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FLASH GENE
Symbol TIMP1 contributors: mct/npt/pgu - updated : 08-07-2015
HGNC name TIMP metallopeptidase inhibitor 1
HGNC id 11820
Location Xp11.23      Physical location : 47.441.689 - 47.446.189
Synonym name
  • tissue inhibitor of metalloproteinase 1 (erythroid potentiating activity, collagenase inhibitor)
  • erythroid potentiating activity
  • fibroblast collagenase inhibitor
    • Synonym symbol(s) EPA, TIMP, TIM, EPO, CLGI, FLJ90373, HCI
    DNA
    TYPE functioning gene
    SPECIAL FEATURE gene in gene, escaping inactivation
    text
  • embedded in intron 5 of SYN1
  • variable retention of the epigenetic silencing mechanisms associated with X inactivation
    • STRUCTURE 4.50 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure binding sites for ETS gene family of transcription factor and for AP1
    MAPPING cloned Y linked Y status confirmed
    Map see SYN1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 931 - 207 - 2009 19513566
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Reproductivefemale systemovary  highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     fibroblast
    cell lineage
    cell lines breast carcinoma
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 12 cysteine residues that form six disulfide bridges
    • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Timp
    Homologene
    FAMILY
  • TIMP family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text binding to the cell surface of MCF-7 breast carcinoma cells and translocating to the nucleus
    basic FUNCTION
  • multifunctional protein, stimulating proliferation of aortic smooth muscle cells and Ras effector pathways
  • erythroid potentiating and cell growth-promoting activities
  • involved in the regulation of bone modeling and remodeling in normal developing human bone
  • inhibits all MMPs, except MMP14
  • reducing tumor growth when it's overexpressed
  • antiapoptotic activity
  • naturally occurring specific inhibitor of matrix metalloproteinases
  • inhibits MMP2 activity, protects against cell death and may be of significance in initiating repair processes and curtailing keratoconus
  • major serum factors that stimulate the induction of TIMP-1 mRNA in quiescent human gingival fibroblasts
  • survival factor of germinal center (GC) B cells functioning as a differentiating and survival factor of GC B cells by modulating CD44 and PTPN6 in the late centrocyte/post-GC stage, regardless of EBV infection
  • significantly inhibited both FAS- and activation-induced cell death of lymphocytes
  • leads to enlarged adipocytes in the state of overnutrition
  • plays an important role in promoting cell growth of breast cancer
  • regulates essential stem cell functions, and may also mediate signaling that affects gene expression and inhibits the growth and differentiation of these cells
  • important role of TIMP1 in protection and recovery from cutaneous photodamage because of its suppression of ECM degradation and inflammation
  • regulates extracellular matrix turnover and also promotes cell growth and has anti-apoptotic activity, which promotes malignant processes in tumor tissue
  • KLK1 and TIMP1 are important in inhibiting vascular smooth muscle cell (VSMC) proliferation and improving vascular remodeling, respectively
    • CELLULAR PROCESS cell life, antiapoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • component with MMP9 (progelatinase B)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding MMPs in a 1:1 stoechiometry
  • activating RAS
  • emerges as a modulator of neuronal outgrowth and morphology in a paracrine and autrocrine manner through the inhibition, at least in part, of MMP2 and not MMP9
  • osteopontin increased TIMP1 secretion by peripheral blood monocytes
  • fine balance between CCNL1 and TIMP1, which may contribute to breast cancer development
  • HAS2 promotes breast cancer cell invasion by suppression of TIMP1
  • colocalizes with CD63 on the surface of mesenchymal stem cells (hMSCs)
  • MMP10 interacting with tissue inhibitors of metalloproteinases TIMP1 and TIMP2
  • MIR17 targets TIMP1 and TIMP2 to modulate cardiac matrix remodeling
    • cell & other
    REGULATION
    activated by SPHK1 (action of SPHK1 on the promoter is through the AP1-response element)
    Other heparin is able to accelerate the hydrolysis of TIMP1 by neutrophil elastase (PMId: 21731773)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in multiple sclerosis, liver fibrosis and left ventricular diastolic dysfunction with hypertension
    tumoral     --over  
    in acute myelogenous leukaemia
    constitutional     --over  
    in scarred keratoconic cornea
    tumoral     --low  
    in high expression of progesterone receptors in breast carcinoma
    tumoral   deletion    
    in colorectal cancer
    tumoral     --over  
    CCNL1 and TIMP1 expression was significantly elevated in breast cancer tissues compared with that in peri-breast cancer tissues
    constitutional     --low  
    in unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts
    constitutional     --over  
    plasma TIMP1 was elevated and correlated with TGFB1 in Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy (CMD), but not in Becker muscular dystrophy
    Susceptibility
    Variant & Polymorphism other demonstrating polymorphic X-chromosome inactivation
    Candidate gene
  • prognostic marker in colorectal and breast cancer
    • Marker
  • relationship between higher plasma levels of TIMP1 and an adverse prognosis in patients with liver metastases, and plasma TIMP1 levels could help the detection of patients with worse outcome
  • biomarker for thyroid cancer exhibiting differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power
    • Therapy target
    ANIMAL & CELL MODELS