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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
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