ID MMP9_HUMAN Reviewed; 707 AA. AC P14780; B2R7V9; Q3LR70; Q8N725; Q9H4Z1; Q9UCJ9; Q9UCL1; Q9UDK2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 3. DT 27-MAR-2024, entry version 265. DE RecName: Full=Matrix metalloproteinase-9; DE Short=MMP-9; DE EC=3.4.24.35 {ECO:0000269|PubMed:1480034}; DE AltName: Full=92 kDa gelatinase; DE AltName: Full=92 kDa type IV collagenase {ECO:0000303|PubMed:2551898}; DE AltName: Full=Gelatinase B; DE Short=GELB; DE Contains: DE RecName: Full=67 kDa matrix metalloproteinase-9 {ECO:0000303|PubMed:1371271}; DE Contains: DE RecName: Full=82 kDa matrix metalloproteinase-9 {ECO:0000303|PubMed:1371271}; DE Flags: Precursor; GN Name=MMP9; Synonyms=CLG4B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROTEIN SEQUENCE OF 20-37, RP SUBCELLULAR LOCATION, AND VARIANTS ARG-279 AND PRO-574. RX PubMed=2551898; DOI=10.1016/s0021-9258(18)71480-4; RA Wilhelm S.M., Collier I.E., Marmer B.L., Eisen A.Z., Grant G.A., RA Goldberg G.I.; RT "SV40-transformed human lung fibroblasts secrete a 92-kDa type IV RT collagenase which is identical to that secreted by normal human RT macrophages."; RL J. Biol. Chem. 264:17213-17221(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1653238; DOI=10.1016/s0021-9258(18)55326-6; RA Huhtala P., Tuuttila A., Chow L.T., Lohi J., Keski-Oja J., Tryggvason K.; RT "Complete structure of the human gene for 92-kDa type IV collagenase. RT Divergent regulation of expression for the 92- and 72-kilodalton enzyme RT genes in HT-1080 cells."; RL J. Biol. Chem. 266:16485-16490(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-574. RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-20; LYS-127; ARG-279; RP PRO-574 AND GLN-668. RG SeattleSNPs variation discovery resource; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-20; HIS-239; VAL-571; RP PRO-574 AND GLN-668. RG NIEHS SNPs program; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-279 AND PRO-574. RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11. RX PubMed=8426746; RA Sato H., Seiki M.; RT "Regulatory mechanism of 92 kDa type IV collagenase gene expression which RT is associated with invasiveness of tumor cells."; RL Oncogene 8:395-405(1993). RN [9] RP PROTEIN SEQUENCE OF 20-39, AND GLYCOSYLATION. RC TISSUE=Neutrophil; RX PubMed=1464361; DOI=10.1111/j.1600-0609.1992.tb00045.x; RA Kjeldsen L., Bjerrum O.W., Hovgaard D., Johnsen A.H., Sehested M., RA Borregaard N.; RT "Human neutrophil gelatinase: a marker for circulating blood neutrophils. RT Purification and quantitation by enzyme linked immunosorbent assay."; RL Eur. J. Haematol. 49:180-191(1992). RN [10] RP PROTEIN SEQUENCE OF 20-37. RX PubMed=1653055; DOI=10.1016/1043-4666(91)90021-5; RA van Ranst M., Norga K., Masure S., Proost P., Vandekerckhove F., Auwerx J., RA van Damme J., Opdenakker G.; RT "The cytokine-protease connection: identification of a 96-kD THP-1 RT gelatinase and regulation by interleukin-1 and cytokine inducers."; RL Cytokine 3:231-239(1991). RN [11] RP PROTEIN SEQUENCE OF 20-34; 60-71 AND 107-118, INDUCTION, AND PROTEOLYTIC RP PROCESSING BY MMP3. RX PubMed=1371271; DOI=10.1016/s0021-9258(19)50563-4; RA Ogata Y., Enghild J.J., Nagase H.; RT "Matrix metalloproteinase 3 (stromelysin) activates the precursor for the RT human matrix metalloproteinase 9."; RL J. Biol. Chem. 267:3581-3584(1992). RN [12] RP PROTEIN SEQUENCE OF 20-32 AND 94-111, PROTEOLYTIC PROCESSING, AND RP INDUCTION. RC TISSUE=Fibrosarcoma; RX PubMed=1400481; DOI=10.1016/s0021-9258(19)36670-0; RA Okada Y., Gonoji Y., Naka K., Tomita K., Nakanishi I., Iwata K., RA Yamashita K., Hayakawa T.; RT "Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT RT 1080 human fibrosarcoma cells. Purification and activation of the precursor RT and enzymic properties."; RL J. Biol. Chem. 267:21712-21719(1992). RN [13] RP PROTEIN SEQUENCE OF 20-27; 60-67; 94-101 AND 107-113. RX PubMed=7669817; DOI=10.1016/0167-4838(95)00086-a; RA Sang Q.X., Birkedal-Hansen H., Van Wart H.E.; RT "Proteolytic and non-proteolytic activation of human neutrophil RT progelatinase B."; RL Biochim. Biophys. Acta 1251:99-108(1995). RN [14] RP PROTEIN SEQUENCE OF 28-60. RC TISSUE=Neutrophil; RX PubMed=1645657; DOI=10.1111/j.1432-1033.1991.tb16027.x; RA Masure S., Proost P., van Damme J., Opdenakker G.; RT "Purification and identification of 91-kDa neutrophil gelatinase. Release RT by the activating peptide interleukin-8."; RL Eur. J. Biochem. 