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Protein

DNA-binding protein inhibitor ID-3

Gene

Id3

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

Functioni

Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.3 Publications

GO - Molecular functioni

  • protein domain specific binding Source: MGI
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • central nervous system development Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • epithelial cell differentiation Source: MGI
  • heart development Source: MGI
  • metanephros development Source: UniProtKB
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of myoblast differentiation Source: UniProtKB
  • negative regulation of osteoblast differentiation Source: MGI
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • neuron differentiation Source: Ensembl
  • notochord development Source: UniProtKB
  • odontogenesis Source: UniProtKB
  • positive regulation of apoptotic process Source: Ensembl
  • regulation of cell cycle Source: Ensembl
  • regulation of DNA replication Source: Ensembl
  • response to wounding Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Biological rhythms, Myogenesis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
DNA-binding protein inhibitor ID-3
Alternative name(s):
ID-like protein inhibitor HLH 462
Inhibitor of DNA binding 3
Inhibitor of differentiation 3
Gene namesi
Name:Id3
Synonyms:Hlh462, Id-3, Idb3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:96398. Id3.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication
  • Cytoplasm 1 Publication

  • Note: Nuclear in proliferating cells, translocates to cytosol during cell differentiation.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • microtubule cytoskeleton Source: MGI
  • nucleoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 119119DNA-binding protein inhibitor ID-3PRO_0000127248Add
BLAST

Post-translational modificationi

Polyubiquitinated; which is favored by Ifi204 and leads to proteasomal degradation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiP41133.
PRIDEiP41133.

PTM databases

PhosphoSiteiP41133.

Expressioni

Tissue specificityi

Expressed by myoblasts (at protein level).1 Publication

Inductioni

By a variety of mitogenic agents in serum starved cells. Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain and heart with peak levels between CT16 and CT20 in SCN and between CT8 and CT12 in the heart.1 Publication

Gene expression databases

BgeeiP41133.
CleanExiMM_ID3.
ExpressionAtlasiP41133. baseline and differential.
GenevisibleiP41133. MM.

Interactioni

Subunit structurei

Homodimer, and heterodimer with other HLH proteins. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with COPS5 and COPS7A. Interacts with IFI204. Interacts with GATA4 and NKX2-5. Interacts with ANKRD2; both proteins cooperate in myoblast differentiation.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ankrd2Q9WV064EBI-309448,EBI-8854438

Protein-protein interaction databases

BioGridi200507. 11 interactions.
IntActiP41133. 4 interactions.
STRINGi10090.ENSMUSP00000008016.

Structurei

3D structure databases

ProteinModelPortaliP41133.
SMRiP41133. Positions 32-83.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 8053bHLHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni35 – 8753Interaction with IFI204By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG83634.
GeneTreeiENSGT00390000000908.
HOGENOMiHOG000234788.
HOVERGENiHBG009009.
InParanoidiP41133.
KOiK17694.
OMAiPARGCYE.
OrthoDBiEOG7X9G8G.
PhylomeDBiP41133.
TreeFamiTF326217.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR026052. DNA-bd_prot-inh.
[Graphical view]
PANTHERiPTHR11723. PTHR11723. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P41133-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKALSPVRGC YEAVCCLSER SLAIARGRGK SPSTEEPLSL LDDMNHCYSR
60 70 80 90 100
LRELVPGVPR GTQLSQVEIL QRVIDYILDL QVVLAEPAPG PPDGPHLPIQ
110
TAELTPELVI SKDKRSFCH
Length:119
Mass (Da):13,089
Last modified:February 1, 1995 - v1
Checksum:i49F3B841D2D2BF15
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60523 mRNA. Translation: AAA37818.1.
CCDSiCCDS18800.1.
PIRiA39114.
RefSeqiNP_032347.1. NM_008321.2.
UniGeneiMm.110.

Genome annotation databases

EnsembliENSMUST00000008016; ENSMUSP00000008016; ENSMUSG00000007872.
GeneIDi15903.
KEGGimmu:15903.
UCSCiuc012dnf.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60523 mRNA. Translation: AAA37818.1.
CCDSiCCDS18800.1.
PIRiA39114.
RefSeqiNP_032347.1. NM_008321.2.
UniGeneiMm.110.

3D structure databases

ProteinModelPortaliP41133.
SMRiP41133. Positions 32-83.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200507. 11 interactions.
IntActiP41133. 4 interactions.
STRINGi10090.ENSMUSP00000008016.

PTM databases

PhosphoSiteiP41133.

Proteomic databases

MaxQBiP41133.
PRIDEiP41133.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000008016; ENSMUSP00000008016; ENSMUSG00000007872.
GeneIDi15903.
KEGGimmu:15903.
UCSCiuc012dnf.1. mouse.

Organism-specific databases

CTDi3399.
MGIiMGI:96398. Id3.

Phylogenomic databases

eggNOGiNOG83634.
GeneTreeiENSGT00390000000908.
HOGENOMiHOG000234788.
HOVERGENiHBG009009.
InParanoidiP41133.
KOiK17694.
OMAiPARGCYE.
OrthoDBiEOG7X9G8G.
PhylomeDBiP41133.
TreeFamiTF326217.

Miscellaneous databases

NextBioi288628.
PROiP41133.
SOURCEiSearch...

Gene expression databases

BgeeiP41133.
CleanExiMM_ID3.
ExpressionAtlasiP41133. baseline and differential.
GenevisibleiP41133. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR026052. DNA-bd_prot-inh.
[Graphical view]
PANTHERiPTHR11723. PTHR11723. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene."
    Christy B.A., Sanders L.K., Lau L.F., Copeland N.G., Jenkins N.A., Nathans D.
    Proc. Natl. Acad. Sci. U.S.A. 88:1815-1819(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins."
    Liu C.-J., Ding B., Wang H., Lengyel P.
    Mol. Cell. Biol. 22:2893-2905(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IFI204.
  3. "Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9 signalosome."
    Berse M., Bounpheng M., Huang X., Christy B., Pollmann C., Dubiel W.
    J. Mol. Biol. 343:361-370(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COPS5 AND COPS7A.
  4. "p204 protein overcomes the inhibition of the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes by Id proteins."
    Ding B., Liu C.-J., Huang Y., Yu J., Kong W., Lengyel P.
    J. Biol. Chem. 281:14893-14906(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GATA4 AND NKX2-5, UBIQUITINATION, SUBCELLULAR LOCATION.
  5. "A role for Id2 in regulating photic entrainment of the mammalian circadian system."
    Duffield G.E., Watson N.P., Mantani A., Peirson S.N., Robles-Murguia M., Loros J.J., Israel M.A., Dunlap J.C.
    Curr. Biol. 19:297-304(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  6. "Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the proliferation of muscle precursor cells by an epigenetic mechanism."
    Diao Y., Guo X., Li Y., Sun K., Lu L., Jiang L., Fu X., Zhu H., Sun H., Wang H., Wu Z.
    Cell Stem Cell 11:231-241(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Ankyrin repeat domain protein 2 and inhibitor of DNA binding 3 cooperatively inhibit myoblast differentiation by physical interaction."
    Mohamed J.S., Lopez M.A., Cox G.A., Boriek A.M.
    J. Biol. Chem. 288:24560-24568(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MYOBLAST DIFFERENTIATION, INTERACTION WITH ANKRD2, TISSUE SPECIFICITY.

Entry informationi

Entry nameiID3_MOUSE
AccessioniPrimary (citable) accession number: P41133
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 22, 2015
This is version 122 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

External Data

Dasty 3

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 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.