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FLASH GENE
Symbol MMP1 contributors: mct/ - updated : 13-06-2015
HGNC name matrix metalloproteinase 1 (interstitial collagenase)
HGNC id 7155
Location 11q22.2      Physical location : 102.660.640 - 102.668.966
Synonym name
  • fibroblast collagenase
  • matrix metallopeptidase 1 (interstitial collagenase)
  • Synonym symbol(s) CLG1I, CLGN, MMP-1, CLG
    EC.number 3.2.24.7
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text member of the MMP cluster
    STRUCTURE 8.33 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   enhancer
    motif Viral sequence   gene pol
    text structure
  • binding sites for ETS family of transcription factors, AP-1, AP-2, Ets/PEA-3
  • DNA methylation contributes to the complexity of the control of MMP1 expression
  • MAPPING cloned Y linked   status confirmed
    Map see DRD2
    Physical map
    ANGPTL5 11q22.2 angiopoietin-like 5 MGC13040 11q22.2 hypothetical protein MGC13040 YAP1 11q13 Yes-associated protein 1, 65kDa LOC120318 11q22.2 similar to 40S ribosomal protein S6 (Phosphoprotein NP33) BIRC3 11q25 baculoviral IAP repeat-containing 3 BIRC2 11q22 baculoviral IAP repeat-containing 2 PORIMIN 11q22.1 Homo sapiens pro-oncosis receptor inducing membrane injury gene (PORIMIN), mRNA. MMP7 11q22.2-q22.3 matrix metalloproteinase 7 (matrilysin, uterine) MMP20 11q22.2-q22.3 matrix metalloproteinase 20 (enamelysin) MMP27 11q24 matrix metalloproteinase 27 MMP8 11q22.2-q22.3 matrix metalloproteinase 8 (neutrophil collagenase) LOC390248 11 similar to matrix metalloproteinase 1 precursor MMP10 11q22.2-q22.3 matrix metalloproteinase 10 (stromelysin 2) MMP1 11q22.2-q22.3 matrix metalloproteinase 1 (interstitial collagenase) LOC120321 11q22.2 similar to casein kinase 1, alpha 1 MMP3 11q22.2-q22.3 matrix metalloproteinase 3 (stromelysin 1, progelatinase) MMP12 11q22.3 matrix metalloproteinase 12 (macrophage elastase) MMP13 11q22.2-q22.3 matrix metalloproteinase 13 (collagenase 3) MGC2714 11q22.2 hypothetical protein MGC2714 DNCH2 11q21-q22.1 dynein, cytoplasmic, heavy polypeptide 2
    regionally located clustering with other MMPs genes
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2081 - 469 - 2003 12730128
    10 - 1903 - 403 - 2003 12730128
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Respiratoryalveolar macrophage Homo sapiens
    cell lineage some tumors cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text umbilical cord at a moderately level
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • secretory segment with a cysteine residue essential for latency and involved in autocatalytic activation
  • a catalytic domain with the zinc-binding site (the cysteine switch)
  • a hinge region and a hemopexin-like C terminal
  • conjugated HemoP , MetalloP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to rattus Mmp1a (58.32 pc)
    homolog to murine Mmp1a (59.32 pc)
    Homologene
    FAMILY
  • peptidase M10A family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • regulator of extracellular matrix remodeling
  • ability to cleave collagens I, II, III, cleaving preferentially the type I collagen
  • biological effects: keratinocyte migration and reepithelialization, cell migration, platelet aggregation, increased bioavailability of IGF1 and cell, proinflammatory, antiinflammatory
  • essential role of MAZ and JUN in up-regulating human MMP1 expression under various inflammatory conditions
  • cleaving F2R at the proper site for receptor activation
  • primary function of MMP1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue
  • emerging new target implicated in oncogenesis and metastasis in diverse cancers
  • plays a key role in the metastatic behavior of melanoma, breast, and prostate cancer cells
  • important mediator of tumorigenesis, inflammation and tissue remodeling through its ability to degrade critical matrix components
  • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS inflammation
    text pro/anti-inflammatory
    PATHWAY
    metabolism
    signaling
    pathway involving EREG and MMP1 that contributes to the formation of early stage breast cancer
    a component
  • MMP1/F2R axis may play a role in neurogenesis following physiological and/or pathological stimuli
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • Ca2+
  • protein
  • binding TIMPs in a 1:1 stoechiometry
  • SP100 interacts with the ETS1 transcription factor, reduces ETS1-DNA binding and inhibits ETS1 transcriptional activity on the MMP1 and PLAU promoters
  • interacting with ETS1 and ERBB2 (having its role for breast cancer in relation with ERBB2 and ETS1)
  • interacting with ADAMTS1 (functional role of MMP1 and ADAMTS1 in promoting osteolytic bone metastasis)
  • is a collagenase and activator of the G protein-coupled protease activated receptor-1 (F2R)
  • TGFA increased proliferation and migration of pancreatic stellate cells (PSCs), and TGFA-induced migration of cells may be partly due to upregulation of MMP1
  • MMP1 agonist is F2R
  • role for ZNF148 in regulation of MMP1 expression, suggesting the possibility of a larger role for ZNF148 in inflammation through interactions with NFKB1
  • cell & other
    REGULATION
    activated by host/tumor cell interaction and mediating the invasive/metastatic behavior of tumor cells through invasion of type I collagen
    proteinases
    plasmin
    repressed by downregulated by TGFB1,retinoic acid,dynamin mediated endocytosis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer and in sporadic colorectal cancer and in squamous cell carcinoma by UV-irradiation
    constitutional     --over  
    in inflammatory bowel disease
    tumoral     --low  
    in diffuse type gastric carcinoma, and in hereditary non-polyposis colorectal carcinoma
    tumoral   LOH    
    in melanomas (invasive and agressive forms)
    Susceptibility
  • to preterm premature rupture of the membrane (PPROM)
  • to higher disease severity in EBDR (epidermolysis bullosa dystrophica)
  • to idiopathic pulmonary fibrosis (IPF)
  • to cutaneous melanoma
  • Variant & Polymorphism SNP , other
  • allele 2G contributing to the risk of PPROM
  • T > C single nucleotide polymorphism found to be protective against PPROM (reduced promoter function)
  • SNP (1G/2G) in the promoter creating a functional ETS binding site resulting in transcriptional upregulation, and increasing teh severity in EBDR
  • polymorphisms of the MMP1 promoter may confer increased risk for IPF
  • associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma
  • Candidate gene for identification of breast lesions that can develop into cancer
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    molecular targeting of MMP1 and ADAMTS1, combined with inhibition of EGFR, may potentially reduce the risk of bone metastasis for a significant number of breast cancer patients
    immunologyinfectious 
    therapeutics that target MMP1-F2R may prove beneficial in the treatment of sepsis
    ANIMAL & CELL MODELS
  • decreased susceptibility to develop lung carcinomas induced by chemical carcinogens in Mmp1a(-/-) mice