198:391-398(1991). RN [15] RP PROTEIN SEQUENCE OF 28-37. RX PubMed=1932376; RA Opdenakker G., Masure S., Grillet B., Van Damme J.; RT "Cytokine-mediated regulation of human leukocyte gelatinases and role in RT arthritis."; RL Lymphokine Cytokine Res. 10:317-324(1991). RN [16] RP PROTEIN SEQUENCE OF 93-115, FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Blood; RX PubMed=1480034; RA Tschesche H., Knaeuper V., Kraemer S., Michaelis J., Oberhoff R., RA Reinke H.; RT "Latent collagenase and gelatinase from human neutrophils and their RT activation."; RL Matrix Suppl. 1:245-255(1992). RN [17] RP PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LCN2, AND SUBUNIT. RX PubMed=1281792; DOI=10.1016/0014-5793(92)81511-j; RA Triebel S., Blaeser J., Reinke H., Tschesche H.; RT "A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 RT kDa form of human gelatinase."; RL FEBS Lett. 314:386-388(1992). RN [18] RP INTERACTION WITH LCN2, TISSUE SPECIFICITY, AND SUBUNIT. RX PubMed=7683678; DOI=10.1016/s0021-9258(18)82217-7; RA Kjeldsen L., Johnsen A.H., Sengelov H., Borregaard N.; RT "Isolation and primary structure of NGAL, a novel protein associated with RT human neutrophil gelatinase."; RL J. Biol. Chem. 268:10425-10432(1993). RN [19] RP CHARACTERIZATION. RA Kang K., Lee D.-H.; RT "Purification and characterization of human 92-kDa type IV collagenase RT (gelatinase B)."; RL Exp. Mol. Med. 28:161-165(1996). RN [20] RP SUBUNIT. RX PubMed=10644727; DOI=10.1074/jbc.275.4.2661; RA Olson M.W., Bernardo M.M., Pietila M., Gervasi D.C., Toth M., Kotra L.P., RA Massova I., Mobashery S., Fridman R.; RT "Characterization of the monomeric and dimeric forms of latent and active RT matrix metalloproteinase-9. Differential rates for activation by RT stromelysin 1."; RL J. Biol. Chem. 275:2661-2668(2000). RN [21] RP ACTIVITY REGULATION. RX PubMed=11179305; DOI=10.1128/iai.69.3.1402-1408.2001; RA Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F., RA Oppenheim F.G.; RT "Salivary histatin 5 is an inhibitor of both host and bacterial enzymes RT implicated in periodontal disease."; RL Infect. Immun. 69:1402-1408(2001). RN [22] RP FUNCTION, AND PROTEOLYTIC PROCESSING OF KISS1. RX PubMed=12879005; DOI=10.1038/sj.onc.1206542; RA Takino T., Koshikawa N., Miyamori H., Tanaka M., Sasaki T., Okada Y., RA Seiki M., Sato H.; RT "Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by RT matrix metalloproteinases."; RL Oncogene 22:4617-4626(2003). RN [23] RP INTERACTION WITH ECM1, AND ACTIVITY REGULATION. RX PubMed=16512877; DOI=10.1111/j.0906-6705.2006.00409.x; RA Fujimoto N., Terlizzi J., Aho S., Brittingham R., Fertala A., Oyama N., RA McGrath J.A., Uitto J.; RT "Extracellular matrix protein 1 inhibits the activity of matrix RT metalloproteinase 9 through high-affinity protein/protein interactions."; RL Exp. Dermatol. 15:300-307(2006). RN [24] RP INVOLVEMENT IN SUSCEPTIBILITY TO IDD. RX PubMed=18455130; DOI=10.1016/j.ajhg.2008.03.013; RA Hirose Y., Chiba K., Karasugi T., Nakajima M., Kawaguchi Y., Mikami Y., RA Furuichi T., Mio F., Miyake A., Miyamoto T., Ozaki K., Takahashi A., RA Mizuta H., Kubo T., Kimura T., Tanaka T., Toyama Y., Ikegawa S.; RT "A functional polymorphism in THBS2 that affects alternative splicing and RT MMP binding is associated with lumbar-disc herniation."; RL Am. J. Hum. Genet. 82:1122-1129(2008). RN [25] RP INVOLVEMENT IN MANDP2. RX PubMed=19615667; DOI=10.1016/j.ajhg.2009.06.014; RA Lausch E., Keppler R., Hilbert K., Cormier-Daire V., Nikkel S., RA Nishimura G., Unger S., Spranger J., Superti-Furga A., Zabel B.; RT "Mutations in MMP9 and MMP13 determine the mode of inheritance and the RT clinical spectrum of metaphyseal anadysplasia."; RL Am. J. Hum. Genet. 85:168-178(2009). RN [26] RP INDUCTION. RX PubMed=19893577; DOI=10.1038/embor.2009.233; RA Kawasaki Y., Tsuji S., Muroya K., Furukawa S., Shibata Y., Okuno M., RA Ohwada S., Akiyama T.; RT "The adenomatous polyposis coli-associated exchange factors Asef and Asef2 RT are required for adenoma formation in Apc(Min/+)mice."; RL EMBO Rep. 10:1355-1362(2009). RN [27] RP INDUCTION BY M.BOVIS MPB83. RC TISSUE=Monocytic leukemia; RX PubMed=20800577; DOI=10.1016/j.bbrc.2010.08.085; RA Chambers M.A., Whelan A.O., Spallek R., Singh M., Coddeville B., RA Guerardel Y., Elass E.; RT "Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and RT stimulates production of matrix metalloproteinase 9."; RL Biochem. Biophys. Res. Commun. 400:403-408(2010). RN [28] RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN SSL5 (MICROBIAL INFECTION). RX PubMed=20479083; DOI=10.1128/iai.00178-10; RA Itoh S., Hamada E., Kamoshida G., Takeshita K., Oku T., Tsuji T.; RT "Staphylococcal superantigen-like protein 5 inhibits matrix RT metalloproteinase 9 from human neutrophils."; RL Infect. Immun. 78:3298-3305(2010). RN [29] RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN SSL5 (MICROBIAL INFECTION). RX PubMed=29328525; DOI=10.1111/1348-0421.12573; RA Kurisaka C., Oku T., Itoh S., Tsuji T.; RT "Role of sialic acid-containing glycans of matrix metalloproteinase-9 (MMP- RT 9) in the interaction between MMP-9 and staphylococcal superantigen-like RT protein 5."; RL Microbiol. Immunol. 62:168-175(2018). RN [30] RP FUNCTION. RX PubMed=32883094; DOI=10.1161/circulationaha.120.046907; RA Jeon S., Kim T.K., Jeong S.J., Jung I.H., Kim N., Lee M.N., Sonn S.K., RA Seo S., Jin J., Kweon H.Y., Kim S., Shim D., Park Y.M., Lee S.H., Kim K.W., RA Cybulsky M.I., Shim H., Roh T.Y., Park W.Y., Lee H.O., Choi J.H., RA Park S.H., Oh G.T.; RT "Anti-inflammatory actions of soluble ninjurin-1 ameliorate RT atherosclerosis."; RL Circulation 142:1736-1751(2020). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-444 IN COMPLEX WITH ZINC AND RP MAGNESIUM IONS, COFACTOR, AND DOMAIN. RX PubMed=12077439; DOI=10.1107/s0907444902007849; RA Elkins P.A., Ho Y.S., Smith W.W., Janson C.A., D'Alessio K.J., RA McQueney M.S., Cummings M.D., Romanic A.M.; RT "Structure of the C-terminally truncated human ProMMP9, a gelatin-binding RT matrix metalloproteinase."; RL Acta Crystallogr. D 58:1182-1192(2002). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 107-215 IN COMPLEX WITH INHIBITOR; RP ZINC AND CALCIUM IONS, COFACTOR, ACTIVE SITE, AND MUTAGENESIS OF GLU-402. RX PubMed=12051944; DOI=10.1016/s0022-2836(02)00262-0; RA Rowsell S., Hawtin P., Minshull C.A., Jepson H., Brockbank S.M.V., RA Barratt D.G., Slater A.M., McPheat W.L., Waterson D., Henney A.M., RA Pauptit R.A.; RT "Crystal structure of human MMP9 in complex with a reverse hydroxamate RT inhibitor."; RL J. Mol. Biol. 319:173-181(2002). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 513-707, SUBUNIT, AND DISULFIDE RP BOND. RX PubMed=12126625; DOI=10.1016/s0022-2836(02)00558-2; RA Cha H., Kopetzki E., Huber R., Lanzendoerfer M., Brandstetter H.; RT "Structural basis of the adaptive molecular recognition by MMP9."; RL J. Mol. Biol. 320:1065-1079(2002). RN [34] RP VARIANTS VAL-20; LYS-82 AND ARG-279. RX PubMed=10598806; DOI=10.1007/s004390051124; RA Zhang B., Henney A., Eriksson P., Hamsten A., Watkins H., Ye S.; RT "Genetic variation at the matrix metalloproteinase-9 locus on chromosome RT 20q12.2-13.1."; RL Hum. Genet. 105:418-423(1999). CC -!- FUNCTION: Matrix metalloproteinase that plays an essential role in CC local proteolysis of the extracellular matrix and in leukocyte CC migration (PubMed:2551898, PubMed:1480034, PubMed:12879005). Could play CC a role in bone osteoclastic resorption (By similarity). Cleaves KiSS1 CC at a Gly-|-Leu bond (PubMed:12879005). Cleaves NINJ1 to generate the CC Secreted ninjurin-1 form (PubMed:32883094). Cleaves type IV and type V CC collagen into large C-terminal three quarter fragments and shorter N- CC terminal one quarter fragments (PubMed:1480034). Degrades fibronectin CC but not laminin or Pz-peptide. {ECO:0000250|UniProtKB:P41245, CC ECO:0000269|PubMed:12879005, ECO:0000269|PubMed:1480034, CC ECO:0000269|PubMed:2551898, ECO:0000269|PubMed:32883094}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of gelatin types I and V and collagen types IV and CC V.; EC=3.4.24.35; Evidence={ECO:0000269|PubMed:1480034}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:12051944}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:12051944}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:12051944}; CC Note=Binds 3 Ca(2+) ions per subunit.; CC -!- ACTIVITY REGULATION: Inhibited by histatin-3 1/24 (histatin-5). CC Inhibited by ECM1. {ECO:0000269|PubMed:11179305, CC ECO:0000269|PubMed:16512877}. CC -!