P14780 (MMP9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-9
Short name=MMP-9
EC=3.4.24.35

Alternative name(s):
92 kDa gelatinase
92 kDa type IV collagenase
Gelatinase B
Short name=GELB

Cleaved into the following 2 chains:

1. 67 kDa matrix metalloproteinase-9
2. 82 kDa matrix metalloproteinase-9

Gene names

Name:	MMP9
Synonyms:	CLG4B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. 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. Ref.16
Catalytic activity	Cleavage of gelatin types I and V and collagen types IV and V. Ref.16
Cofactor	Binds 2 zinc ions per subunit. Binds 3 calcium ions per subunit.
Enzyme regulation	Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1. Ref.19 Ref.21
Subunit structure	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. Ref.18 Ref.21 Ref.27
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. Ref.11 Ref.12 Ref.19 Ref.21 Ref.24
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. N- and O-glycosylated. Ref.9
Involvement in disease	Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.22 Metaphyseal anadysplasia 2 (MANDP2) [MIM:613073]: A bone development disorder characterized by skeletal anomalies that 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. Note: The disease is caused by mutations affecting the gene represented in this entry.
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	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW embryo implantation Inferred from electronic annotation. Source: Compara extracellular matrix disassembly Traceable author statement. Source: Reactome macrophage differentiation Traceable author statement PubMed 2251898. Source: UniProtKB positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of keratinocyte migration Inferred from mutant phenotype PubMed 17704059. Source: BHF-UCL proteolysis Inferred from direct assay Ref.1. Source: UniProtKB skeletal system development Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from direct assay PubMed 2251898. Source: UniProtKB proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	collagen binding Traceable author statement PubMed 2251898. Source: UniProtKB metalloendopeptidase activity Inferred from direct assay PubMed 16192646Ref.1. Source: UniProtKB zinc ion binding Traceable author statement PubMed 2251898. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SCUBE3	Q8IX30	2	EBI-1382326,EBI-4479975

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

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. Ref.4 Ref.5 Ref.29
Corresponds to variant rs1805088 [ dbSNP | Ensembl ].

VAR_013780

Natural variant

38

1

N → S.
Corresponds to variant rs41427445 [ dbSNP | Ensembl ].

VAR_037004

Natural variant

82

1

E → K. Ref.29
Corresponds to variant rs1805089 [ dbSNP | Ensembl ].

VAR_013781

Natural variant

127

1

N → K. Ref.4
Corresponds to variant rs3918252 [ dbSNP | Ensembl ].

VAR_020054

Natural variant

239

1

R → H. Ref.5
Corresponds to variant rs28763886 [ dbSNP | Ensembl ].

VAR_025165

Natural variant

279

1

Q → R Common polymorphism; may be associated with susceptibility to IDD. Ref.1 Ref.4 Ref.7 Ref.29
Corresponds to variant rs17576 [ dbSNP | Ensembl ].

VAR_013782

Natural variant

571

1

F → V. Ref.5
Corresponds to variant rs35691798 [ dbSNP | Ensembl ].

VAR_025166

Natural variant

574

1

R → P. Ref.1 Ref.3 Ref.4 Ref.5 Ref.7
Corresponds to variant rs2250889 [ dbSNP | Ensembl ].

VAR_024595

Natural variant

668

1

R → Q. Ref.4 Ref.5
Corresponds to variant rs17577 [ dbSNP | Ensembl ].

VAR_014742

Experimental info

Mutagenesis

402

1

E → Q: Loss of activity. Ref.26

Sequence conflict

110

1

F → L in BAG35956. Ref.3

Secondary structure

1

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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 – 215

3

Beta strand

221 – 225

5

Beta strand

232 – 238

7

Beta strand

240 – 243

4

Beta strand

255 – 261

7

Helix

262 – 265

4

Beta strand

268 – 270

3

Turn

274 – 276

3

Beta strand

279 – 283

5

Beta strand

290 – 294

5

Beta strand

297 – 301

5

Beta strand

313 – 319

7

Helix

320 – 323

4

Beta strand

326 – 328

3

Helix

333 – 335

3

Turn

340 – 344

5

Beta strand

349 – 353

5

Beta strand

356 – 358

3

Beta strand

372 – 378

7

Helix

379 – 382

4

Beta strand

385 – 387

3

Beta strand

391 – 394

4

Helix

395 – 406

12

Beta strand

420 – 422

3

Helix

433 – 442

10

Helix

515 – 517

3

Beta strand

522 – 527

6

Beta strand

530 – 535

6

Beta strand

538 – 542

5

Beta strand

545 – 547

3

Beta strand

551 – 555

5

Helix

556 – 559

4

Beta strand

568 – 572

5

Turn

574 – 576

3

Beta strand

579 – 583

5

Beta strand

586 – 591

6

Beta strand

594 – 600

7

Helix

601 – 604

4

Beta strand

615 – 618

4

Beta strand

623 – 628

6

Beta strand

631 – 636

6

Turn

637 – 640

4

Helix

644 – 646

3

Helix

650 – 653

4

Beta strand

662 – 667

6

Beta strand

670 – 675

6

Beta strand

678 – 683

6

Beta strand

690 – 696

7

Turn

697 – 700

4

Sequences

	Sequence		Length	Mass (Da)
	P14780 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 2165AC8CA1466209	FASTA	707	78,458
	10 20 30 40 50 60 MSLWQPLVLV LLVLGCCFAA PRQRQSTLVL FPGDLRTNLT DRQLAEEYLY RYGYTRVAEM 70 80 90 100 110 120 RGESKSLGPA LLLLQKQLSL PETGELDSAT LKAMRTPRCG VPDLGRFQTF EGDLKWHHHN 130 140 150 160 170 180 ITYWIQNYSE DLPRAVIDDA FARAFALWSA VTPLTFTRVY SRDADIVIQF GVAEHGDGYP 190 200 210 220 230 240 FDGKDGLLAH AFPPGPGIQG DAHFDDDELW SLGKGVVVPT RFGNADGAAC HFPFIFEGRS 250 260 270 280 290 300 YSACTTDGRS DGLPWCSTTA NYDTDDRFGF CPSERLYTQD GNADGKPCQF PFIFQGQSYS 310 320 330 340 350 360 ACTTDGRSDG YRWCATTANY DRDKLFGFCP TRADSTVMGG NSAGELCVFP FTFLGKEYST 370 380 390 400 410 420 CTSEGRGDGR LWCATTSNFD SDKKWGFCPD QGYSLFLVAA HEFGHALGLD HSSVPEALMY 430 440 450 460 470 480 PMYRFTEGPP LHKDDVNGIR HLYGPRPEPE PRPPTTTTPQ PTAPPTVCPT GPPTVHPSER 490 500 510 520 530 540 PTAGPTGPPS AGPTGPPTAG PSTATTVPLS PVDDACNVNI FDAIAEIGNQ LYLFKDGKYW 550 560 570 580 590 600 RFSEGRGSRP QGPFLIADKW PALPRKLDSV FEERLSKKLF FFSGRQVWVY TGASVLGPRR 610 620 630 640 650 660 LDKLGLGADV AQVTGALRSG RGKMLLFSGR RLWRFDVKAQ MVDPRSASEV DRMFPGVPLD 670 680 690 700 THDVFQYREK AYFCQDRFYW RVSSRSELNQ VDQVGYVTYD ILQCPED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages." Wilhelm S.M., Collier I.E., Marmer B.L., Eisen A.Z., Grant G.A., Goldberg G.I. J. Biol. Chem. 264:17213-17221(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-37, VARIANTS ARG-279 AND PRO-574.
[2]	"Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells." Huhtala P., Tuuttila A., Chow L.T., Lohi J., Keski-Oja J., Tryggvason K. J. Biol. Chem. 266:16485-16490(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-574. Tissue: Umbilical cord blood.
[4]	SeattleSNPs variation discovery resource Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-20; LYS-127; ARG-279; PRO-574 AND GLN-668.
[5]	NIEHS SNPs program Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-20; HIS-239; VAL-571; PRO-574 AND GLN-668.
[6]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-279 AND PRO-574. Tissue: B-cell.
[8]	"Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells." Sato H., Seiki M. Oncogene 8:395-405(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
[9]	"Human neutrophil gelatinase: a marker for circulating blood neutrophils. Purification and quantitation by enzyme linked immunosorbent assay." Kjeldsen L., Bjerrum O.W., Hovgaard D., Johnsen A.H., Sehested M., Borregaard N. Eur. J. Haematol. 49:180-191(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-39, GLYCOSYLATION. Tissue: Neutrophil.
[10]	"The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers." van Ranst M., Norga K., Masure S., Proost P., Vandekerckhove F., Auwerx J., van Damme J., Opdenakker G. Cytokine 3:231-239(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-37.
[11]	"Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9." Ogata Y., Enghild J.J., Nagase H. J. Biol. Chem. 267:3581-3584(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34; 60-71 AND 107-118, INDUCTION, PROTEOLYTIC PROCESSING BY MMP3.
[12]	"Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties." Okada Y., Gonoji Y., Naka K., Tomita K., Nakanishi I., Iwata K., Yamashita K., Hayakawa T. J. Biol. Chem. 267:21712-21719(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-32 AND 94-111, PROTEOLYTIC PROCESSING, INDUCTION. Tissue: Fibrosarcoma.
[13]	"Proteolytic and non-proteolytic activation of human neutrophil progelatinase B." Sang Q.X., Birkedal-Hansen H., Van Wart H.E. Biochim. Biophys. Acta 1251:99-108(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-27; 60-67; 94-101 AND 107-113.
[14]	"Purification and identification of 91-kDa neutrophil gelatinase. Release by the activating peptide interleukin-8." Masure S., Proost P., van Damme J., Opdenakker G. Eur. J. Biochem. 198:391-398(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-60. Tissue: Neutrophil.
