MMP1

MMP1, also known as MMP-1, contains 4 hemopexin-like domains and is a member of the matrix metalloproteinase (MMP) family. Matrix metalloproteases, also called matrixins, are zinc-dependent endopeptidases that are the major proteases involved in ECM degradation. MMPs are capable of degrading a wide range of extracellular molecules and a number of bioactive molecules. MMP activity is regulated by two major endogenous inhibitors: alpha2-macroglobulin and tissue inhibitors of metalloproteases (TIMPs). MMPs play a central role in cell proliferation, migration, differentiation, angiogenesis, apoptosis and host defences. Dysregulatoin of MMPs has been implicated in many diseases including arthritis, chronic ulcers, encephalomyelitis and cancer. Tumour metastasis is a multistep process involving the dessemination of tumor cells from the primary tumor to secondarys at a distant organ or tissue. One of the first steps in metastasis is the degradation of the basement membrane, a process in which MMPs have been implicated. MMPs are secreted by tumor cells themselves or by surrounding stromal cells stimulated by the nearby tumor. Numerous studies have linked altered MMP expression in different human cancers with poor disease prognosis. MMP-1, -2, -3, -7, -9, -13 and -14 all have elevated expression in primary tumors and/or metastases. MMP-1 cleaves collagens of types I, II, and III at one site in the helical domain. It also cleaves collagens of types VII and X. In case of HIV infection, MMP1 interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.

MMP1 Related Areas

Enzyme>>Protease & Regulator>>Metalloprotease & Regulator>>Matrix Metalloproteinase>>MMP-1/MMP1

Cancer>>Angiogenesis>>Matrix Metalloproteinase>>MMP-1/MMP1

MMP1 Alternative Names

MMP1 , CLG, CLGN [Homo sapiens]

Mmp1, Clg, MMP-13, Mmp13 [Mus musculus]

Summaries for MMP1

Entrez Gene summary for MMP1:

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. MMP1 gene encodes a secreted enzyme which breaks down the interstitial collagens, types I, II, and III. MMP1 gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

OMIM - description for MMP1:

Matrix metalloproteinases are zinc-dependent proteases that degrade extracellular matrix proteins. MMP1 is also known as collagenase.

Wikipedia summary for MMP1:

Interstitial collagenase also known as matrix metalloproteinase-1 (MMP1) and fibroblast collagenase is an enzyme that in humans is encoded by the MMP1 gene. Human Fibroblast Collagenase (MMP1) was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA.

Human MMP1 Protein General Information

 

• Protein names: Matrix metalloproteinase-1, Short name=MMP-1
• Sequence length: 469 AA.
• Domain: There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity and in binding TIMP (tissue inhibitor of metalloproteinases). The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
• Sequence similarities: Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.
• Post-translational modification: Undergoes autolytic cleavage to two major forms (22 kDa and 27 kDa). A minor form (25 kDa) is the glycosylated form of the 22 kDa form. The 27 kDa form has no activity while the 22/25 kDa form can act as activator for collagenase.
• Cofactor: Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit.
• Subunit structure: Interacts with HIV-1 Tat.
• Subcellular location: Secreted › extracellular space › extracellular matrix
• Catalytic activity: Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N-terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1' is a hydrophobic residue.
• Enzyme regulation: Can be activated without removal of the activation peptide.

General information above from UniProt

Function for MMP1 Protein

UniProtKB:

MMP1 cleaves collagens of types I, II, and III at one site in the helical domain. MMP1 also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, MMP1 leads to a decrease in neuronal Tat's mediated neurotoxicity.

Genatlas:

• MMP1 is the regulator of extracellular matrix remodeling
• MMP1 has the ability to cleave collagens I, II, III. MMP1 cleaves preferentially the type I collagen
• biological effects of MMP1: keratinocyte migration and reepithelialization, cell migration, platelet aggregation, increased bioavailability of IGF1 and cell, proinflammatory, antiinflammatory
• MMP1 cleaves F2R at the proper site for receptor activation

Homology for human MMP1

• homolog to rattus Mmp1a (58.32 pc)
• homolog to murine Mmp1a (59.32 pc)

Phenotype Information for MMP1

• Gene/Locus: MMP1, CLG
• Phenotype: COPD, rate of decline of lung function in
  {Epidermolysis bullosa dystrophica, autosomal recessive, modifier of}

Phenotype Information for MMP1 from OMIM (Online Mendelian Inheritance in Man)

Drugs for MMP1

Target	Drug Name	Disease	Drug Status
MMP1	BMS 275291	Non-small Cell Lung Cancer, Hormone-refractory Prostate Cancer, Kaposi's Sarcoma	Discontinued in Phase III
MMP1	Prinomastat	Brain Cancer	Discontinued in Phase III
MMP1	Prinomastat	Lung Cancer, Prostate Cancer	Trial halted
MMP1	Marimastat	Pancreatic Cancer, Lung Cancer	Discontinued in Phase III
MMP1	BB-3644	Cancer/Tumors	Discontinued in Phase I
MMP1	XL784	Diabetic nephropathy	Discontinued in Phase II
MMP1	Batimastat	Cancers	Discontinued in Phase I

Drugs for MMP1 from TTD (Therapeutic Targets Database)