Reviewed, UniProtKB/Swiss-Prot P14780 (MMP9_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	707 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular space › extracellular 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.

Ontologies

Keywords
Biological process	Collagen degradation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW macrophage differentiation Traceable author statement. Source: UniProtKB proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: UniProtKB proteinaceous extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW collagen binding Traceable author statement. Source: UniProtKB metalloendopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB zinc ion binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Propeptide

20 – 93

74

Activation peptide

PRO_0000028754

Chain

94 – ?

67 kDa matrix metalloproteinase-9

PRO_0000028755

Chain

107 – 707

601

82 kDa matrix metalloproteinase-9

PRO_0000028756

Propeptide

? – 707

Removed in 64 kDa matrix metalloproteinase-9 and 67 kDa matrix metalloproteinase-9

PRO_0000028757

Regions

Domain

225 – 273

49

Fibronectin type-II 1

Domain

283 – 331

49

Fibronectin type-II 2

Domain

342 – 390

49

Fibronectin type-II 3

Domain

521 – 565

45

Hemopexin-like 1

Domain

567 – 608

42

Hemopexin-like 2

Domain

613 – 659

47

Hemopexin-like 3

Domain

661 – 704

44

Hemopexin-like 4

Motif

97 – 104

8

Cysteine switch By similarity

Sites

Active site

402

1

Metal binding

99

1

Zinc 2; in inhibited form

Metal binding

131

1

Calcium 1

Metal binding

165

1

Calcium 2; via carbonyl oxygen

Metal binding

175

1

Zinc 1; structural

Metal binding

177

1

Zinc 1; structural

Metal binding

182

1

Calcium 3

Metal binding

183

1

Calcium 3; via carbonyl oxygen

Metal binding

185

1

Calcium 3; via carbonyl oxygen

Metal binding

187

1

Calcium 3; via carbonyl oxygen

Metal binding

190

1

Zinc 1; structural

Metal binding

197

1

Calcium 2; via carbonyl oxygen

Metal binding

199

1

Calcium 2; via carbonyl oxygen

Metal binding

201

1

Calcium 2

Metal binding

203

1

Zinc 1; structural

Metal binding

205

1

Calcium 3

Metal binding

206

1

Calcium 1

Metal binding

208

1

Calcium 1

Metal binding

208

1

Calcium 3

Metal binding

401

1

Zinc 2; catalytic

Metal binding

405

1

Zinc 2; catalytic

Metal binding

411

1

Zinc 2; catalytic

Site

59 – 60

2

Cleavage; by MMP3

Site

106 – 107

2

Cleavage; by MMP3

Amino acid modifications

Glycosylation

38

1

N-linked (GlcNAc...) Potential

Glycosylation

120

1

N-linked (GlcNAc...) Potential

Glycosylation

127

1

N-linked (GlcNAc...) Potential

Disulfide bond

230 ↔ 256

By similarity

Disulfide bond

244 ↔ 271

By similarity

Disulfide bond

288 ↔ 314

By similarity

Disulfide bond

302 ↔ 329

By similarity

Disulfide bond

347 ↔ 373

By similarity

Disulfide bond

361 ↔ 388

By similarity

Disulfide bond

516 ↔ 704

Natural variations

Natural variant

20

1

A → V: dbSNP rs1805088.

VAR_013780

Natural variant

38

1

N → S: dbSNP rs41427445.

VAR_037004

Natural variant

82

1

E → K: dbSNP rs1805089.

VAR_013781

Natural variant

127

1

N → K: dbSNP rs3918252.

VAR_020054

Natural variant

239

1

R → H: dbSNP rs28763886.

VAR_025165

Natural variant

279

1

Q → R Common polymorphism; may be associated with susceptibility to LDH. dbSNP rs17576.

VAR_013782

Natural variant

571

1

F → V: dbSNP rs35691798.

VAR_025166

Natural variant

574

1

P → R: dbSNP rs2250889.

VAR_024595

Natural variant

668

1

R → Q: dbSNP rs17577.

VAR_014742

Secondary structure

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707

Helix Strand Turn

Details...

Helix

41 – 51

11

Helix

68 – 78

11

Helix

88 – 94

7

Beta strand

103 – 105

3

Beta strand

119 – 125

7

Beta strand

130 – 132

3

Helix

134 – 149

16

Beta strand

151 – 153

3

Beta strand

155 – 158

4

Beta strand

164 – 171

8

Beta strand

176 – 178

3

Beta strand

183 – 186

4

Beta strand

189 – 191

3

Beta strand

194 – 196

3

Turn

197 – 200

4

Beta strand

202 – 205

4

Beta strand

213 – 219

7

Helix

220 – 231

12

Beta strand

245 – 247

3