- SUBUNIT: Exists as monomer or homodimer; disulfide-linked CC (PubMed:1281792, PubMed:7683678). Exists also as heterodimer with LCN2 CC (PubMed:1281792, PubMed:7683678). Macrophages and transformed cell CC lines produce only the monomeric form. Interacts with ECM1 CC (PubMed:16512877). {ECO:0000269|PubMed:10644727, CC ECO:0000269|PubMed:12051944, ECO:0000269|PubMed:12077439, CC ECO:0000269|PubMed:12126625, ECO:0000269|PubMed:1281792, CC ECO:0000269|PubMed:16512877, ECO:0000269|PubMed:7683678}. CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus CC protein SSL5; this interaction inhibits MMP9 activity. CC {ECO:0000269|PubMed:20479083, ECO:0000269|PubMed:29328525}. CC -!- INTERACTION: CC P14780; Q16819: MEP1A; NbExp=2; IntAct=EBI-1382326, EBI-8153734; CC P14780; Q16820: MEP1B; NbExp=2; IntAct=EBI-1382326, EBI-968418; CC P14780; P14780: MMP9; NbExp=4; IntAct=EBI-1382326, EBI-1382326; CC P14780; Q8IX30: SCUBE3; NbExp=2; IntAct=EBI-1382326, EBI-4479975; CC P14780; P13611: VCAN; NbExp=3; IntAct=EBI-1382326, EBI-8515977; CC P14780; Q9ZFS6: set3; Xeno; NbExp=2; IntAct=EBI-1382326, EBI-26361542; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000269|PubMed:2551898}. CC -!- TISSUE SPECIFICITY: Detected in neutrophils (at protein level) CC (PubMed:7683678). Produced by normal alveolar macrophages and CC granulocytes. {ECO:0000269|PubMed:7683678}. CC -!- INDUCTION: Activated by 4-aminophenylmercuric acetate and phorbol CC ester. Up-regulated by ARHGEF4, SPATA13 and APC via the JNK signaling CC pathway in colorectal tumor cells. {ECO:0000269|PubMed:1371271, CC ECO:0000269|PubMed:1400481, ECO:0000269|PubMed:19893577}. CC -!- INDUCTION: (Microbial infection) Expression induced by M.bovis MPB83 CC (at protein level) (PubMed:20800577). {ECO:0000269|PubMed:20800577}. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif CC binds the catalytic zinc ion, thus inhibiting the enzyme. The CC dissociation of the cysteine from the zinc ion upon the activation- CC peptide release activates the enzyme. {ECO:0000269|PubMed:12077439}. CC -!- PTM: Processing of the precursor yields different active forms of 64, CC 67 and 82 kDa. Sequentially processing by MMP3 yields the 82 kDa matrix CC metalloproteinase-9. {ECO:0000269|PubMed:1371271, CC ECO:0000269|PubMed:1400481}. CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:1464361}. CC -!- DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common CC musculo-skeletal disorder caused by degeneration of intervertebral CC disks of the lumbar spine. It results in low-back pain and unilateral CC leg pain. {ECO:0000269|PubMed:18455130}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Metaphyseal anadysplasia 2 (MANDP2) [MIM:613073]: A bone CC development disorder characterized by skeletal anomalies that resolve CC spontaneously with age. Clinical characteristics are evident from the CC first months of life and include slight shortness of stature and a mild CC varus deformity of the legs. Patients attain a normal stature in CC adolescence and show improvement or complete resolution of varus CC deformity of the legs and rhizomelic micromelia. CC {ECO:0000269|PubMed:19615667}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: In the arthritis patient this enzyme might contribute to CC the pathogenesis of joint destruction and might constitute a useful CC marker of disease status. CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41408/MMP9"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mmp9/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/mmp9/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J05070; AAA51539.1; -; mRNA. DR EMBL; M68343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68344; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68345; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68346; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68347; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68348; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68349; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68350; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68351; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68353; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68354; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M68355; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK313137; BAG35956.1; -; mRNA. DR EMBL; AF538844; AAM97934.1; -; Genomic_DNA. DR EMBL; DQ194553; ABA03169.1; -; Genomic_DNA. DR EMBL; AL162458; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006093; AAH06093.1; -; mRNA. DR EMBL; D10051; BAA20967.1; -; Genomic_DNA. DR CCDS; CCDS13390.1; -. DR