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Symbol ID2 contributors: mct/pgu - updated : 15-05-2014
HGNC name inhibitor of DNA binding 2, dominant negative helix-loop-helix protein
HGNC id 5361
Location 2p25.1      Physical location : 8.822.112 - 8.824.581
Synonym name
  • inhibitor of differentiation 2
  • DNA-binding protein inhibitor ID2
  • Synonym symbol(s) ID2A, ID2H, GIG8, MGC26389, ID-2, GIG8A, bHLHb26
    TYPE functioning gene
    STRUCTURE 2.47 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • contains several E-boxes within its promoter
  • GATA4 and SMAD4 cooperatively activated the ID2 promoter
  • NBN, RAD21, and TP63 lead to a repression of ID2 promoter activity
  • MAPPING cloned Y linked   status provisional
    Physical map
    FLJ30594 2p25.3 hypothetical protein FLJ30594 LOC391349 2 similar to phosphoinositide-3-kinase, catalytic, delta polypeptide; p110d; phosphatidylinositol 3-kinase, catalytic, delta polypeptide LOC129607 2p25.2 hypothetical protein LOC129607 cig5 2p25.2 viperin RNF144 2p25 ring finger protein 144 LOC129614 2p25.2 similar to acidic integral membrane protein LOC391350 2 similar to ENSANGP00000014942 ID2 2p25 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein KIDINS220 2p24 likely homolog of rat kinase D-interacting substance of 220 kDa LOC129642 2p25.2 hypothetical protein BC016005 DDEF2 2p24 development and differentiation enhancing factor 2 ITGB1BP1 2p25.2 integrin beta 1 binding protein 1 CPSF3 2pter-p25 cleavage and polyadenylation specific factor 3, 73kDa LOC285148 2p25.2 hypothetical protein LOC285148 ADAM17 2p25 a disintegrin and metalloproteinase domain 17 (tumor necrosis factor, alpha, converting enzyme) YWHAQ 2p25 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide TAF1B 2p25 TATA box binding protein (TBP)-associated factor, RNA polymerase I, B, 63kDa TFCP2L2 2p25.1 transcription factor CP2-like 2 TIEG2 2p25 TGFB inducible early growth response 2 RRM2 2p24 ribonucleotide reductase M2 polypeptide FLJ25102 2p25.1 hypothetical protein FLJ25102 HPCAL1 2p25.1 hippocalcin-like 1 ODC1 2p25 ornithine decarboxylase 1 LOC130063 2p25.1 hypothetical gene LOC130063 FLJ14075 2p25.1 hypothetical protein FLJ14075 ATP6V1C2 2p25.1 ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C isoform 2 P5 2p25.1 protein disulfide isomerase-related protein LOC388924 2 LOC388924 KCNF1 2p25 potassium voltage-gated channel, subfamily F, member 1 FLJ33534 2p25.1 hypothetical protein FLJ33534 LOC391351 2 similar to RPL6 protein FLJ25143 2p25.1 hypothetical protein FLJ25143 MGC33602 ROCK2 2p24 Rho-associated, coiled-coil containing protein kinase 2
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1402 - 134 - 1996 8649364
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineparathyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    cell lineage
    cell lines
    at STAGE
    physiological period
    Text early fetal tissues, including those of the central nervous system
    basic helix-loop-helix (bHLH) domain, lacking the DNA binding domain
    FAMILY inhibitor of DNA binding (ID) family
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • can sequester CLOCK and ARNTL1 to the cytoplasm
  • basic FUNCTION
  • inhibiting transcription factors of the basic helix loop helix family
  • proper expression of ID2 is important to achieving a fine balance between growth and differentiation during chondrogenesis
  • plays a dual role in skin tumorigenesis by suppressing tumor development through the establishment of epidermal gammadelta T cell-mediated skin immunosurveillance and by promoting tumor cell proliferation via the control of the cyclin D1 protein level
  • play important roles in controlling cell fate determination, differentiation, and proliferation of various cell
  • acts as a negative regulator of the differentiation of immature B cells occurring in the spleen, and MXD3 negatively regulates B cell differentiation in the spleen by inducing ID2 expression
  • promotes tumor cell migration and invasion through transcriptional repression of semaphorin 3F
  • major differentiation factors of the NK-cell lineage, including HOXA9, HOXA10 and ID2, were (de)regulated via polycomb repressor complex 2 (PRC2) which therefore contributes to T-cell leukemogenesis
  • play an essential role in the regulation of breast epithelial cell differentiation and proliferation
  • rhythmically expressed HLH transcriptional repressor
  • contributes to both input and output components of the clock and that this may be via interaction with the bHLH clock proteins CLOCK and ARNTL1
  • could potentially regulate aspects of both clock input and output through a time-of-day specific interaction with CLOCK and ARNTL1
  • acts as an oncogene and elevated levels of ID2 have been reported in several malignancies
  • ID2/TCF3 axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation
  • CELLULAR PROCESS nucleotide, transcription, regulation
  • calcineurin-NFATC4 signaling axis acts as a major regulator of Neural stem cells (NSCs)self-renewal and proliferation by promoting the expression of transcription factors (TFs), including ID2, that contribute to the maintenance of the NSC state
  • a component heterodimer with other HLH proteins
    small molecule
  • target of transcriptional activation by EWSR1-FLI1 and EWSR1-ERG, two fusion proteins characterizing Ewing family tumors
  • targets of MECP2 (role in regulation of neuronal maturation that may explain the molecular pathogenesis of RTT)
  • interacting with PDLIM5 (is a cytoplasmic sequestration factor for ID2 in normal and tumor cells from the nervous system)
  • interacting with OLIG2 (inhibiting posttranslationally OLIG2) (PMID :
  • interacting with SEMA3F, a potent inhibitor of metastasis, was repressed by ID2)
  • TP63, a key transcription factor in epithelial development and differentiation, binding specific cis-acting sequence within the ID2 gene promoter, not suppressing ID2 expression, but rather preventing excessive expression of that protein to enable the onset of keratinocyte differentiation
  • PRMT5 is required for maintaining the methylation status of CpG islands of ID2 and ID4 leading to gene silencing during glial cell differentiation
  • ID2 and RORC are sequentially up-regulated during lymphoid tissue inducer (LTi) cell development, matching two waves of differentiation with opposite requirements for NOTCH1 signaling
  • MYSM1 protein is associated with the ID2 locus
  • NFIL3 binds directly to the regulatory regions of both EOMES and ID2, promoting their transcription
  • ID2 acts to repress the TCF3-mediated trans-activation of the Il10 locus
  • cell & other
    repressed by ZBTB18, repressing ID1, ID2, ID3, ID4 genes during corticogenesis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in astrocytic tumors (PMID :
    tumoral     --over  
    ESRl-positive epithelial tumor cells indeed increases the cells invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors
    Variant & Polymorphism
    Candidate gene
    Therapy target