De Casteele M., Lenne-Samuel N., Collombat P., Mansouri A., Lee J., Lan M., Pipeleers D., Nielsen F.C., Ferrer J., Gradwohl G., Heimberg H.
EMBO J. 25:1344-1352(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[8]"Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription."
Wang H.W., Muguira M., Liu W.D., Zhang T., Chen C., Aucoin R., Breslin M.B., Lan M.S.
J. Endocrinol. 198:29-39(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1 AND HDAC3.
[9]"Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest."
Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.
J. Biol. Chem. 284:5574-5581(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH CCND1, MUTAGENESIS OF 43-PRO--PRO-58.
[10]"Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation."
Lan M.S., Breslin M.B.
FASEB J. 23:2024-2033(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Solution NMR structure of C2H2-type zinc-fingers 4 and 5 from human insulinoma-associated protein 1 (fragment 424-497), Northeast structural genomics consortium target HR7614B (Casp target)."
Northeast structural genomics consortium (NESG)
Submitted (OCT-2012) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 424-497 IN COMPLEX WITH ZINC IONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M93119 mRNA. Translation: AAA58680.1.
AL161658 Genomic DNA. Translation: CAC36065.1.
U07172 Genomic DNA. Translation: AAA20938.1.
PIRA42750.
RefSeqNP_002187.1. NM_002196.2.
UniGeneHs.89584.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LV2NMR-A424-497[»]
3ZMSX-ray2.96C2-510[»]
ProteinModelPortalQ01101.
SMRQ01101. Positions 213-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109853. 5 interactions.
IntActQ01101. 3 interactions.
MINTMINT-1395936.
STRING9606.ENSP00000312631.

PTM databases

PhosphoSiteQ01101.

Polymorphism databases

DMDM547700.

Proteomic databases

PaxDbQ01101.
PRIDEQ01101.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310227; ENSP00000312631; ENSG00000173404.
GeneID3642.
KEGGhsa:3642.
UCSCuc002wrx.3. human.

Organism-specific databases

CTD3642.
GeneCardsGC20P020348.
HGNCHGNC:6090. INSM1.
MIM600010. gene.
neXtProtNX_Q01101.
PharmGKBPA29897.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG308747.
HOGENOMHOG000113079.
HOVERGENHBG052137.
InParanoidQ01101.
OMAREHEKHK.
OrthoDBEOG7JMGDD.
PhylomeDBQ01101.
TreeFamTF320538.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
SignaLinkQ01101.

Gene expression databases

BgeeQ01101.
CleanExHS_INSM1.
GenevestigatorQ01101.

Family and domain databases

Gene3D3.30.160.60. 1 hit.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00096. zf-C2H2. 4 hits.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiINSM1.
GenomeRNAi3642.
NextBio14255.
PROQ01101.
SOURCESearch...

Entry information

Entry nameINSM1_HUMAN
AccessionPrimary (citable) accession number: Q01101
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: March 19, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM