MMP2_HUMAN
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 03-AUG-2022, entry version 249.
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="http://atlasgeneticsoncology.org/Genes/MMP2ID41396ch16q13.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp2/";
CC ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; P08253; -.
DR SMR; P08253; -.
DR BioGRID; 110457; 52.
DR CORUM; P08253; -.
DR IntAct; P08253; 40.
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; DB01630; SC-74020.
DR DrugCentral; P08253; -.
DR GuidetoPHARMACOLOGY; 1629; -.
DR MEROPS; M10.003; -.
DR CarbonylDB; P08253; -.
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; P08253; -.
DR PeptideAtlas; P08253; -.
DR PRIDE; P08253; -.
DR ProteomicsDB; 19808; -.
DR ProteomicsDB; 52101; -. [P08253-1]
DR ProteomicsDB; 5336; -.
DR ABCD; P08253; 2 sequenced antibodies.
DR Antibodypedia; 773; 1650 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 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; RNDGFLW; -.
DR OrthoDB; 965164at2759; -.
DR PhylomeDB; P08253; -.
DR TreeFam; TF315428; -.
DR BioCyc; MetaCyc:HS01565-MON; -.
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; 10 hits in 1075 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 180 other tissues.
DR ExpressionAtlas; P08253; baseline and differential.
DR Genevisible; P08253; HS.
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:0007568; P:aging; IEA:Ensembl.
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:0016477; P:cell migration; 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: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:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; 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: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; 2.10.10.10; -; 2.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 2.
DR IDEAL; IID00296; -.
DR InterPro; IPR028708; 72kDa_collagenase.
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; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR PANTHER; PTHR10201:SF29; PTHR10201:SF29; 1.
DR Pfam; PF00040; fn2; 3.
DR Pfam; PF00045; Hemopexin; 4.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00059; FN2; 3.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR SUPFAM; SSF57440; SSF57440; 3.
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; 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
