Human Gene MMP9 (ENST00000372330.3_4) from GENCODE V47lift37
  Description: matrix metallopeptidase 9 (from RefSeq NM_004994.3)
Gencode Transcript: ENST00000372330.3_4
Gencode Gene: ENSG00000100985.7_5
Transcript (Including UTRs)
   Position: hg19 chr20:44,637,547-44,645,200 Size: 7,654 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr20:44,637,566-44,645,007 Size: 7,442 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:44,637,547-44,645,200)mRNA (may differ from genome)Protein (707 aa)
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-  Comments and Description Text from UniProtKB
  ID: MMP9_HUMAN
DESCRIPTION: RecName: Full=Matrix metalloproteinase-9; Short=MMP-9; EC=3.4.24.35; AltName: Full=92 kDa gelatinase; AltName: Full=92 kDa type IV collagenase; AltName: Full=Gelatinase B; Short=GELB; Contains: RecName: Full=67 kDa matrix metalloproteinase-9; Contains: RecName: Full=82 kDa matrix metalloproteinase-9; Flags: Precursor;
FUNCTION: May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
CATALYTIC ACTIVITY: Cleavage of gelatin types I and V and collagen types IV and V.
COFACTOR: Binds 2 zinc ions per subunit.
COFACTOR: Binds 3 calcium ions per subunit.
ENZYME REGULATION: Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1.
SUBUNIT: Exists as monomer or homodimer; disulfide-linked. Exists also as heterodimer with a 25 kDa protein. Macrophages and transformed cell lines produce only the monomeric form. Interacts with ECM1.
INTERACTION: Q8IX30:SCUBE3; NbExp=2; IntAct=EBI-1382326, EBI-4479975;
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (Probable).
TISSUE SPECIFICITY: Produced by normal alveolar macrophages and granulocytes.
INDUCTION: Activated by 4-aminophenylmercuric acetate and phorbol ester. Up-regulated by ARHGEF4, SPATA13 and APC via the JNK signaling pathway in colorectal tumor cells.
DOMAIN: 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.
PTM: Processing of the precursor yields different active forms of 64, 67 and 82 kDa. Sequentially processing by MMP3 yields the 82 kDa matrix metalloproteinase-9.
PTM: N- and O-glycosylated.
DISEASE: Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.
DISEASE: Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:613073]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
MISCELLANEOUS: In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.
SIMILARITY: Belongs to the peptidase M10A family.
SIMILARITY: Contains 3 fibronectin type-II domains.
SIMILARITY: Contains 4 hemopexin-like domains.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MMP9ID41408ch20q11.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp9/";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/mmp9/";