PIR; A34458; A34458. DR RefSeq; NP_004985.2; NM_004994.2. DR PDB; 1GKC; X-ray; 2.30 A; A/B=107-443. DR PDB; 1GKD; X-ray; 2.10 A; A/B=107-443. DR PDB; 1ITV; X-ray; 1.95 A; A/B=513-707. DR PDB; 1L6J; X-ray; 2.50 A; A=20-444. DR PDB; 2OVX; X-ray; 2.00 A; A/B=110-443. DR PDB; 2OVZ; X-ray; 2.00 A; A/B=110-443. DR PDB; 2OW0; X-ray; 2.00 A; A/B=110-443. DR PDB; 2OW1; X-ray; 2.20 A; A/B=110-443. DR PDB; 2OW2; X-ray; 2.90 A; A/B=110-443. DR PDB; 4H1Q; X-ray; 1.59 A; A/B=110-214, A/B=391-444. DR PDB; 4H2E; X-ray; 2.90 A; A/B=107-216, A/B=392-444. DR PDB; 4H3X; X-ray; 1.76 A; A/B=107-216, A/B=392-444. DR PDB; 4H82; X-ray; 1.90 A; A/B/C/D=110-444. DR PDB; 4HMA; X-ray; 1.94 A; A/B=110-214, A/B=391-444. DR PDB; 4JIJ; X-ray; 1.70 A; A/B=107-444. DR PDB; 4JQG; X-ray; 1.85 A; A/B=107-444. DR PDB; 4WZV; X-ray; 1.65 A; A/B=110-444. DR PDB; 4XCT; X-ray; 1.30 A; A=113-444. DR PDB; 5CUH; X-ray; 1.83 A; A/B=107-444. DR PDB; 5I12; X-ray; 1.59 A; A=113-444. DR PDB; 5TH6; X-ray; 1.70 A; A/B/C/D=40-443. DR PDB; 5TH9; X-ray; 3.00 A; A/B/C=40-443. DR PDB; 5UE3; X-ray; 1.60 A; A/B=35-445. DR PDB; 5UE4; X-ray; 1.80 A; A/B=35-445. DR PDB; 6ESM; X-ray; 1.10 A; A=110-227. DR PDB; 8K5V; X-ray; 1.70 A; A/B=28-444. DR PDB; 8K5W; X-ray; 2.00 A; A/B=28-444. DR PDB; 8K5X; X-ray; 1.90 A; A/B=28-444. DR PDB; 8K5Y; X-ray; 1.52 A; A/B=28-444. DR PDBsum; 1GKC; -. DR PDBsum; 1GKD; -. DR PDBsum; 1ITV; -. DR PDBsum; 1L6J; -. DR PDBsum; 2OVX; -. DR PDBsum; 2OVZ; -. DR PDBsum; 2OW0; -. DR PDBsum; 2OW1; -. DR PDBsum; 2OW2; -. DR PDBsum; 4H1Q; -. DR PDBsum; 4H2E; -. DR PDBsum; 4H3X; -. DR PDBsum; 4H82; -. DR PDBsum; 4HMA; -. DR PDBsum; 4JIJ; -. DR PDBsum; 4JQG; -. DR PDBsum; 4WZV; -. DR PDBsum; 4XCT; -. DR PDBsum; 5CUH; -. DR PDBsum; 5I12; -. DR PDBsum; 5TH6; -. DR PDBsum; 5TH9; -. DR PDBsum; 5UE3; -. DR PDBsum; 5UE4; -. DR PDBsum; 6ESM; -. DR PDBsum; 8K5V; -. DR PDBsum; 8K5W; -. DR PDBsum; 8K5X; -. DR PDBsum; 8K5Y; -. DR AlphaFoldDB; P14780; -. DR SMR; P14780; -. DR BioGRID; 110461; 47. DR CORUM; P14780; -. DR DIP; DIP-29518N; -. DR IntAct; P14780; 24. DR MINT; P14780; -. DR STRING; 9606.ENSP00000361405; -. DR BindingDB; P14780; -. DR ChEMBL; CHEMBL321; -. DR DrugBank; DB07246; (2R)-2-AMINO-3,3,3-TRIFLUORO-N-HYDROXY-2-{[(4-PHENOXYPHENYL)SULFONYL]METHYL}PROPANAMIDE. DR DrugBank; DB07285; (3R)-4,4-DIFLUORO-3-[(4-METHOXYPHENYL)SULFONYL]BUTANOIC ACID. DR DrugBank; DB01949; 2-Amino-N,3,3-Trimethylbutanamide. DR DrugBank; DB03683; 2-{[Formyl(Hydroxy)Amino]Methyl}-4-Methylpentanoic Acid. DR DrugBank; DB07117; 5-(4-PHENOXYPHENYL)-5-(4-PYRIMIDIN-2-YLPIPERAZIN-1-YL)PYRIMIDINE-2,4,6(2H,3H)-TRIONE. DR DrugBank; DB05387; AE-941. DR DrugBank; DB01197; Captopril. DR DrugBank; DB06423; Endostatin. DR DrugBank; DB00143; Glutathione. DR DrugBank; DB00786; Marimastat. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB12843; Oleandrin. DR DrugBank; DB05495; PG-530742. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR DrugCentral; P14780; -. DR GuidetoPHARMACOLOGY; 1633; -. DR MEROPS; M10.004; -. DR GlyConnect; 6; 1 N-Linked glycan (1 site), 19 O-Linked glycans. DR GlyCosmos; P14780; 3 sites, 30 glycans. DR GlyGen; P14780; 4 sites, 1 N-linked glycan (1 site), 29 O-linked glycans (1 site). DR iPTMnet; P14780; -. DR PhosphoSitePlus; P14780; -. DR BioMuta; MMP9; -. DR DMDM; 269849668; -. DR EPD; P14780; -. DR jPOST; P14780; -. DR MassIVE; P14780; -. DR PaxDb; 9606-ENSP00000361405; -. DR PeptideAtlas; P14780; -. DR PRIDE; P14780; -. DR ProteomicsDB; 53082; -. DR Pumba; P14780; -. DR ABCD; P14780; 16 sequenced antibodies. DR Antibodypedia; 774; 2306 antibodies from 53 providers. DR DNASU; 4318; -. DR Ensembl; ENST00000372330.3; ENSP00000361405.3; ENSG00000100985.7. DR GeneID; 4318; -. DR KEGG; hsa:4318; -. DR MANE-Select; ENST00000372330.3; ENSP00000361405.3; NM_004994.3; NP_004985.2. DR UCSC; uc002xqz.3; human. DR AGR; HGNC:7176; -. DR CTD; 4318; -. DR DisGeNET; 4318; -. DR GeneCards; MMP9; -. DR HGNC; HGNC:7176; MMP9. DR HPA; ENSG00000100985; Group enriched (bone marrow, lymphoid tissue). DR MalaCards; MMP9; -. DR MIM; 120361; gene. DR MIM; 603932; phenotype. DR MIM; 613073; phenotype. DR neXtProt; NX_P14780; -. DR OpenTargets; ENSG00000100985; -. DR Orphanet; 1040; Metaphyseal anadysplasia. DR PharmGKB; PA30889; -. DR VEuPathDB; HostDB:ENSG00000100985; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000157415; -. DR HOGENOM; CLU_015489_6_2_1; -. DR InParanoid; P14780; -. DR OMA; REKAYFC; -. DR OrthoDB; 5340816at2759; -. DR PhylomeDB; P14780; -. DR TreeFam; TF315428; -. DR BRENDA; 3.4.24.35; 2681. DR PathwayCommons; P14780; -. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling. DR SignaLink; P14780; -. DR SIGNOR; P14780; -. DR BioGRID-ORCS; 4318; 9 hits in 1155 CRISPR screens. DR EvolutionaryTrace; P14780; -. DR GeneWiki; MMP9; -. DR GenomeRNAi; 4318; -. DR Pharos; P14780; Tchem. DR PRO; PR:P14780; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P14780; Protein. DR Bgee; ENSG00000100985; Expressed in periodontal ligament and 143 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome. DR GO; GO:0005518; F:collagen binding; TAS:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; EXP:Reactome. DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl. DR GO; GO:0016477; P:cell migration; IGI:ARUK-UCL. DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:CAFA. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; TAS:ARUK-UCL. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:CAFA. DR GO; GO:0071492; P:cellular response to UV-A; IDA:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central. DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl. DR GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB. DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:CACAO. DR GO; GO:2001258; P:negative regulation of cation channel activity; IDA:UniProtKB. DR GO; GO:2001268; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:CACAO. DR GO; GO:2000697; P:negative regulation of epithelial cell differentiation involved in kidney development; ISS:ARUK-UCL. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:CACAO. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:CACAO. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:CACAO. DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IMP:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:CACAO. DR GO; GO:1900122; P:positive regulation of receptor binding; IDA:UniProtKB. DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:CACAO. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0150077; P:regulation of neuroinflammatory response; TAS:ARUK-UCL. DR GO; GO:1904645; P:response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl. DR CDD; cd00062; FN2; 3. DR CDD; cd00094; HX; 1. DR CDD; cd04278; ZnMc_MMP; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 2. DR Gene3D; 2.10.10.10; Fibronectin, type II, collagen-binding; 2. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 1. DR InterPro; IPR000562; FN_type2_dom. DR InterPro; IPR036943; FN_type2_sf. DR InterPro; IPR000585; Hemopexin-like_dom. DR InterPro; IPR036375; Hemopexin-like_dom_sf. DR InterPro; IPR018487; Hemopexin-like_repeat. DR InterPro; IPR018486; Hemopexin_CS. DR InterPro; IPR013806; Kringle-like. DR InterPro; IPR033739; M10A_MMP. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR001818; Pept_M10_metallopeptidase. DR InterPro; IPR021190; Pept_M10A. DR InterPro; IPR021158; Pept_M10A_Zn_BS. DR InterPro; IPR006026; Peptidase_Metallo. DR InterPro; IPR036365; PGBD-like_sf. DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1. DR PANTHER; PTHR10201:SF30; MATRIX METALLOPROTEINASE-9; 1. DR Pfam; PF00040; fn2; 3. DR Pfam; PF00045; Hemopexin; 4. DR Pfam; PF00413; Peptidase_M10; 2. DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1. DR PRINTS; PR00013; FNTYPEII. DR PRINTS; PR00138; MATRIXIN. DR SMART; SM00059; FN2; 3. DR SMART; SM00120; HX; 4. DR SMART; SM00235; ZnMc; 1. DR SUPFAM; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF57440; Kringle-like; 3. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF47090; PGBD-like; 1. DR PROSITE; PS00546; CYSTEINE_SWITCH; 1. DR PROSITE; PS00023; FN2_1; 3. DR PROSITE; PS51092; FN2_2; 3. DR PROSITE; PS00024; HEMOPEXIN; 1. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P14780; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Collagen degradation; Direct protein sequencing; KW Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat; KW Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:1371271, FT ECO:0000269|PubMed:1400481, ECO:0000269|PubMed:1464361, FT ECO:0000269|PubMed:1653055, ECO:0000269|PubMed:2551898, FT ECO:0000269|PubMed:7669817" FT PROPEP 20..93 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:1400481" FT /id="PRO_0000028754" FT CHAIN 94..? FT /note="67 kDa matrix metalloproteinase-9" FT /evidence="ECO:0000305|PubMed:1371271" FT /id="PRO_0000028755" FT CHAIN 107..707 FT /note="82 kDa matrix metalloproteinase-9" FT /evidence="ECO:0000305|PubMed:1371271" FT /id="PRO_0000028756" FT PROPEP ?..707 FT /note="Removed in 64 kDa matrix metalloproteinase-9 and 67 FT kDa matrix metalloproteinase-9" FT /id="PRO_0000028757" FT DOMAIN 225..273 FT /note="Fibronectin type-II 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DOMAIN 283..331 FT /note="Fibronectin type-II 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DOMAIN 342..390 FT /note="Fibronectin type-II 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT REPEAT 518..563 FT /note="Hemopexin 1" FT REPEAT 564..608 FT /note="Hemopexin 2" FT REPEAT 610..657 FT /note="Hemopexin 3" FT REPEAT 658..704 FT /note="Hemopexin 4" FT REGION 431..508 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 97..104 FT /note="Cysteine switch" FT /evidence="ECO:0000303|PubMed:12077439" FT COMPBIAS 431..447 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 448..496 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 402 FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 99 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 131 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 165 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 175 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 177 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 182 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 183 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 185 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 187 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 190 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 197 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 203 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 206 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12051944" FT BINDING 401 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 405 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT BINDING 411 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12051944, FT ECO:0000269|PubMed:12077439" FT SITE 59..60 FT /note="Cleavage; by MMP3" FT /evidence="ECO:0000269|PubMed:1371271" FT SITE 106..107 FT /note="Cleavage; by MMP3" FT /evidence="ECO:0000269|PubMed:1371271" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 127 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 230..256 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 244..271 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 288..314 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 302..329 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 347..373 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 361..388 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DISULFID 516..704 FT /evidence="ECO:0000269|PubMed:12126625" FT VARIANT 20 FT /note="A -> V (in dbSNP:rs1805088)" FT /evidence="ECO:0000269|PubMed:10598806, ECO:0000269|Ref.4, FT ECO:0000269|Ref.5" FT /id="VAR_013780" FT VARIANT 38 FT /note="N -> S (in dbSNP:rs41427445)" FT /id="VAR_037004" FT VARIANT 82 FT /note="E -> K (in dbSNP:rs1805089)" FT /evidence="ECO:0000269|PubMed:10598806" FT /id="VAR_013781" FT VARIANT 127 FT /note="N -> K (in dbSNP:rs3918252)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020054" FT VARIANT 239 FT /note="R -> H (in dbSNP:rs28763886)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025165" FT VARIANT 279 FT /note="Q -> R (risk factor for IDD; dbSNP:rs17576)" FT /evidence="ECO:0000269|PubMed:10598806, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2551898, FT ECO:0000269|Ref.4" FT /id="VAR_013782" FT VARIANT 571 FT /note="F -> V (in dbSNP:rs35691798)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025166" FT VARIANT 574 FT /note="R -> P (in dbSNP:rs2250889)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2551898, FT ECO:0000269|Ref.4, ECO:0000269|Ref.5" FT /id="VAR_024595" FT VARIANT 668 FT /note="R -> Q (in dbSNP:rs17577)" FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5" FT /id="VAR_014742" FT MUTAGEN 402 FT /note="E->Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:12051944" FT CONFLICT 110 FT /note="F -> L (in Ref. 3; BAG35956)" FT /evidence="ECO:0000305" FT HELIX 42..51 FT /evidence="ECO:0007829|PDB:5UE3" FT HELIX 54..60 FT /evidence="ECO:0007829|PDB:5UE3" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:5UE3" FT HELIX 68..78 FT /evidence="ECO:0007829|PDB:5UE3" FT