[15]	"Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis." Opdenakker G., Masure S., Grillet B., Van Damme J. Lymphokine Cytokine Res. 10:317-324(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-37.
[16]	"Latent collagenase and gelatinase from human neutrophils and their activation." Tschesche H., Knaeuper V., Kraemer S., Michaelis J., Oberhoff R., Reinke H. Matrix Suppl. 1:245-255(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 93-115, FUNCTION, CATALYTIC ACTIVITY. Tissue: Blood.
[17]	"Purification and characterization of human 92-kDa type IV collagenase (gelatinase B)." Kang K., Lee D.-H. Exp. Mol. Med. 28:161-165(1996) Cited for: CHARACTERIZATION.
[18]	"Characterization of the monomeric and dimeric forms of latent and active matrix metalloproteinase-9. Differential rates for activation by stromelysin 1." Olson M.W., Bernardo M.M., Pietila M., Gervasi D.C., Toth M., Kotra L.P., Massova I., Mobashery S., Fridman R. J. Biol. Chem. 275:2661-2668(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[19]	"Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease." Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F., Oppenheim F.G. Infect. Immun. 69:1402-1408(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[20]	"Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases." Takino T., Koshikawa N., Miyamori H., Tanaka M., Sasaki T., Okada Y., Seiki M., Sato H. Oncogene 22:4617-4626(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF KISS1.
[21]	"Extracellular matrix protein 1 inhibits the activity of matrix metalloproteinase 9 through high-affinity protein/protein interactions." Fujimoto N., Terlizzi J., Aho S., Brittingham R., Fertala A., Oyama N., McGrath J.A., Uitto J. Exp. Dermatol. 15:300-307(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ECM1, ENZYME REGULATION.
[22]	"A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation." Hirose Y., Chiba K., Karasugi T., Nakajima M., Kawaguchi Y., Mikami Y., Furuichi T., Mio F., Miyake A., Miyamoto T., Ozaki K., Takahashi A., Mizuta H., Kubo T., Kimura T., Tanaka T., Toyama Y., Ikegawa S. Am. J. Hum. Genet. 82:1122-1129(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO IDD.
[23]	"Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia." Lausch E., Keppler R., Hilbert K., Cormier-Daire V., Nikkel S., Nishimura G., Unger S., Spranger J., Superti-Furga A., Zabel B. Am. J. Hum. Genet. 85:168-178(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN METAPHYSEAL ANADYSPLASIA TYPE 2.
[24]	"The adenomatous polyposis coli-associated exchange factors Asef and Asef2 are required for adenoma formation in Apc(Min/+)mice." Kawasaki Y., Tsuji S., Muroya K., Furukawa S., Shibata Y., Okuno M., Ohwada S., Akiyama T. EMBO Rep. 10:1355-1362(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[25]	"Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase." Elkins P.A., Ho Y.S., Smith W.W., Janson C.A., D'Alessio K.J., McQueney M.S., Cummings M.D., Romanic A.M. Acta Crystallogr. D 58:1182-1192(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-444 IN COMPLEX WITH ZINC AND MAGNESIUM IONS.
[26]	"Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor." Rowsell S., Hawtin P., Minshull C.A., Jepson H., Brockbank S.M.V., Barratt D.G., Slater A.M., McPheat W.L., Waterson D., Henney A.M., Pauptit R.A. J. Mol. Biol. 319:173-181(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 107-215 IN COMPLEX WITH INHIBITOR; ZINC AND CALCIUM IONS, MUTAGENESIS OF GLU-402.
[27]	"Structural basis of the adaptive molecular recognition by MMP9." Cha H., Kopetzki E., Huber R., Lanzendoerfer M., Brandstetter H. J. Mol. Biol. 320:1065-1079(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 513-707, SUBUNIT.
[28]	"Theoretical model of human type IV collagenase precursor." Mallena S.C., Sagajkar R.D. Submitted (APR-2002) to the PDB data bank Cited for: 3D-STRUCTURE MODELING.
[29]	"Genetic variation at the matrix metalloproteinase-9 locus on chromosome 20q12.2-13.1." Zhang B., Henney A., Eriksson P., Hamsten A., Watkins H., Ye S. Hum. Genet. 105:418-423(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VAL-20; LYS-82 AND ARG-279.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J05070 mRNA. Translation: AAA51539.1.
M68343 Genomic DNA. No translation available.
M68344 Genomic DNA. No translation available.
M68345 Genomic DNA. No translation available.
M68346 Genomic DNA. No translation available.
M68347 Genomic DNA. No translation available.
M68348 Genomic DNA. No translation available.
M68349 Genomic DNA. No translation available.
M68350 Genomic DNA. No translation available.
M68351 Genomic DNA. No translation available.
M68352 Genomic DNA. No translation available.
M68353 Genomic DNA. No translation available.
M68354 Genomic DNA. No translation available.
M68355 Genomic DNA. No translation available.
AK313137 mRNA. Translation: BAG35956.1.
AF538844 Genomic DNA. Translation: AAM97934.1.
DQ194553 Genomic DNA. Translation: ABA03169.1.
AL162458 Genomic DNA. Translation: CAC10459.1.
BC006093 mRNA. Translation: AAH06093.1.
D10051 Genomic DNA. Translation: BAA20967.1.