-  Primer design for this transcript
 

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Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MMP9
Diseases sorted by gene-association score: metaphyseal anadysplasia 2* (619), metaphyseal anadysplasia* (268), eosinophilic meningitis (23), middle ear squamous cell carcinoma (23), angiostrongyliasis (23), villonodular synovitis (22), internal hemorrhoid (22), central nervous system tuberculosis (22), adamantinous craniopharyngioma (21), atherosclerosis (21), hemorrhoid (21), abdominal aortic aneurysm (20), carotid stenosis (20), pneumococcal meningitis (18), pulmonary emphysema (17), klatskin's tumor (16), cryptogenic organizing pneumonia (15), nasal cavity squamous cell carcinoma (15), brain glioblastoma multiforme (15), middle ear carcinoma (15), kawasaki disease (14), arthritis (13), tropical spastic paraparesis (13), odontogenic myxoma (13), corneal ulcer (13), rosacea (13), rheumatoid nodulosis (13), tongue cancer (12), cholesteatoma (11), extracranial arteriovenous malformation (10), diabetic foot ulcers (10), amaurosis fugax (10), vulvar intraepithelial neoplasia (10), parotitis (10), fibrosarcoma (10), carotid artery disease (10), anal fistula (10), blepharitis (10), focal myositis (10), malignant glioma (10), gingival hypertrophy (10), cholesteatoma of middle ear (10), relapsing-remitting multiple sclerosis (10), spinal cord injury (10), arteriovenous malformation (9), back pain (9), chronic venous leg ulcers (9), pigmented villonodular synovitis (9), oral squamous cell carcinoma (9), sick building syndrome (9), primary angle-closure glaucoma (9), pediatric multiple sclerosis (9), lymphocytic colitis (9), brain edema (9), secondary progressive multiple sclerosis (8), vernal keratoconjunctivitis (8), lentigo maligna melanoma (8), salivary gland cancer (8), acute transverse myelitis (8), adenomyosis (8), mandibuloacral dysplasia (8), light chain deposition disease (8), chronic actinic dermatitis (8), cheilitis (8), diverticulitis (8), mycetoma (8), vibratory urticaria (8), chronic meningitis (8), giant cell tumor (8), sorsby fundus dystrophy (7), stomach cancer (7), inguinal hernia (7), lung giant cell carcinoma (7), chromoblastomycosis (7), colorectal cancer (7), oral cancer (7), periodontal disease (7), bacterial meningitis (7), acute myocardial infarction (7), severe pre-eclampsia (7), h. pylori infection (7), transverse myelitis (7), keratitis (7), hypertensive heart disease (7), chronic follicular conjunctivitis (7), scleritis (7), bronchiolitis obliterans (7), breast adenocarcinoma (6), gingivitis (6), aortic aneurysm (6), intervertebral disc disease (6), appendicitis (6), auditory system cancer (6), primary progressive multiple sclerosis (6), moyamoya disease (6), periodontitis (6), ischemic colitis (6), angiokeratoma circumscriptum (6), psammomatous meningioma (6), villous adenocarcinoma (6), spastic entropion (6), intratubular embryonal carcinoma (6), meningitis (6), chorioamnionitis (6), microvascular complications of diabetes 1 (6), photokeratitis (6), alternating hemiplegia of childhood (6), pneumothorax (6), demyelinating disease (6), takayasu arteritis (6), squamous cell carcinoma, head and neck (5), lyme disease (5), pelvic inflammatory disease (5), skin melanoma (5), keratocystic odontogenic tumor (5), tuberculous meningitis (5), pyoderma (5), senile ectropion (5), lung cancer (5), blepharochalasis (5), bone cancer (5), tonsil squamous cell carcinoma (5), aortic disease (5), glioma (5), periodontosis (5), adult astrocytic tumour (4), ovarian cancer, somatic (4), conjunctival nevus (4), periapical periodontitis (4), pulmonary fibrosis (4), hypercementosis (4), cardiomyopathy, dilated, 1d (4), microcystic meningioma (4), asthma (4), lung disease (4), prostate cancer (3), vascular disease (3), hepatocellular carcinoma (3), gliosarcoma (3), fundus dystrophy (3), cerebrovascular disease (3), urinary bladder cancer (3), interstitial lung disease (3), breast cancer (3), pancreatic cancer (3), arteriosclerosis (3), multiple sclerosis, disease progression, modifier of (3), artery disease (2), obesity (2), esophageal cancer (2), osteosarcoma, somatic (2), emery-dreifuss muscular dystrophy (2), renal cell carcinoma (2), pulmonary fibrosis, idiopathic (2), lung cancer susceptibility 3 (2), myocardial infarction (2), malaria (2), bladder cancer, somatic (1), gastrointestinal system cancer (1), dilated cardiomyopathy (1), tooth agenesis (1), reproductive organ cancer (1), respiratory system disease (1), macular degeneration, age-related, 1 (1), tetralogy of fallot (1), cell type cancer (1), female reproductive organ cancer (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 277.96 RPKM in Whole Blood
Total median expression: 392.38 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR 0.00190.000 Picture PostScript Text
3' UTR -71.90193-0.373 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000562 - FN_type2_col-bd
IPR000585 - Hemopexin/matrixin
IPR018486 - Hemopexin/matrixin_CS
IPR018487 - Hemopexin/matrixin_repeat
IPR013806 - Kringle-like
IPR024079 - MetalloPept_cat_dom
IPR001818 - Pept_M10_metallopeptidase
IPR021190 - Pept_M10A_matrixin
IPR021158 - Pept_M10A_Zn_BS
IPR006026 - Peptidase_Metallo
IPR002477 - Peptidoglycan-bd-like
IPR006970 - PT

