ID MMP2_HUMAN Reviewed; 660 AA. AC P08253; B2R6U1; B4DWH3; E9PE45; Q9UCJ8; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 2. DT 27-MAR-2024, entry version 258. DE RecName: Full=72 kDa type IV collagenase {ECO:0000303|PubMed:2162831, ECO:0000303|PubMed:2834383}; DE EC=3.4.24.24 {ECO:0000305|PubMed:11179305, ECO:0000305|PubMed:11431697, ECO:0000305|PubMed:12147339, ECO:0000305|PubMed:2834383}; DE AltName: Full=72 kDa gelatinase {ECO:0000303|PubMed:1655733}; DE AltName: Full=Gelatinase A; DE AltName: Full=Matrix metalloproteinase-2; DE Short=MMP-2; DE AltName: Full=TBE-1; DE Contains: DE RecName: Full=PEX; DE Flags: Precursor; GN Name=MMP2; Synonyms=CLG4A; 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 [GENOMIC DNA]. RX PubMed=2162831; DOI=10.1016/s0021-9258(19)38559-x; RA Huhtala P., Chow L.T., Tryggvason K.; RT "Structure of the human type IV collagenase gene."; RL J. Biol. Chem. 265:11077-11082(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1851724; DOI=10.1016/0888-7543(91)90408-7; RA Collier I.E., Bruns G.A.P., Goldberg G.I., Gerhard D.S.; RT "On the structure and chromosome location of the 72- and 92-kDa human type RT IV collagenase genes."; RL Genomics 9:429-434(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Teratocarcinoma, and Testis; 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-447 AND LEU-621. RG NIEHS SNPs program; RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51. RX PubMed=2158484; DOI=10.1016/0888-7543(90)90486-e; RA Huhtala P., Eddy R.L., Fan Y.S., Byers M.G., Shows T.B., Tryggvason K.; RT "Completion of the primary structure of the human type IV collagenase RT preproenzyme and assignment of the gene (CLG4) to the q21 region of RT chromosome 16."; RL Genomics 6:554-559(1990). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-660 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, RP SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=2834383; DOI=10.1016/s0021-9258(18)68680-6; RA Collier I.E., Wilhelm S.M., Eisen A.Z., Marmer B.L., Grant G.A., RA Seltzer J.L., Kronberger A., He C., Bauer E.A., Goldberg G.I.; RT "H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) RT secrete a single metalloprotease capable of degrading basement membrane RT collagen."; RL J. Biol. Chem. 263:6579-6587(1988). RN [9] RP PROTEIN SEQUENCE OF 30-44. RC TISSUE=Melanoma; RX PubMed=1480041; RA Stetler-Stevenson W.G., Krutzsch H.C., Liotta L.A.; RT "TIMP-2: identification and characterization of a new member of the RT metalloproteinase inhibitor family."; RL Matrix Suppl. 1:299-306(1992). RN [10] RP INTERACTION WITH TIMP2. RX PubMed=1655733; DOI=10.1016/s0021-9258(18)55224-8; RA Howard E.W., Banda M.J.; RT "Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites RT on human 72-kDa gelatinase. Identification of a stabilization site."; RL J. Biol. Chem. 266:17972-17977(1991). RN [11] RP IDENTIFICATION OF RECEPTOR, AND SUBCELLULAR LOCATION. RX PubMed=8646777; DOI=10.1016/s0092-8674(00)81235-0; RA Brooks P.C., Stroemblad S., Sanders L.C., von Schalscha T.L., Aimes R.T., RA Stetler-Stevenson W.G., Quigley J.P., Cheresh D.A.; RT "Localization of matrix metalloproteinase MMP-2 to the surface of invasive RT cells by interaction with integrin alpha v beta 3."; RL Cell 85:683-693(1996). RN [12] RP PROTEOLYTIC PROCESSING. RX PubMed=9119036; DOI=10.1111/j.1432-1033.1997.t01-1-00653.x; RA Butler G.S., Will H., Atkinson S.J., Murphy G.; RT "Membrane-type-2 matrix metalloproteinase can initiate the processing of RT progelatinase A and is regulated by the tissue inhibitors of RT metalloproteinases."; RL Eur. J. Biochem. 244:653-657(1997). RN [13] RP IDENTIFICATION OF RECEPTOR, AND FUNCTION OF PEX. RX PubMed=9476898; DOI=10.1016/s0092-8674(00)80931-9; RA Brooks P.C., Silletti S., von Schalscha T.L., Friedlander M., Cheresh D.A.; RT "Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase RT fragment with integrin binding activity."; RL Cell 92:391-400(1998). RN [14] RP FUNCTION. RX PubMed=10559137; DOI=10.1161/01.res.85.10.906; RA Fernandez-Patron C., Radomski M.W., Davidge S.T.; RT "Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a RT novel vasoconstrictor."; RL Circ. Res. 85:906-911(1999). RN [15] RP FUNCTION. RX PubMed=11029402; DOI=10.1161/01.res.87.8.670; RA Fernandez-Patron C., Stewart K.G., Zhang Y., Koivunen E., Radomski M.W., RA Davidge S.T.; RT "Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene- RT related peptide promotes vasoconstriction."; RL Circ. Res. 87:670-676(2000). RN [16] RP FUNCTION OF PEX, TISSUE SPECIFICITY, AND INTERACTION WITH TIMP2. RX PubMed=11751392; RA Bello L., Lucini V., Carrabba G., Giussani C., Machluf M., Pluderi M., RA Nikas D., Zhang J., Tomei G., Villani R.M., Carroll R.S., Bikfalvi A., RA Black P.M.; RT "Simultaneous inhibition of glioma angiogenesis, cell proliferation, and RT invasion by a naturally occurring fragment of human metalloproteinase-2."; RL Cancer Res. 61:8730-8736(2001). RN [17] RP ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. 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 [18] RP IDENTIFICATION OF RECEPTOR, INTERACTION WITH TMP2, AND FUNCTION. RX PubMed=11710594; DOI=10.1007/s004320100271; RA Chattopadhyay N., Mitra A., Frei E., Chatterjee A.; RT "Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has RT associated matrix metalloproteinase (MMP-2) activity."; RL J. Cancer Res. Clin. Oncol. 127:653-658(2001). RN [19] RP FUNCTION IN THE FORMATION OF THE FIBROVASCULAR TISSUES. RX PubMed=12714657; DOI=10.1167/iovs.02-0662; RA Noda K., Ishida S., Inoue M., Obata K., Oguchi Y., Okada Y., Ikeda E.; RT "Production and activation of matrix metalloproteinase-2 in proliferative RT diabetic retinopathy."; RL Invest. Ophthalmol. Vis. Sci. 44:2163-2170(2003). RN [20] RP 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 [21] RP SUBCELLULAR LOCATION. RX PubMed=14766804; DOI=10.1096/fj.02-1202fje; RA Kwan J.A., Schulze C.J., Wang W., Leon H., Sariahmetoglu M., Sung M., RA Sawicka J., Sims D.E., Sawicki G., Schulz R.; RT "Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac RT myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in RT vitro."; RL FASEB J. 18:690-692(2004). RN [22] RP PHOSPHORYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17435175; DOI=10.1096/fj.06-7938com; RA Sariahmetoglu M., Crawford B.D., Leon H., Sawicka J., Li L., RA Ballermann B.J., Holmes C., Berthiaume L.G., Holt A., Sawicki G., RA Schulz R.; RT "Regulation of matrix metalloproteinase-2 (MMP-2) activity by RT phosphorylation."; RL FASEB J. 21:2486-2495(2007). RN [23] RP INTERACTION WITH GSK3B, AND FUNCTION. RX PubMed=19493954; DOI=10.1093/cvr/cvp175; RA Kandasamy A.D., Schulz R.; RT "Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 RT mediated proteolysis in cardiomyoblasts."; RL Cardiovasc. Res. 83:698-706(2009). RN [24] RP INDUCTION. RX PubMed=18971601; DOI=10.1159/000166183; RA Hua Y., Xue J., Sun F., Zhu L., Xie M.; RT "Aspirin inhibits MMP-2 and MMP-9 expressions and activities through RT upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDL- RT stimulated macrophages derived from human monocytes."; RL Pharmacology 83:18-25(2009). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P., RA Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [26] RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22509276; DOI=10.1371/journal.pone.0034177; RA Lovett D.H., Mahimkar R., Raffai R.L., Cape L., Maklashina E., Cecchini G., RA Karliner J.S.; RT "A novel intracellular isoform of matrix metalloproteinase-2 induced by RT oxidative stress activates innate immunity."; RL PLoS ONE 7:E34177-E34177(2012). RN [27] {ECO:0007744|PDB:1GEN} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 443-660, AND DISULFIDE BONDS. RX PubMed=7583664; DOI=10.1038/nsb1195-938; RA Libson A.M., Gittis A.G., Collier I.E., Marmer B.L., Goldberg G.I., RA Lattman E.E.; RT "Crystal structure of the haemopexin-like C-terminal domain of gelatinase RT A."; RL Nat. Struct. Biol. 2:938-942(1995). RN [28] {ECO:0007744|PDB:1RTG} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 451-660 IN COMPLEX WITH CALCIUM, RP COFACTOR, AND DISULFIDE BONDS. RX PubMed=8549817; DOI=10.1016/0014-5793(95)01435-7; RA Gohlke U., Gomis-Rueth F.-X., Crabbe T., Murphy G., Docherty A.J., Bode W.; RT "The C-terminal (haemopexin-like) domain structure of human gelatinase A RT (MMP2): structural implications for its function."; RL FEBS Lett. 378:126-130(1996). RN [29] {ECO:0007744|PDB:1CK7} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-660 OF MUTANT ALA-404 IN RP COMPLEX WITH CALCIUM AND ZINC IONS, ACTIVE SITE, COFACTOR, AND DISULFIDE RP BONDS. RX PubMed=10356396; DOI=10.1126/science.284.5420.1667; RA Morgunova E., Tuuttila A., Bergmann U., Isupov M., Lindqvist Y., RA Schneider G., Tryggvason K.; RT "Structure of human pro-matrix metalloproteinase-2: activation mechanism RT revealed."; RL Science 284:1667-1670(1999). RN [30] {ECO:0007744|PDB:1CXW} RP STRUCTURE BY NMR OF 278-336, AND DISULFIDE BONDS. RX PubMed=10545322; DOI=10.1016/s0969-2126(00)80057-x; RA Briknarova K., Grishaev A., Banyai L., Tordai H., Patthy L., Llinas M.; RT "The second type II module from human matrix metalloproteinase 2: RT structure, function and dynamics."; RL Structure 7:1235-1245(1999). RN [31] {ECO:0007744|PDB:1J7M} RP STRUCTURE BY NMR OF 337-394 OF WILD TYPE AND IN COMPLEX WITH PPG PEPTIDES, RP AND DISULFIDE BONDS. RX PubMed=11320090; DOI=10.1074/jbc.m101105200; RA Briknarova K., Gehrmann M., Banyai L., Tordai H., Patthy L., Llinas M.; RT "Gelatin-binding region of human matrix metalloproteinase-2: solution RT structure, dynamics, and function of the COL-23 two-domain construct."; RL J. Biol. Chem. 276:27613-27621(2001). RN [32] {ECO:0007744|PDB:1HOV} RP STRUCTURE BY NMR OF 110-446 IN COMPLEX WITH A HYDROXAMIC ACID INHIBITOR, RP CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=12147339; DOI=10.1016/s0167-4838(02)00307-2; RA Feng Y., Likos J.J., Zhu L., Woodward H., Munie G., McDonald J.J., RA Stevens A.M., Howard C.P., De Crescenzo G.A., Welsch D., Shieh H.S., RA Stallings W.C.; RT "Solution structure and backbone dynamics of the catalytic domain of matrix RT metalloproteinase-2 complexed with a hydroxamic acid inhibitor."; RL Biochim. Biophys. Acta 1598:10-23(2002). RN [33] {ECO:0007744|PDB:1KS0} RP STRUCTURE BY NMR OF 223-282 OF WILD TYPE AND IN COMPLEX WITH A PPG PEPTIDE, RP AND DISULFIDE BONDS. RX PubMed=11928808; DOI=10.1515/bc.2002.014; RA Gehrmann M., Briknarova K., Banyai L., Patthy L., Llinas M.; RT "The col-1 module of human matrix metalloproteinase-2 (MMP-2): RT structural/functional relatedness between gelatin-binding fibronectin type RT II modules and lysine-binding kringle domains."; RL Biol. Chem. 383:137-148(2002). RN [34] {ECO:0007744|PDB:1GXD} RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 30-660 IN COMPLEX WITH CALCIUM; RP ZINC IONS AND INHIBITOR TIMP2, COFACTOR, AND DISULFIDE BONDS. RX PubMed=12032297; DOI=10.1073/pnas.102185399; RA Morgunova E., Tuuttila A., Bergmann U., Tryggvason K.; RT "Structural insight into the complex formation of latent matrix RT metalloproteinase 2 with tissue inhibitor of metalloproteinase 2."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7414-7419(2002). RN [35] {ECO:0007744|PDB:3AYU} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 110-450 IN COMPLEX WITH PEPTIDE RP INHIBITOR; CALCIUM AND ZINC IONS, AND COFACTOR. RX PubMed=21813640; DOI=10.1074/jbc.m111.264176; RA Hashimoto H., Takeuchi T., Komatsu K., Miyazaki K., Sato M., Higashi S.; RT "Structural basis for matrix metalloproteinase-2 (MMP-2)-selective RT inhibitory action of beta-amyloid precursor protein-derived inhibitor."; RL J. Biol. Chem. 286:33236-33243(2011). RN [36] RP VARIANT MONA HIS-101, VARIANT TYR-210, AND CATALYTIC ACTIVITY. RX PubMed=11431697; DOI=10.1038/90100; RA Martignetti J.A., Aqeel A.A., Sewairi W.A., Boumah C.E., Kambouris M., RA Mayouf S.A., Sheth K.V., Eid W.A., Dowling O., Harris J., Glucksman M.J., RA Bahabri S., Meyer B.F., Desnick R.J.; RT "Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a RT multicentric osteolysis and arthritis syndrome."; RL Nat. Genet. 28:261-265(2001). RN [37] RP VARIANT MONA LYS-404. RX PubMed=15691365; DOI=10.1111/j.1399-0004.2004.00402.x; RA Zankl A., Bonafe L., Calcaterra V., Di Rocco M., Superti-Furga A.; RT "Winchester syndrome caused by a homozygous mutation affecting the active RT site of matrix metalloproteinase 2."; RL Clin. Genet. 67:261-266(2005). RN [38] RP VARIANT MONA VAL-400 DEL. RX PubMed=16542393; DOI=10.1111/j.1399-0004.2006.00584.x; RA Rouzier C., Vanatka R., Bannwarth S., Philip N., Coussement A., RA Paquis-Flucklinger V., Lambert J.-C.; RT "A novel homozygous MMP2 mutation in a family with Winchester syndrome."; RL Clin. Genet. 69:271-276(2006). RN [39] RP VARIANTS [LARGE SCALE ANALYSIS] THR-228; MET-498 AND ILE-644. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Ubiquitinous metalloproteinase that is involved in diverse CC functions such as remodeling of the vasculature, angiogenesis, tissue CC repair, tumor invasion, inflammation, and atherosclerotic plaque CC rupture. As well as degrading extracellular matrix proteins, can also CC act on several nonmatrix proteins such as big endothelial 1 and beta- CC type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu CC bond. Appears to have a role in myocardial cell death pathways. CC Contributes to myocardial oxidative stress by regulating the activity CC of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of CC the fibrovascular tissues in association with MMP14. CC -!- FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, posseses CC anti-angiogenic and anti-tumor properties and inhibits cell migration CC and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 CC on the surface of blood vessels. CC -!- FUNCTION: [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and CC initiates a primary innate immune response by inducing mitochondrial- CC nuclear stress signaling with activation of the pro-inflammatory NF- CC kappaB, NFAT and IRF transcriptional pathways. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of gelatin type I and collagen types IV, V, VII, X. CC Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.; CC EC=3.4.24.24; Evidence={ECO:0000305|PubMed:11179305, CC ECO:0000305|PubMed:11431697, ECO:0000305|PubMed:12147339, CC ECO:0000305|PubMed:2834383}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:12147339, CC ECO:0000269|PubMed:21813640, ECO:0000269|PubMed:8549817}; CC Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000269|PubMed:10356396, CC ECO:0000269|PubMed:21813640, ECO:0000269|PubMed:8549817}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:12032297, CC ECO:0000269|PubMed:12147339, ECO:0000269|PubMed:21813640}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:10356396, CC ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640}; CC -!- ACTIVITY REGULATION: Inhibited by histatin-3 1/24 (histatin-5). CC {ECO:0000269|PubMed:11179305}. CC -!- SUBUNIT: Interacts (via the C-terminal hemopexin-like domains- CC containing region) with the integrin alpha-V/beta-3; the interaction CC promotes vascular invasion in angiogenic vessels and melamoma cells. CC Interacts (via the C-terminal PEX domain) with TIMP2 (via the C- CC terminal); the interaction inhibits the degradation activity. Interacts CC with GSK3B. {ECO:0000269|PubMed:11320090, ECO:0000269|PubMed:11710594, CC ECO:0000269|PubMed:11751392, ECO:0000269|PubMed:11928808, CC ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:12147339, CC ECO:0000269|PubMed:1655733, ECO:0000269|PubMed:19493954}. CC -!- INTERACTION: CC P08253; P05067: APP; NbExp=3; IntAct=EBI-1033518, EBI-77613; CC P08253; PRO_0000000092 [P05067]: APP; NbExp=4; IntAct=EBI-1033518, EBI-821758; CC P08253; PRO_0000000093 [P05067]: APP; NbExp=2; IntAct=EBI-1033518, EBI-2431589; CC P08253; P20908: COL5A1; NbExp=3; IntAct=EBI-1033518, EBI-2464511; CC P08253; Q8NBP7: PCSK9; NbExp=4; IntAct=EBI-1033518, EBI-7539251; CC P08253; Q04864-2: REL; NbExp=3; IntAct=EBI-1033518, EBI-10829018; CC P08253; Q8IX30: SCUBE3; NbExp=2; IntAct=EBI-1033518, EBI-4479975; CC P08253; P16035: TIMP2; NbExp=2; IntAct=EBI-1033518, EBI-1033507; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space, CC extracellular matrix {ECO:0000305|PubMed:2834383}. Membrane. Nucleus. CC Note=Colocalizes with integrin alphaV/beta3 at the membrane surface in CC angiogenic blood vessels and melanomas. Found in mitochondria, along CC microfibrils, and in nuclei of cardiomyocytes. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Mitochondrion. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P08253-1; Sequence=Displayed; CC Name=2; CC IsoId=P08253-2; Sequence=VSP_044631; CC Name=3; CC IsoId=P08253-3; Sequence=VSP_045704; CC -!- TISSUE SPECIFICITY: Produced by normal skin fibroblasts. PEX is CC expressed in a number of tumors including gliomas, breast and prostate. CC {ECO:0000269|PubMed:11751392}. CC -!- INDUCTION: Aspirin appears to inhibit expression. CC {ECO:0000269|PubMed:18971601}. 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. CC -!- PTM: Phosphorylation on multiple sites modulates enzymatic activity. CC Phosphorylated by PKC in vitro. {ECO:0000269|PubMed:17435175}. CC -!- PTM: The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT- CC MMP3). Autocatalytic cleavage in the C-terminal produces the anti- CC angiogenic peptide, PEX. This processing appears to be facilitated by CC binding integrinv/beta3. {ECO:0000269|PubMed:12879005, CC ECO:0000269|PubMed:9119036}. CC -!- DISEASE: Multicentric osteolysis, nodulosis, and arthropathy (MONA) CC [MIM:259600]: An autosomal recessive syndrome characterized by severe CC multicentric osteolysis with predominant involvement of the hands and CC feet. Additional features include coarse face, corneal opacities, CC patches of thickened, hyperpigmented skin, hypertrichosis and gum CC hypertrophy. {ECO:0000269|PubMed:11431697, ECO:0000269|PubMed:15691365, CC ECO:0000269|PubMed:16542393}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Induced by oxidative stress. {ECO:0000305}. 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/41396/MMP2"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mmp2/"; 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; M55593; AAA52028.1; -; Genomic_DNA. DR EMBL; M58552; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55582; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55583; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55584; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55585; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55586; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55587; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55588; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55589; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55590; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55591; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; M55592; AAA52028.1; JOINED; Genomic_DNA. DR EMBL; AK301536; BAG63035.1; -; mRNA. DR EMBL; AK310314; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK312711; BAG35588.1; -; mRNA. DR EMBL; AY738117; AAU10089.1; -; Genomic_DNA. DR EMBL; AC007336; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092722; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002576; AAH02576.1; -; mRNA. DR EMBL; M33789; AAA52027.1; -; Genomic_DNA. DR EMBL; J03210; AAA35701.1; -; mRNA. DR CCDS; CCDS10752.1; -. [P08253-1] DR CCDS; CCDS45487.1; -. [P08253-3] DR CCDS; CCDS76869.1; -. [P08253-2] DR PIR; A28153; A28153. DR RefSeq; NP_001121363.1; NM_001127891.2. [P08253-3] DR RefSeq; NP_001289437.1; NM_001302508.1. [P08253-2] DR RefSeq; NP_001289438.1; NM_001302509.1. [P08253-2] DR RefSeq; NP_001289439.1; NM_001302510.1. [P08253-2] DR RefSeq; NP_004521.1; NM_004530.5. [P08253-1] DR PDB; 1CK7; X-ray; 2.80 A; A=30-660. DR PDB; 1CXW; NMR; -; A=278-336. DR PDB; 1EAK; X-ray; 2.66 A; A/B/C/D=32-452. DR PDB; 1GEN; X-ray; 2.15 A; A=443-660. DR PDB; 1GXD; X-ray; 3.10 A; A/B=30-660. DR PDB; 1HOV; NMR; -; A=110-214, A=395-446. DR PDB; 1J7M; NMR; -; A=337-394. DR PDB; 1KS0; NMR; -; A=223-282. DR PDB; 1QIB; X-ray; 2.80 A; A=115-213, A=394-449. DR PDB; 1RTG; X-ray; 2.60 A; A=451-660. DR PDB; 3AYU; X-ray; 2.00 A; A=110-450. DR PDB; 7XGJ; X-ray; 2.80 A; A/B/C=110-450. DR PDB; 7XJO; X-ray; 2.00 A; A/B=110-450. DR PDB; 8H78; X-ray; 2.40 A; A/B=110-450. DR PDBsum; 1CK7; -. DR PDBsum; 1CXW; -. DR PDBsum; 1EAK; -. DR PDBsum; 1GEN; -. DR PDBsum; 1GXD; -. DR PDBsum; 1HOV; -. DR PDBsum; 1J7M; -. DR PDBsum; 1KS0; -. DR PDBsum; 1QIB; -. DR PDBsum; 1RTG; -. DR PDBsum; 3AYU; -. DR PDBsum; 7XGJ; -. DR PDBsum; 7XJO; -. DR PDBsum; 8H78; -. DR AlphaFoldDB; P08253; -. DR SMR; P08253; -. DR BioGRID; 110457; 61. DR CORUM; P08253; -. DR IntAct; P08253; 41. DR MINT; P08253; -. DR STRING; 9606.ENSP00000219070; -. DR BindingDB; P08253; -. DR ChEMBL; CHEMBL333; -. DR DrugBank; DB05387; AE-941. DR DrugBank; DB01197; Captopril. DR DrugBank; DB06423; Endostatin. DR DrugBank; DB04866; Halofuginone. DR DrugBank; DB00786; Marimastat. DR DrugBank; DB12843; Oleandrin. DR DrugBank; DB01630; SC-74020. DR DrugCentral; P08253; -. DR GuidetoPHARMACOLOGY; 1629; -. DR MEROPS; M10.003; -. DR CarbonylDB; P08253; -. DR GlyCosmos; P08253; 3 sites, 2 glycans. DR GlyGen; P08253; 3 sites, 2 O-linked glycans (1 site). DR iPTMnet; P08253; -. DR PhosphoSitePlus; P08253; -. DR BioMuta; MMP2; -. DR DMDM; 116856; -. DR CPTAC; non-CPTAC-2615; -. DR EPD; P08253; -. DR jPOST; P08253; -. DR MassIVE; P08253; -. DR MaxQB; P08253; -. DR PaxDb; 9606-ENSP00000219070; -. DR PeptideAtlas; P08253; -. DR ProteomicsDB; 19808; -. DR ProteomicsDB; 52101; -. [P08253-1] DR ProteomicsDB; 5336; -. DR ABCD; P08253; 2 sequenced antibodies. DR Antibodypedia; 773; 1942 antibodies from 52 providers. DR DNASU; 4313; -. DR Ensembl; ENST00000219070.9; ENSP00000219070.4; ENSG00000087245.13. [P08253-1] DR Ensembl; ENST00000437642.6; ENSP00000394237.2; ENSG00000087245.13. [P08253-3] DR Ensembl; ENST00000543485.5; ENSP00000444143.1; ENSG00000087245.13. [P08253-2] DR Ensembl; ENST00000570308.5; ENSP00000461421.1; ENSG00000087245.13. [P08253-2] DR GeneID; 4313; -. DR KEGG; hsa:4313; -. DR MANE-Select; ENST00000219070.9; ENSP00000219070.4; NM_004530.6; NP_004521.1. DR UCSC; uc002ehz.5; human. [P08253-1] DR AGR; HGNC:7166; -. DR CTD; 4313; -. DR DisGeNET; 4313; -. DR GeneCards; MMP2; -. DR GeneReviews; MMP2; -. DR HGNC; HGNC:7166; MMP2. DR HPA; ENSG00000087245; Tissue enhanced (gallbladder). DR MalaCards; MMP2; -. DR MIM; 120360; gene. DR MIM; 259600; phenotype. DR neXtProt; NX_P08253; -. DR OpenTargets; ENSG00000087245; -. DR Orphanet; 371428; Multicentric osteolysis-nodulosis-arthropathy spectrum. DR PharmGKB; PA30877; -. DR VEuPathDB; HostDB:ENSG00000087245; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000158511; -. DR HOGENOM; CLU_015489_6_2_1; -. DR InParanoid; P08253; -. DR OMA; CPKDSCN; -. DR OrthoDB; 5340816at2759; -. DR PhylomeDB; P08253; -. DR TreeFam; TF315428; -. DR BioCyc; MetaCyc:HS01565-MONOMER; -. DR BRENDA; 3.4.24.24; 2681. DR PathwayCommons; P08253; -. 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-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). 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-9009391; Extra-nuclear estrogen signaling. DR SignaLink; P08253; -. DR SIGNOR; P08253; -. DR BioGRID-ORCS; 4313; 12 hits in 1159 CRISPR screens. DR ChiTaRS; MMP2; human. DR EvolutionaryTrace; P08253; -. DR GeneWiki; MMP2; -. DR GenomeRNAi; 4313; -. DR Pharos; P08253; Tchem. DR PRO; PR:P08253; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P08253; Protein. DR Bgee; ENSG00000087245; Expressed in stromal cell of endometrium and 182 other cell types or tissues. DR ExpressionAtlas; P08253; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0030017; C:sarcomere; IEA:Ensembl. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0001968; F:fibronectin binding; IEA:Ensembl. DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; EXP:Reactome. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0001955; P:blood vessel maturation; IEA:Ensembl. DR GO; GO:0060346; P:bone trabecula formation; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl. 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:ParkinsonsUK-UCL. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0001957; P:intramembranous ossification; IEA:Ensembl. DR GO; GO:0001553; P:luteinization; IEA:Ensembl. DR GO; GO:0048246; P:macrophage chemotaxis; IEA:Ensembl. DR GO; GO:0007162; P:negative regulation of cell adhesion; IEA:Ensembl. DR GO; GO:0045906; P:negative regulation of vasoconstriction; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl. DR GO; GO:0007567; P:parturition; IEA:Ensembl. DR GO; GO:0014012; P:peripheral nervous system axon regeneration; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl. DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; IEA:Ensembl. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:0019538; P:protein metabolic process; TAS:Reactome. DR GO; GO:0006508; P:proteolysis; IDA:ParkinsonsUK-UCL. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:1904645; P:response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0048771; P:tissue remodeling; IBA:GO_Central. 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 IDEAL; IID00296; -. 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:SF29; 72 KDA TYPE IV COLLAGENASE; 1. DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 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; P08253; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Autocatalytic cleavage; KW Calcium; Collagen degradation; Cytoplasm; Direct protein sequencing; KW Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein; KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Mitochondrion; KW Nucleus; Phosphoprotein; Protease; Reference proteome; Repeat; Secreted; KW Signal; Zinc; Zymogen. FT SIGNAL 1..29 FT /evidence="ECO:0000269|PubMed:2834383" FT PROPEP 30..109 FT /note="Activation peptide" FT /id="PRO_0000028714" FT CHAIN 110..660 FT /note="72 kDa type IV collagenase" FT /id="PRO_0000028715" FT CHAIN 445..660 FT /note="PEX" FT /id="PRO_0000391626" FT DOMAIN 228..276 FT /note="Fibronectin type-II 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DOMAIN 286..334 FT /note="Fibronectin type-II 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT DOMAIN 344..392 FT /note="Fibronectin type-II 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479" FT REPEAT 472..516 FT /note="Hemopexin 1" FT REPEAT 517..563 FT /note="Hemopexin 2" FT REPEAT 565..613 FT /note="Hemopexin 3" FT REPEAT 614..660 FT /note="Hemopexin 4" FT REGION 110..221 FT /note="Collagenase-like 1" FT REGION 222..396 FT /note="Collagen-binding" FT REGION 397..465 FT /note="Collagenase-like 2" FT REGION 414..660 FT /note="Required for inhibitor TIMP2 binding" FT /evidence="ECO:0000269|PubMed:1655733" FT MOTIF 100..107 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT ACT_SITE 404 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000305|PubMed:10356396" FT BINDING 102 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1EAK, ECO:0007744|PDB:1GXD" FT BINDING 134 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1QIB, ECO:0007744|PDB:3AYU" FT BINDING 168 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1EAK, ECO:0007744|PDB:3AYU" FT BINDING 178 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:1QIB, FT ECO:0007744|PDB:3AYU" FT BINDING 180 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:1QIB, FT ECO:0007744|PDB:3AYU" FT BINDING 185 