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Reviewed, UniProtKB/Swiss-Prot P14780 (MMP9_HUMAN)

Last modified November 25, 2008. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Matrix metalloproteinase-9
      Short name=MMP-9
    EC=3.4.24.35
Alternative name(s):
    92 kDa type IV collagenase
    92 kDa gelatinase
    Gelatinase B
      Short name=GELB
Cleaved into the following 2 chains:
    1- Recommended name:
            67 kDa matrix metalloproteinase-9
    2- Recommended name:
            82 kDa matrix metalloproteinase-9
Gene names
Name: MMP9
Synonyms: CLG4B
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length707 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

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.

Catalytic activity

Cleavage of gelatin types I and V and collagen types IV and V.

Cofactor

Binds 2 zinc ions per subunit.

Binds 3 calcium ions per subunit.

Enzyme regulation

Inhibited by histatin-3 1/24 (histatin-5).

Subunit structure

Exists as monomer, disulfide-linked homodimer, and as a heterodimer with a 25 kDa protein. Macrophages and transformed cell lines produce only the monomeric form.

Subcellular location

Secretedextracellular spaceextracellular matrixProbable.

Tissue specificity

Produced by normal alveolar macrophages and granulocytes.

Induction

Activated by 4-aminophenylmercuric acetate and phorbol ester.

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.

Post-translational modification

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.

Involvement in disease

Defects in MMP9 may be a cause of susceptibility to lumbar disk herniation (LDH) [MIM:603932]. LDH is the predominant cause of low-back pain and unilateral leg pain.

Miscellaneous

In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.

Sequence similarities

Belongs to the peptidase M10A family.

Contains 3 fibronectin type-II domains.

Contains 4 hemopexin-like domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Propeptide20 – 9374Activation peptide
PRO_0000028754
Chain94 – ?67 kDa matrix metalloproteinase-9PRO_0000028755
Chain107 – 70760182 kDa matrix metalloproteinase-9
PRO_0000028756
Propeptide? – 707Removed in 64 kDa matrix metalloproteinase-9 and 67 kDa matrix metalloproteinase-9PRO_0000028757

Regions

Domain225 – 27349Fibronectin type-II 1
Domain283 – 33149Fibronectin type-II 2
Domain342 – 39049Fibronectin type-II 3
Domain521 – 56545Hemopexin-like 1
Domain567 – 60842Hemopexin-like 2
Domain613 – 65947Hemopexin-like 3
Domain661 – 70444Hemopexin-like 4
Motif97 – 1048Cysteine switch By similarity

Sites

Active site4021
Metal binding991Zinc 2; in inhibited form
Metal binding1311Calcium 1
Metal binding1651Calcium 2; via carbonyl oxygen
Metal binding1751Zinc 1; structural
Metal binding1771Zinc 1; structural
Metal binding1821Calcium 3
Metal binding1831Calcium 3; via carbonyl oxygen
Metal binding1851Calcium 3; via carbonyl oxygen
Metal binding1871Calcium 3; via carbonyl oxygen
Metal binding1901Zinc 1; structural
Metal binding1971Calcium 2; via carbonyl oxygen
Metal binding1991Calcium 2; via carbonyl oxygen
Metal binding2011Calcium 2
Metal binding2031Zinc 1; structural
Metal binding2051Calcium 3
Metal binding2061Calcium 1
Metal binding2081Calcium 1
Metal binding2081Calcium 3
Metal binding4011Zinc 2; catalytic
Metal binding4051Zinc 2; catalytic
Metal binding4111Zinc 2; catalytic
Site59 – 602Cleavage; by MMP3
Site106 – 1072Cleavage; by MMP3

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation1201N-linked (GlcNAc...) Potential
Glycosylation1271N-linked (GlcNAc...) Potential
Disulfide bond230 ↔ 256 By similarity
Disulfide bond244 ↔ 271 By similarity
Disulfide bond288 ↔ 314 By similarity
Disulfide bond302 ↔ 329 By similarity
Disulfide bond347 ↔ 373 By similarity
Disulfide bond361 ↔ 388 By similarity
Disulfide bond516 ↔ 704

Natural variations

Natural variant201A → V: dbSNP rs1805088.
VAR_013780
Natural variant381N → S: dbSNP rs41427445.
VAR_037004
Natural variant821E → K: dbSNP rs1805089.
VAR_013781
Natural variant1271N → K: dbSNP rs3918252.
VAR_020054
Natural variant2391R → H: dbSNP rs28763886.
VAR_025165
Natural variant2791Q → R Common polymorphism; may be associated with susceptibility to LDH. dbSNP rs17576.
VAR_013782
Natural variant5711F → V: dbSNP rs35691798.
VAR_025166
Natural variant5741P → R: dbSNP rs2250889.
VAR_024595
Natural variant6681R → Q: dbSNP rs17577.
VAR_014742

Secondary structure

....................................................................................................................... 707
Helix Strand Turn

Details...