MMP9

Protein identityUniProt · HPA

UniProt accession

P14780

Gene

MMP9

Ensembl

ENSG00000100985

Chromosome

20

Canonical length

707 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted secreted proteins

Subcellular location

Cytosol

Secretome location

Secreted to blood

Quaternary structure

Homodimer

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. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

707 residues, UniProt reviewed canonical sequence.

>P14780|MMP9
     1  MSLWQPLVLV LLVLGCCFAA PRQRQSTLVL FPGDLRTNLT DRQLAEEYLY RYGYTRVAEM
    61  RGESKSLGPA LLLLQKQLSL PETGELDSAT LKAMRTPRCG VPDLGRFQTF EGDLKWHHHN
   121  ITYWIQNYSE DLPRAVIDDA FARAFALWSA VTPLTFTRVY SRDADIVIQF GVAEHGDGYP
   181  FDGKDGLLAH AFPPGPGIQG DAHFDDDELW SLGKGVVVPT RFGNADGAAC HFPFIFEGRS
   241  YSACTTDGRS DGLPWCSTTA NYDTDDRFGF CPSERLYTQD GNADGKPCQF PFIFQGQSYS
   301  ACTTDGRSDG YRWCATTANY DRDKLFGFCP TRADSTVMGG NSAGELCVFP FTFLGKEYST
   361  CTSEGRGDGR LWCATTSNFD SDKKWGFCPD QGYSLFLVAA HEFGHALGLD HSSVPEALMY
   421  PMYRFTEGPP LHKDDVNGIR HLYGPRPEPE PRPPTTTTPQ PTAPPTVCPT GPPTVHPSER
   481  PTAGPTGPPS AGPTGPPTAG PSTATTVPLS PVDDACNVNI FDAIAEIGNQ LYLFKDGKYW
   541  RFSEGRGSRP QGPFLIADKW PALPRKLDSV FEERLSKKLF FFSGRQVWVY TGASVLGPRR
   601  LDKLGLGADV AQVTGALRSG RGKMLLFSGR RLWRFDVKAQ MVDPRSASEV DRMFPGVPLD
   661  THDVFQYREK AYFCQDRFYW RVSSRSELNQ VDQVGYVTYD ILQCPED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MMP9 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

356 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MMP9.

Disease | AllUniProt

Conditions MMP9 is implicated in, by any mechanism.

• Intervertebral disc disease (IDD) MIM:603932
• Metaphyseal anadysplasia 2 (MANDP2) MIM:613073

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 507 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Metaphyseal anadysplasia 2

Disease | ImmuneIEDB

Conditions an epitope on MMP9 was assayed in.

• colonic benign neoplasm T cell

ReferencesPubMed · IEDB

Publications for MMP9 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

1.21

gnomAD pLI

0

gnomAD missense Z

0.41

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• cell migration
• cellular response to lipopolysaccharide
• cellular response to UV-A
• collagen catabolic process
• embryo implantation
• endodermal cell differentiation
• ephrin receptor signaling pathway
• extracellular matrix disassembly
• extracellular matrix organization
• macrophage differentiation
• negative regulation of apoptotic process
• negative regulation of intrinsic apoptotic signaling pathway
• positive regulation of apoptotic process
• positive regulation of DNA binding
• positive regulation of epidermal growth factor receptor signaling pathway
• positive regulation of keratinocyte migration
• positive regulation of protein phosphorylation
• positive regulation of release of cytochrome c from mitochondria
• positive regulation of vascular associated smooth muscle cell proliferation
• proteolysis
• regulation of neuroinflammatory response
• response to amyloid-beta
• skeletal system development
• negative regulation of cation transmembrane transport
• negative regulation of epithelial cell differentiation involved in kidney development

Molecular functions

• collagen binding
• endopeptidase activity
• identical protein binding
• metalloendopeptidase activity
• metallopeptidase activity
• peptidase activity
• serine-type endopeptidase activity
• zinc ion binding

Cellular components

• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• tertiary granule lumen

Protein domainsUniProt · Pfam · InterPro

• Fibronectin type II domain
• Hemopexin-like domain
• Peptidase M10, metallopeptidase
• Peptidase, metallopeptidase
• Kringle-like fold
• Hemopexin, conserved site
• Hemopexin-like repeats
• Peptidase M10A, cysteine switch, zinc binding site
• Peptidase M10A
• Metallopeptidase, catalytic domain superfamily
• Peptidase M10A, catalytic domain
• PGBD-like superfamily
• Hemopexin-like domain superfamily
• Fibronectin type II domain superfamily
• Fibronectin type II domain
• Hemopexin
• Matrixin

KeywordsUniProt

• Calcium
• Collagen degradation
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hydrolase
• Metal-binding
• Metalloprotease
• Protease
• Repeat
• Secreted
• Signal
• Zinc
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of MMP9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ECM1
• RECK