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 186 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 193 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:1QIB, FT ECO:0007744|PDB:3AYU" FT BINDING 200 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1EAK, ECO:0007744|PDB:3AYU" FT BINDING 202 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 204 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 206 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:1QIB, FT ECO:0007744|PDB:3AYU" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 209 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1QIB, ECO:0007744|PDB:3AYU" FT BINDING 211 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1QIB, ECO:0007744|PDB:3AYU" FT BINDING 211 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:3AYU" FT BINDING 403 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:3AYU" FT BINDING 407 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:3AYU" FT BINDING 413 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:12032297, ECO:0000269|PubMed:21813640, FT ECO:0007744|PDB:1CK7, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD, ECO:0007744|PDB:3AYU" FT BINDING 476 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:8549817, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1RTG" FT BINDING 521 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:8549817, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1RTG" FT BINDING 569 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:8549817, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1RTG" FT BINDING 618 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:10356396, FT ECO:0000269|PubMed:8549817, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1RTG" FT CARBOHYD 573 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 642 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 233..259 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:11928808, ECO:0000269|PubMed:12032297, FT ECO:0007744|PDB:1EAK, ECO:0007744|PDB:1GXD, FT ECO:0007744|PDB:1KS0" FT DISULFID 247..274 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10545322, ECO:0000269|PubMed:11928808, FT ECO:0007744|PDB:1EAK, ECO:0007744|PDB:1GXD, FT ECO:0007744|PDB:1KS0" FT DISULFID 291..317 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:10545322, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1CXW, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD" FT DISULFID 305..332 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:10545322, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1CXW, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD" FT DISULFID 349..375 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:10545322, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1CXW, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD" FT DISULFID 363..390 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:10545322, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1CXW, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD" FT DISULFID 469..660 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479, FT ECO:0000269|PubMed:10356396, ECO:0000269|PubMed:10545322, FT ECO:0000269|PubMed:12032297, ECO:0007744|PDB:1CK7, FT ECO:0007744|PDB:1CXW, ECO:0007744|PDB:1EAK, FT ECO:0007744|PDB:1GXD" FT VAR_SEQ 1..76 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044631" FT VAR_SEQ 1..51 FT /note="MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAV FT -> M (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045704" FT VARIANT 101 FT /note="R -> H (in MONA; dbSNP:rs121912953)" FT /evidence="ECO:0000269|PubMed:11431697" FT /id="VAR_032423" FT VARIANT 210 FT /note="D -> Y" FT /evidence="ECO:0000269|PubMed:11431697" FT /id="VAR_032424" FT VARIANT 228 FT /note="A -> T (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs759302357)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036136" FT VARIANT 400 FT /note="Missing (in MONA)" FT /evidence="ECO:0000269|PubMed:16542393" FT /id="VAR_054996" FT VARIANT 404 FT /note="E -> K (in MONA; dbSNP:rs121912955)" FT /evidence="ECO:0000269|PubMed:15691365" FT /id="VAR_032425" FT VARIANT 447 FT /note="A -> V (in dbSNP:rs17859943)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020616" FT VARIANT 498 FT /note="T -> M (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs764961297)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036137" FT VARIANT 621 FT /note="V -> L (in dbSNP:rs16955280)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020617" FT VARIANT 644 FT /note="S -> I (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036138" FT CONFLICT 235 FT /note="F -> S (in Ref. 3; AK310314)" FT /evidence="ECO:0000305" FT CONFLICT 546 FT /note="S -> G (in Ref. 3; BAG35588)" FT /evidence="ECO:0000305" FT CONFLICT 618 FT /note="D -> G (in Ref. 3; BAG35588)" FT /evidence="ECO:0000305" FT HELIX 46..56 FT /evidence="ECO:0007829|PDB:1EAK" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:1CK7" FT HELIX 67..80 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:1GXD" FT HELIX 91..97 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:1CK7" FT STRAND 120..128 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:1HOV" FT HELIX 137..152 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 158..161 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 163..165 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 168..174 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 192..195 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:3AYU" FT TURN 200..203 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:1HOV" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:3AYU" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 235..239 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 242..246 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 258..264 FT /evidence="ECO:0007829|PDB:1EAK" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:1EAK" FT TURN 277..279 FT /evidence="ECO:0007829|PDB:1EAK" FT TURN 284..288 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 293..297 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 300..304 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 316..321 FT /evidence="ECO:0007829|PDB:1EAK" FT TURN 323..325 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 329..331 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 338..341 FT /evidence="ECO:0007829|PDB:1GXD" FT TURN 342..346 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 358..362 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 374..379 FT /evidence="ECO:0007829|PDB:1EAK" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:1EAK" FT STRAND 394..396 FT /evidence="ECO:0007829|PDB:3AYU" FT HELIX 397..408 FT /evidence="ECO:0007829|PDB:3AYU" FT STRAND 422..424 FT /evidence="ECO:0007829|PDB:3AYU" FT HELIX 435..445 FT /evidence="ECO:0007829|PDB:3AYU" FT TURN 468..470 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 476..481 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 484..489 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 492..498 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 504..508 FT /evidence="ECO:0007829|PDB:1GEN" FT HELIX 509..511 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 514..516 FT /evidence="ECO:0007829|PDB:1GXD" FT STRAND 521..526 FT /evidence="ECO:0007829|PDB:1GEN" FT TURN 527..530 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 531..536 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 539..544 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 553..555 FT /evidence="ECO:0007829|PDB:1GEN" FT HELIX 556..559 FT /evidence="ECO:0007829|PDB:1GEN" FT TURN 563..566 FT /evidence="ECO:0007829|PDB:1GXD" FT STRAND 569..573 FT /evidence="ECO:0007829|PDB:1GEN" FT TURN 575..577 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 580..584 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 587..592 FT /evidence="ECO:0007829|PDB:1GEN" FT TURN 593..596 FT /evidence="ECO:0007829|PDB:1GEN" FT HELIX 606..609 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 610..612 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 618..622 FT /evidence="ECO:0007829|PDB:1GEN" FT TURN 624..626 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 628..633 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 636..641 FT /evidence="ECO:0007829|PDB:1GEN" FT STRAND 644..652 FT /evidence="ECO:0007829|PDB:1GEN" FT HELIX 653..656 FT /evidence="ECO:0007829|PDB:1GEN" SQ SEQUENCE 660 AA; 73882 MW; BC7147DC8B49F289 CRC64; MEALMARGAL TGPLRALCLL GCLLSHAAAA PSPIIKFPGD VAPKTDKELA VQYLNTFYGC PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARAFQV WSDVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GKEYNSCTDT GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNAEGQP CKFPFRFQGT SYDSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV FPFTFLGNKY ESCTSAGRSD GKMWCATTAN YDDDRKWGFC PDQGYSLFLV AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSQDDIKG IQELYGASPD IDLGTGPTPT LGPVTPEICK QDIVFDGIAQ IRGEIFFFKD RFIWRTVTPR DKPMGPLLVA TFWPELPEKI DAVYEAPQEE KAVFFAGNEY WIYSASTLER GYPKPLTSLG LPPDVQRVDA AFNWSKNKKT YIFAGDKFWR YNEVKKKMDP GFPKLIADAW NAIPDNLDAV VDLQGGGHSY FFKGAYYLKL ENQSLKSVKF GSIKSDWLGC //