Pfam Domains:
PF00040 - Fibronectin type II domain
PF00045 - Hemopexin
PF00413 - Matrixin
PF01471 - Putative peptidoglycan binding domain

SCOP Domains:
47090 - PGBD-like
50923 - Hemopexin-like domain
55486 - Metalloproteases ("zincins"), catalytic domain
57440 - Kringle-like
57535 - Complement control module/SCR domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1GKC - X-ray MuPIT 1GKD - X-ray MuPIT 1ITV - X-ray MuPIT 1L6J - X-ray MuPIT 1LKG - Model 2OVX - X-ray MuPIT 2OVZ - X-ray MuPIT 2OW0 - X-ray MuPIT 2OW1 - X-ray MuPIT 2OW2 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P14780
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004222 metalloendopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001934 positive regulation of protein phosphorylation
GO:0006508 proteolysis
GO:0007566 embryo implantation
GO:0019221 cytokine-mediated signaling pathway
GO:0022617 extracellular matrix disassembly
GO:0030198 extracellular matrix organization
GO:0030225 macrophage differentiation
GO:0030335 positive regulation of cell migration
GO:0030574 collagen catabolic process
GO:0034614 cellular response to reactive oxygen species
GO:0035987 endodermal cell differentiation
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043312 neutrophil degranulation
GO:0043388 positive regulation of DNA binding
GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0050900 leukocyte migration
GO:0051549 positive regulation of keratinocyte migration
GO:0071276 cellular response to cadmium ion
GO:0090200 positive regulation of release of cytochrome c from mitochondria
GO:1900122 positive regulation of receptor binding
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
GO:2001258 negative regulation of cation channel activity
GO:2001268 negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0031012 extracellular matrix
GO:0070062 extracellular exosome
GO:1904724 tertiary granule lumen
GO:1904813 ficolin-1-rich granule lumen


-  Descriptions from all associated GenBank mRNAs
  AK311648 - Homo sapiens cDNA, FLJ18690.
AK313137 - Homo sapiens cDNA, FLJ93627, highly similar to Homo sapiens matrix metalloproteinase 9 (gelatinase B, 92kDagelatinase, 92kDa type IV collagenase) (MMP9), mRNA.
AK301446 - Homo sapiens cDNA FLJ51120 complete cds, highly similar to Matrix metalloproteinase-9 precursor (EC 3.4.24.35).
AK298246 - Homo sapiens cDNA FLJ51036 complete cds, highly similar to Matrix metalloproteinase-9 precursor (EC3.4.24.35).
AK316145 - Homo sapiens cDNA, FLJ79044 complete cds, highly similar to Matrix metalloproteinase-9 precursor (EC 3.4.24.35).
J05070 - Human type IV collagenase mRNA, complete cds.
JA482256 - Sequence 239 from Patent WO2011072091.
JE980548 - Sequence 239 from Patent EP2862929.
LP896223 - Sequence 1087 from Patent EP3253886.
AK303080 - Homo sapiens cDNA FLJ51166 complete cds, highly similar to Matrix metalloproteinase-9 precursor (EC 3.4.24.35).
JD260930 - Sequence 241954 from Patent EP1572962.
BC006093 - Homo sapiens matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase), mRNA (cDNA clone MGC:12688 IMAGE:4054882), complete cds.
DQ896791 - Synthetic construct Homo sapiens clone IMAGE:100011251; FLH199419.01L; RZPDo839F0981D matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) (MMP9) gene, encodes complete protein.
EU176415 - Synthetic construct Homo sapiens clone IMAGE:100006537; FLH197205.01X; RZPDo839E05252D matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) (MMP9) gene, encodes complete protein.
AB528343 - Synthetic construct DNA, clone: pF1KB9974, Homo sapiens MMP9 gene for matrix metallopeptidase 9, without stop codon, in Flexi system.
CU675241 - Synthetic construct Homo sapiens gateway clone IMAGE:100020714 5' read MMP9 mRNA.
KJ897197 - Synthetic construct Homo sapiens clone ccsbBroadEn_06591 MMP9 gene, encodes complete protein.
AK302530 - Homo sapiens cDNA FLJ52524 complete cds, moderately similar to Matrix metalloproteinase-9 precursor (EC3.4.24.35).
HQ874462 - Homo sapiens matrix metalloproteinase-9 mRNA, partial cds.
JD255046 - Sequence 236070 from Patent EP1572962.
JD123490 - Sequence 104514 from Patent EP1572962.
JD135087 - Sequence 116111 from Patent EP1572962.
JD458880 - Sequence 439904 from Patent EP1572962.
JD500877 - Sequence 481901 from Patent EP1572962.
JD541093 - Sequence 522117 from Patent EP1572962.
JD205917 - Sequence 186941 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_reckPathway - Inhibition of Matrix Metalloproteinases

