| IED ID | IndEnz0002006541 |
| Enzyme Type ID | protease006541 |
| Protein Name |
72 kDa type IV collagenase EC 3.4.24.24 72 kDa gelatinase Gelatinase A Matrix metalloproteinase-2 MMP-2 Cleaved into: PEX |
| Gene Name | Mmp2 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MEARVAWGALAGPLRVLCVLCCLLGRAIAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGCPKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWDKNQITYRIIGYTPDLDPETVDDAFARALKVWSDVTPLRFSRIHDGEADIMINFGRWEHGDGYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFNGREYSSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNADGQPCKFPFRFQGTSYNSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKYESCTSAGRNDGKVWCATTTNYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGALMAPIYTYTKNFRLSHDDIKGIQELYGPSPDADTDTGTGPTPTLGPVTPEICKQDIVFDGIAQIRGEIFFFKDRFIWRTVTPRDKPTGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEYWVYSASTLERGYPKPLTSLGLPPDVQQVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDPGFPKLIADSWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC |
| Enzyme Length | 662 |
| Uniprot Accession Number | P33434 |
| Absorption | |
| Active Site | ACT_SITE 404; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.; EC=3.4.24.24; Evidence={ECO:0000250|UniProtKB:P08253}; |
| DNA Binding | |
| EC Number | 3.4.24.24 |
| Enzyme Function | FUNCTION: Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues (By similarity). {ECO:0000250}.; FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-v/beta-3 on the surface of blood vessels (By similarity). {ECO:0000250}.; FUNCTION: [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. {ECO:0000269|PubMed:22509276}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (1); Chain (2); Disulfide bond (7); Domain (3); Glycosylation (2); Metal binding (23); Motif (1); Propeptide (1); Region (5); Repeat (4); Signal peptide (1) |
| Keywords | Alternative splicing;Angiogenesis;Autocatalytic cleavage;Calcium;Collagen degradation;Cytoplasm;Disulfide bond;Extracellular matrix;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Mitochondrion;Nucleus;Phosphoprotein;Protease;Reference proteome;Repeat;Secreted;Signal;Zinc;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space, extracellular matrix {ECO:0000250}. Membrane {ECO:0000250}. Nucleus {ECO:0000250}. Note=Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Mitochondrion. |
| Modified Residue | |
| Post Translational Modification | PTM: Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro (By similarity). {ECO:0000250}.; PTM: The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3) (By similarity). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3 (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..29; /evidence=ECO:0000250|UniProtKB:P33436 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10090151; 10201949; 10215319; 10232461; 10329460; 10419448; 10433819; 10731089; 10801980; 10821760; 10880400; 10949577; 10985432; 11006154; 11025665; 11165481; 11359935; 11566859; 11675412; 11689884; 11718713; 11747814; 11819823; 11865039; 11880357; 11887181; 11891989; 11912494; 11956760; 11970978; 12023034; 12049638; 12193736; 12208863; 12220955; 12237117; 12368215; 12419962; 12453184; 12473670; 12482397; 12506102; 12557216; 12591918; 12735482; 12750313; 12775562; 12805379; 12815621; 12821796; 12842442; 12939223; 12950084; 12963732; 12975354; 14551157; 14561647; 14563686; 14585355; 14638740; 14675176; 1471951; 14729404; 14729463; 14736853; 14993222; 15047130; 15059974; 15064723; 15075248; 15212943; 15220345; 15265790; 15277330; 15343380; 15355971; 15364410; 15474357; 15502710; 15508185; 15522913; 15536133; 15543606; 15545316; 15545515; 15550552; 15572153; 15618213; 15670768; 15670794; 15707406; 15711638; 15734845; 15739229; 15748894; 15760390; 15760903; 15763341; 15805464; 15823918; 15843578; 15862156; 15937097; 16018191; 16047212; 16093645; 16113801; 16141072; 16147977; 16159824; 16183043; 16219541; 16236725; 16244581; 16258061; 16397239; 16428450; 16469749; 16474180; 16505197; 16509766; 16551362; 16556856; 16585265; 16602821; 16607611; 16650610; 16678100; 16680826; 16691565; 16699069; 16785994; 16825197; 16845676; 16847049; 16887049; 16951375; 16959767; 16980344; 17005848; 17008622; 17065436; 17081126; 17082650; 17136358; 17158653; 17210124; 17215487; 17251494; 17283058; 17303760; 17307908; 17322177; 17344928; 17348864; 17349656; 17382917; 17386921; 17400654; 17412577; 17440987; 17442971; 17460063; 17472698; 17475219; 17483344; 17498626; 17561096; 17587297; 17623663; 17623673; 17633135; 17638886; 17641224; 17681721; 17682049; 17692316; 17709990; 17908800; 17960656; 17965409; 17979883; 18003950; 18043506; 18060646; 18069628; 18160708; 18222481; 18264108; 18267097; 18274672; 18303576; 18340378; 18359864; 18364034; 18445063; 18458097; 18472181; 18492766; 18556655; 18559979; 18596727; 18627313; 18639653; 18667463; 18669618; 18704294; 18757369; 18762577; 18817873; 18835790; 18987327; 19010778; 19015235; 19038858; 19038859; 19051246; 19074020; 19092727; 19147652; 19171847; 19180798; 19221044; 19276073; 19287959; 19509016; 19542530; 19578738; 19580633; 