MMP14

Target id: 1638

Nomenclature: MMP14

Family: M10: Matrix metallopeptidase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     MMP14 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 582 14q11-q12 MMP14 matrix metallopeptidase 14
Mouse - 582 14 C2 Mmp14 matrix metallopeptidase 14 (membrane-inserted)
Rat - 582 15p13 Mmp14 matrix metallopeptidase 14
Previous and Unofficial Names
MMP- X1 | membrane type 1 metalloprotease | membrane-type matrix metalloproteinase 1 | MT1MMP | MTMMP1 | Membrane type 1-MMP | matrix metallopeptidase 14 (membrane-inserted)
Database Links
Specialist databases
MEROPS M10.014 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.24.80

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 29e [PMID: 23631440] Hs Inhibition 8.4 pKi 2
pKi 8.4 (Ki 4x10-9 M) [2]
ilomastat Hs Inhibition 7.6 pIC50 4
pIC50 7.6 (IC50 2.3x10-8 M) [4]
CGS-27023A Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.3x10-8 M) [5]
Immunopharmacology Comments
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [1], has shown preclinical efficacy in the mouse collagen-induced arthritis (CIA) model of RA [3]. DX-2400 inhibits MMP14 activity with a Ki of 0.8 nM [1].
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
click arrow to show/hide IEA associations
GO:1905523 positive regulation of macrophage migration IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0045579 positive regulation of B cell differentiation ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1905523 positive regulation of macrophage migration IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1905523 positive regulation of macrophage migration IEA
Immuno Disease Associations
Disease Name:  Rheumatoid arthritis
Disease Synonyms:  no synonynms
Comment:  MMP14 (also called MT1-MMP) is highly expressed in fibroblast-like synoviocytes and macrophages from patients with RA, and is reckoned to be one of the main MMPs involved in degradation of collagenous cartilage matrix
Disease X-refs:  Disease Ontology: DOID:7148
OMIM: 180300
References:  6-7
Clinically-Relevant Mutations and Pathophysiology
Disease:  Multicentric osteolysis, nodulosis, and arthropathy
Synonyms: Nodulosis-arthropathy-osteolysis syndrome [Orphanet: ORPHA85196]
OMIM: 259600
Orphanet: ORPHA85196
Disease:  Winchester syndrome
OMIM: 277950
Orphanet: ORPHA3460

References

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1. Devy L, Huang L, Naa L, Yanamandra N, Pieters H, Frans N, Chang E, Tao Q, Vanhove M, Lejeune A et al.. (2009) Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res., 69 (4): 1517-26. [PMID:19208838]

2. Jin Y, Roycik MD, Bosco DB, Cao Q, Constantino MH, Schwartz MA, Sang QX. (2013) Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core. J. Med. Chem., 56 (11): 4357-73. [PMID:23631440]

3. Kaneko K, Williams RO, Dransfield DT, Nixon AE, Sandison A, Itoh Y. (2016) Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis Factor Blockade. Arthritis Rheumatol, 68 (2): 521-31. [PMID:26315469]

4. Ma D, Wu W, Yang G, Li J, Li J, Ye Q. (2004) Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors. Bioorg. Med. Chem. Lett., 14 (1): 47-50. [PMID:14684295]

5. Nuti E, Casalini F, Santamaria S, Gabelloni P, Bendinelli S, Da Pozzo E, Costa B, Marinelli L, La Pietra V, Novellino E et al.. (2011) Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors. Eur J Med Chem, 46 (7): 2617-29. [PMID:21514700]

6. Pap T, Shigeyama Y, Kuchen S, Fernihough JK, Simmen B, Gay RE, Billingham M, Gay S. (2000) Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Arthritis Rheum., 43 (6): 1226-32. [PMID:10857781]

7. Sabeh F, Fox D, Weiss SJ. (2010) Membrane-type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function. J. Immunol., 184 (11): 6396-406. [PMID:20483788]

How to cite this page

M10: Matrix metallopeptidase: MMP14. Last modified on 06/04/2018. Accessed on 21/06/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1638.