Reactome (by CSHL, EBI, and GO)

Protein P14780 (Reactome details) participates in the following event(s):

R-HSA-1604690 Activation of MMP9 intermediate form by MMPs
R-HSA-1604722 Activation of proMMP9 by proteases
R-HSA-1592436 Initial activation of proMMP9 by MMPs
R-HSA-1602454 proMMP9 binds TIMP1
R-HSA-1454791 MMP2, MMP7, MMP9 bind CD44
R-HSA-6798745 Exocytosis of tertiary granule lumen proteins
R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-1454781 MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin
R-HSA-2168982 Collagen type XVI degradation by MMP9
R-NUL-2484927 Collagen type XVI degradation
R-HSA-1433374 Processing of SCF isoform 1
R-HSA-1564142 Collagen type IV degradation by MMP2,3,4,9,10,12
R-HSA-1474213 Collagen type III degradation by MMP1,8,9,13
R-HSA-1564164 Collagen type V degradation by MMP2,9,10
R-HSA-1564112 Collagen type VI degradation by MMP2,9,11
R-HSA-1564179 Collagen type XI degradation by MMP1,2,3,9
R-NUL-2484859 Collagen type XI degradation by MMP1,2,3,9
R-HSA-1564117 Collagen type XIV degradation by MMP9,13
R-NUL-2484948 Collagen XIV degradation
R-HSA-2168923 Collagen type XVIII endostatin release
R-HSA-2485148 Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13
R-HSA-1566962 Elastin degradation by elastin-degrading extracellular proteinases
R-HSA-1592270 NID1 degradation by MMP1, 9, 12, ELANE
R-NUL-2533972 Nid1 degradation by MMP1, 9, 12, ELANE
R-HSA-3791295 Aggrecan degradation by MMP1,2,3,7,9,12,13
R-NUL-3814821 Aggrecan degradation by MMP1,2,3,7,9,12,13
R-HSA-3827958 E-cadherin degradation by MMP9, KLK7
R-HSA-8943959 MMP2, MMP9 cleave SCUBE3
R-HSA-2213200 Release of endostatin-like peptides
R-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-6798695 Neutrophil degranulation
R-HSA-1442490 Collagen degradation
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1474244 Extracellular matrix organization
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-449147 Signaling by Interleukins
R-HSA-168249 Innate Immune System
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168256 Immune System
R-HSA-1474290 Collagen formation
R-HSA-162582 Signal Transduction
R-HSA-422475 Axon guidance
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B2R7V9, CLG4B, ENST00000372330.1, ENST00000372330.2, MMP9_HUMAN, NM_004994, P14780, Q3LR70, Q8N725, Q9H4Z1, Q9UCJ9, Q9UCL1, Q9UDK2, uc318jvf.1, uc318jvf.2
UCSC ID: ENST00000372330.3_4
RefSeq Accession: NM_004994.3
Protein: P14780 (aka MMP9_HUMAN or MM09_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.