19581512; 19594013; 19724919; 19764560; 19780201; 19790245; 19795413; 19795511; 19808257; 19828778; 19884566; 19913533; 19915515; 19940766; 19995958; 20037812; 20056917; 20093499; 20101710; 20107604; 20152179; 20163454; 20165883; 20181883; 20189954; 20215503; 20223936; 20230750; 20232295; 20305284; 20353950; 20375993; 20398633; 20407871; 20441996; 20516072; 20548288; 20551517; 20563750; 20598569; 20616008; 20637190; 20639459; 20679550; 20683677; 20829506; 20839326; 20845081; 20886179; 20934971; 20937816; 20952093; 20956976; 20978081; 21039989; 21041693; 21079048; 21132408; 21135056; 21135236; 21158073; 21179735; 21231833; 21241594; 21267068; 21300023; 21320869; 21334624; 21343160; 21354273; 21376707; 21418186; 21421844; 21454403; 21508260; 21567073; 21611966; 21641389; 21704005; 21750040; 21775118; 21836084; 21837459; 21858843; 21864729; 21865464; 21900575; 21903356; 21904637; 21906275; 21986284; 21986287; 22014525; 22171010; 22238668; 22378877; 22396544; 22464947; 22483803; 22490679; 22521821; 22550139; 22614125; 22688677; 22714107; 22917927; 22932696; 23028104; 23048035; 23089194; 23091646; 23144462; 23225890; 23306080; 23312504; 23322905; 23334579; 23349620; 23354118; 23398532; 23421805; 23465590; 23482328; 23490298; 23509775; 23523587; 23548779; 23664424; 23702312; 23806407; 23811845; 23824573; 23874529; 23884892; 23936390; 23940733; 24006456; 24028490; 24035828; 24095877; 24141049; 24174624; 24176640; 24195673; 24278461; 24291175; 24333535; 24373743; 24375642; 24508733; 24611815; 24631289; 24652381; 24670518; 24694005; 24706882; 24814605; 24905939; 24971735; 25015352; 25149191; 25150065; 25157440; 25193593; 25204377; 25352026; 25361902; 25381636; 25405459; 25469981; 25512019; 25572963; 25574848; 25576870; 25613181; 25636537; 25646300; 25657308; 25703139; 25704809; 25733533; 25770908; 25778400; 25794647; 25820137; 25824133; 25869489; 25920569; 25961753; 25986148; 26133107; 26213293; 26244298; 26318311; 26355684; 26378152; 26390284; 26438731; 26451090; 26471094; 26510894; 26546710; 26567374; 26588471; 26673451; 26881424; 26968737; 26985676; 26989874; 27001612; 27038751; 27164414; 27265328; 27306493; 27363580; 27453531; 27468657; 27601324; 27633994; 27732850; 27831901; 27915985; 27919822; 28053109; 28118605; 28179581; 28223495; 28237967; 28320710; 28331061; 28400434; 28593951; 28611024; 28639940; 28642362; 28666838; 28669039; 28766880; 28800037; 28821434; 28827401; 28883215; 28912710; 28992079; 29016715; 29064547; 29065106; 29158162; 29190653; 29267523; 29322806; 29366755; 29377313; 29415171; 29428733; 29456135; 29567669; 29743679; 29749704; 29803830; 29913136; 30061417; 30135249; 30248101; 30269950; 30283358; 30297691; 30389913; 30503336; 30572657; 30578393; 30676070; 30723388; 30822518; 30993494; 31061823; 31424120; 31434798; 31461499; 31600777; 31634485; 31699373; 31726690; 32067275; 32208990; 32523119; 32591430; 32732898; 32784053; 32825931; 32882513; 33057440; 33470127; 33763067; 33811421; 33871356; 33891967; 33903225; 33929320; 34001241; 34359839; 7626795; 7669731; 7894006; 8015608; 8144618; 8674412; 8743942; 8872958; 9069116; 9087449; 9108368; 9134100; 9278386; 9291579; 9417058; 9500469; 9508784; 9648071; 9658163; 9882504; |
| Motif | MOTIF 100..107; /note=Cysteine switch; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 74,102 |
| Kinetics | |
| Metal Binding | METAL 102; /note=Zinc 1; in inhibited form; /evidence=ECO:0000250|UniProtKB:P08253; METAL 134; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:P08253; METAL 168; /note=Calcium 2; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 178; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P08253; METAL 180; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P08253; METAL 185; /note=Calcium 3; /evidence=ECO:0000250|UniProtKB:P08253; METAL 186; /note=Calcium 3; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 193; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P08253; METAL 200; /note=Calcium 2; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 202; /note=Calcium 2; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 204; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:P08253; METAL 206; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P08253; METAL 208; /note=Calcium 3; /evidence=ECO:0000250|UniProtKB:P08253; METAL 209; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:P08253; METAL 211; /note=Calcium 1; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 211; /note=Calcium 3; /evidence=ECO:0000250|UniProtKB:P08253; METAL 403; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P08253; METAL 407; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P08253; METAL 413; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P08253; METAL 478; /note=Calcium 4; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 523; /note=Calcium 4; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 571; /note=Calcium 4; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253; METAL 620; /note=Calcium 4; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:P08253 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.24; |