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 Genevisible; P14780; HS.
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.
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
//
