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FLASH GENE
Symbol TIMP2 contributors: mct - updated : 01-07-2021
HGNC name TIMP metallopeptidase inhibitor 2
HGNC id 11821
Location 17q25.3      Physical location : 76.849.062 - 76.921.472
Synonym name
  • tissue inhibitor of metalloproteinase 2
  • testicular secretory protein Li 57
  • Synonym symbol(s) CSC-21K, TIMP-2, DDC8
    DNA
    TYPE functioning gene
    SPECIAL FEATURE gene in gene, antisens
    text may be embedded in one intron of SYN4, as other TIMPs are in other SYNs
    STRUCTURE 72.41 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure five Sbeta1, two AP-2, one AP-1, three PEA-3
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 polyA site 3670 21.75 220 - 1992 1427908
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis    Rattus norvegicusFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Rattus norvegicusFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 12 cysteine residues that form six disulfide bridges
  • conjugated MetalloP
    HOMOLOGY
    Homologene
    FAMILY
  • protease inhibitor I35 (TIMP) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • inhibits all MMPs
  • erythroid potentiating and cell growth-promoting activities
  • inhibits endothelial cell growth
  • reduces tumor growth when it's overexpressed
  • participates in metanephric mesenchymal growth and in morphogenesis of the ureteric bud
  • antiapoptotic activity
  • with MMP14, control cell proliferation and migration through a non-proteolytic mechanism
  • role for MMP14/TIMP-2 interaction, in controling cell functions by a mechanism independent of extracellular matrix degradation
  • inhibiting ADAM12 and ADAM17
  • TIMP2 and TIMP3 play fundamental and differential roles in mediating pathological remodelling, independent from their MMP-inhibitory function
  • is a promiscuous MMP inhibitor that is ubiquitously expressed in normal tissues
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • may be associated with SYN4
  • positive regulator of MMP14 by promoting the availability of MMP14 at the all surface and supporting pericellular proteolysis (complex trimolecular MMP-14, TIMP2, proMMP2)
  • binding MMPs in a 1:1 stoechiometry
  • binding to MMP14 induces activation of ERK1/2 by a mechanism that does not require the proteolytic activity and is mediated by the cytoplasmic tail of MMP14
  • MMP10 interacting with tissue inhibitors of metalloproteinases TIMP1 and TIMP2
  • MMP14 is an up-stream regulator for MMP2 and TIMP2 expression
  • MIR17 targets TIMP1 and TIMP2 to modulate cardiac matrix remodeling
  • EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration
  • cell & other
    REGULATION
    Other activation of proMMP2 (for normal development)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in thymoma with poor prognosis
    tumoral     --low  
    by aberrant hypermethylation in cervical carcinoma
    tumoral     --over  
    in esophageal squamous cell carcinoma
    tumoral       loss of function
    in Hodgkin and Reed-Sternberg cells
    constitutional     --over  
    in the synovium and cartilage of osteoarthritis
    tumoral     --over  
    is associated with accumulation of the pleural effusion in malignancy
    Susceptibility
    Variant & Polymorphism
    Candidate gene determination of TIMP2 in pleural fluid may contribute to differentiate tuberculous pleurisy (TP) from malignat pleurisy (MP)
    Marker
  • TIMP2 and MMP9 expression had a synergistic role as efficient prognostic indicators for CRC patients
  • Therapy target
    ANIMAL & CELL MODELS