IPI

IPI00027509.

PIR

A34458.

RefSeq

NP_004985.2. NM_004994.2.

UniGene

Hs.297413.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GKC	X-ray	2.30	A/B	107-443	[»]
1GKD	X-ray	2.10	A/B	107-443	[»]
1ITV	X-ray	1.95	A/B	513-707	[»]
1L6J	X-ray	2.50	A	20-444	[»]
1LKG	model	-	A	1-707	[»]
2OVX	X-ray	2.00	A/B	110-443	[»]
2OVZ	X-ray	2.00	A/B	110-443	[»]
2OW0	X-ray	2.00	A/B	110-443	[»]
2OW1	X-ray	2.20	A/B	110-443	[»]
2OW2	X-ray	2.90	A/B	110-443	[»]

ProteinModelPortal

P14780.

SMR

P14780. Positions 26-707.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29518N.

IntAct

P14780. 3 interactions.

STRING

9606.ENSP00000361405.

Protein family/group databases

MEROPS

M10.004.

PTM databases

GlycoSuiteDB

P14780.

PhosphoSite

P14780.

Polymorphism databases

DMDM

269849668.

Proteomic databases

PaxDb

P14780.

PeptideAtlas

P14780.

PRIDE

P14780.

Protocols and materials databases

DNASU

4318.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372330; ENSP00000361405; ENSG00000100985.

GeneID

4318.

KEGG

hsa:4318.

UCSC

uc002xqz.3. human.

Organism-specific databases

CTD

4318.

GeneCards

GC20P044637.

H-InvDB

HIX0015874.

HGNC

HGNC:7176. MMP9.

HPA

CAB000348.
HPA001238.

MIM

120361. gene.
603932. phenotype.
613073. phenotype.

neXtProt

NX_P14780.

Orphanet

1040. Metaphyseal anadysplasia.

PharmGKB

PA30889.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG328372.

HOVERGEN

HBG052484.

InParanoid

P14780.

KO

K01403.

OMA

EGDLKWH.

OrthoDB

EOG4H9XJZ.

PhylomeDB

P14780.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
fgf_pathway. FGF signaling pathway.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.
REACT_133391. Extracellular matrix organization.

Gene expression databases

Bgee

P14780.

CleanEx

HS_MMP9.

Genevestigator

P14780.

GermOnline

ENSG00000100985. Homo sapiens.

Family and domain databases

Gene3D

2.10.10.10. 3 hits.
2.110.10.10. 1 hit.
3.40.390.10. 2 hits.

InterPro

IPR000562. FN_type2_col-bd.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR013806. Kringle-like.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
IPR006970. PT.
[Graphical view]

Pfam

PF00040. fn2. 3 hits.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
PF04886. PT. 1 hit.
[Graphical view]

PRINTS

PR00138. MATRIXIN.

SMART

SM00059. FN2. 3 hits.
SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]

SUPFAM

SSF50923. Hemopexin. 1 hit.
SSF57440. Kringle-like. 3 hits.
SSF47090. PGBD_like. 1 hit.

PROSITE

PS00546. CYSTEINE_SWITCH. 1 hit.
PS00023. FN2_1. 3 hits.
PS51092. FN2_2. 3 hits.
PS00024. HEMOPEXIN. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL321.

DrugBank

DB01296. Glucosamine.
DB00786. Marimastat.
DB01017. Minocycline.
DB00641. Simvastatin.

EvolutionaryTrace

P14780.

GenomeRNAi

4318.

NextBio

16989.

SOURCE

Search...

Entry information

Entry name

MMP9_HUMAN

Accession

Primary (citable) accession number: P14780
Secondary accession number(s): B2R7V9 , Q3LR70, Q8N725, Q9H4Z1, Q9UCJ9, Q9UCL1, Q9UDK2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 174 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.