HELIX 88..94 FT /evidence="ECO:0007829|PDB:5UE3" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:5UE3" FT STRAND 111..115 FT /evidence="ECO:0007829|PDB:5UE3" FT STRAND 117..125 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:5UE3" FT HELIX 134..149 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 151..153 FT /evidence="ECO:0007829|PDB:4WZV" FT STRAND 155..158 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:4JIJ" FT STRAND 165..171 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 176..178 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 183..186 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:6ESM" FT TURN 197..200 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 202..205 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 221..225 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 232..238 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 240..243 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 255..261 FT /evidence="ECO:0007829|PDB:1L6J" FT HELIX 262..265 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 268..270 FT /evidence="ECO:0007829|PDB:1L6J" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 279..283 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 290..294 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 297..301 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 313..319 FT /evidence="ECO:0007829|PDB:1L6J" FT HELIX 320..323 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:1L6J" FT HELIX 333..335 FT /evidence="ECO:0007829|PDB:1L6J" FT TURN 340..344 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 349..353 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 372..378 FT /evidence="ECO:0007829|PDB:1L6J" FT HELIX 379..382 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 385..387 FT /evidence="ECO:0007829|PDB:1L6J" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:6ESM" FT HELIX 395..406 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 420..422 FT /evidence="ECO:0007829|PDB:6ESM" FT STRAND 427..429 FT /evidence="ECO:0007829|PDB:4H2E" FT HELIX 433..443 FT /evidence="ECO:0007829|PDB:6ESM" FT HELIX 515..517 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 522..527 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 530..535 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 538..542 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 545..547 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 551..555 FT /evidence="ECO:0007829|PDB:1ITV" FT HELIX 556..559 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 568..572 FT /evidence="ECO:0007829|PDB:1ITV" FT TURN 574..576 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 579..583 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 586..591 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 594..600 FT /evidence="ECO:0007829|PDB:1ITV" FT HELIX 601..604 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 615..618 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 623..628 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 631..636 FT /evidence="ECO:0007829|PDB:1ITV" FT TURN 637..640 FT /evidence="ECO:0007829|PDB:1ITV" FT HELIX 644..646 FT /evidence="ECO:0007829|PDB:1ITV" FT HELIX 650..653 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 662..667 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 670..675 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 678..683 FT /evidence="ECO:0007829|PDB:1ITV" FT STRAND 690..696 FT /evidence="ECO:0007829|PDB:1ITV" FT TURN 697..700 FT /evidence="ECO:0007829|PDB:1ITV" SQ SEQUENCE 707 AA; 78458 MW; 2165AC8CA1466209 CRC64; MSLWQPLVLV LLVLGCCFAA PRQRQSTLVL FPGDLRTNLT DRQLAEEYLY RYGYTRVAEM RGESKSLGPA LLLLQKQLSL PETGELDSAT LKAMRTPRCG VPDLGRFQTF EGDLKWHHHN ITYWIQNYSE DLPRAVIDDA FARAFALWSA VTPLTFTRVY SRDADIVIQF GVAEHGDGYP FDGKDGLLAH AFPPGPGIQG DAHFDDDELW SLGKGVVVPT RFGNADGAAC HFPFIFEGRS YSACTTDGRS DGLPWCSTTA NYDTDDRFGF CPSERLYTQD GNADGKPCQF PFIFQGQSYS ACTTDGRSDG YRWCATTANY DRDKLFGFCP TRADSTVMGG NSAGELCVFP FTFLGKEYST CTSEGRGDGR LWCATTSNFD SDKKWGFCPD QGYSLFLVAA HEFGHALGLD HSSVPEALMY PMYRFTEGPP LHKDDVNGIR HLYGPRPEPE PRPPTTTTPQ PTAPPTVCPT GPPTVHPSER PTAGPTGPPS AGPTGPPTAG PSTATTVPLS PVDDACNVNI FDAIAEIGNQ LYLFKDGKYW RFSEGRGSRP QGPFLIADKW PALPRKLDSV FEERLSKKLF FFSGRQVWVY TGASVLGPRR LDKLGLGADV AQVTGALRSG RGKMLLFSGR RLWRFDVKAQ MVDPRSASEV DRMFPGVPLD THDVFQYREK AYFCQDRFYW RVSSRSELNQ VDQVGYVTYD ILQCPED //