MMP14

Protein identityUniProt · HPA

UniProt accession

P50281

Gene

MMP14

Ensembl

ENSG00000157227

Chromosome

14

Canonical length

582 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Intermediate filaments,Cytosol

OverviewNCBI Gene

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. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

582 residues, UniProt reviewed canonical sequence.

>P50281|MMP14
     1  MSPAPRPPRC LLLPLLTLGT ALASLGSAQS SSFSPEAWLQ QYGYLPPGDL RTHTQRSPQS
    61  LSAAIAAMQK FYGLQVTGKA DADTMKAMRR PRCGVPDKFG AEIKANVRRK RYAIQGLKWQ
   121  HNEITFCIQN YTPKVGEYAT YEAIRKAFRV WESATPLRFR EVPYAYIREG HEKQADIMIF
   181  FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVRNEDLNG NDIFLVAVHE
   241  LGHALGLEHS SDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGGESGFP TKMPPQPRTT
   301  SRPSVPDKPK NPTYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM DGYPMPIGQF
   361  WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF
   421  WMPNGKTYFF RGNKYYRFNE ELRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG
   481  NKYWKFNNQK LKVEPGYPKS ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGGGAVSAA
   541  AVVLPVLLLL LVLAVGLAVF FFRRHGTPRR LLYCQRSLLD KV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MMP14 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

149 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MMP14.

Disease | AllUniProt

Conditions MMP14 is implicated in, by any mechanism.

• Winchester syndrome (WNCHRS) MIM:277950

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 381 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Winchester syndrome

ReferencesPubMed · IEDB

Publications for MMP14 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.27

gnomAD pLI

1

gnomAD missense Z

1.48

DepMap mean gene effect

0.11

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• astrocyte cell migration
• branching morphogenesis of an epithelial tube
• cell motility
• cellular response to genistein
• chondrocyte proliferation
• collagen catabolic process
• craniofacial suture morphogenesis
• embryonic cranial skeleton morphogenesis
• endochondral ossification
• endodermal cell differentiation
• endothelial cell proliferation
• extracellular matrix disassembly
• extracellular matrix organization
• head development
• lung development
• male gonad development
• negative regulation of focal adhesion assembly
• negative regulation of Notch signaling pathway
• ovarian follicle development
• positive regulation of B cell differentiation
• positive regulation of cell growth
• positive regulation of cell migration
• positive regulation of macrophage migration
• positive regulation of myotube differentiation
• positive regulation of protein processing
• protein catabolic process
• protein processing
• proteolysis
• regulation of protein localization to plasma membrane
• response to estrogen
• response to hypoxia
• response to mechanical stimulus
• response to odorant
• response to oxidative stress
• skeletal system development
• tissue remodeling
• zymogen activation
• negative regulation of GDF15-GFRAL signaling pathway

Molecular functions

• endopeptidase activity
• integrin binding
• metalloaminopeptidase activity
• metalloendopeptidase activity
• serine-type endopeptidase activity
• zinc ion binding

Cellular components

• cytoplasmic vesicle
• cytosol
• extracellular matrix
• extracellular space
• focal adhesion
• Golgi lumen
• intermediate filament cytoskeleton
• macropinosome
• melanosome
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Hemopexin-like domain
• Peptidase M10, metallopeptidase
• Peptidoglycan binding-like
• Peptidase, metallopeptidase
• Hemopexin, conserved site
• Hemopexin-like repeats
• Peptidase M10A, cysteine switch, zinc binding site
• Peptidase M10A
• Peptidase M10A, matrix metallopeptidase, C-terminal
• Metallopeptidase, catalytic domain superfamily
• Peptidase M10A, catalytic domain
• PGBD-like superfamily
• Hemopexin-like domain superfamily
• Hemopexin
• Matrixin
• Putative peptidoglycan binding domain
• Domain of unknown function (DUF3377)
• PGBD superfamily

KeywordsUniProt

• Calcium
• Cell membrane
• Cleavage on pair of basic residues
• Cytoplasm
• Disulfide bond
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Osteoporosis
• Phosphoprotein
• Protease
• Repeat
• Signal
• Transmembrane
• Transmembrane helix
• Zinc
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of MMP14 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BST2
• LAMTOR1
• ADI1
• FGFR4
• FURIN
• TIMP2