MMP3_HUMAN
ID MMP3_HUMAN Reviewed; 477 AA.
AC P08254; B2R8B8; Q3B7S0; Q6GRF8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Stromelysin-1;
DE Short=SL-1;
DE EC=3.4.24.17;
DE AltName: Full=Matrix metalloproteinase-3;
DE Short=MMP-3;
DE AltName: Full=Transin-1;
DE Flags: Precursor;
GN Name=MMP3; Synonyms=STMY1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 18-24.
RX PubMed=3360803; DOI=10.1016/s0021-9258(18)68705-8;
RA Saus J., Quinones S., Otani Y., Nagase H., Harris E.D. Jr., Kurkinen M.;
RT "The complete primary structure of human matrix metalloproteinase-3.
RT Identity with stromelysin.";
RL J. Biol. Chem. 263:6742-6745(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=3030290; DOI=10.1042/bj2400913;
RA Whitham S.E., Murphy G., Angel P., Rahmsdorf H.J., Smith B., Lyons A.,
RA Harris T.J.R., Reynolds J.J., Herrlich P., Docherty A.J.P.;
RT "Comparison of human stromelysin and collagenase by cloning and sequence
RT analysis.";
RL Biochem. J. 240:913-916(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3477804; DOI=10.1073/pnas.84.19.6725;
RA Wilhelm S.M., Collier I.E., Kronberger A., Eisen A.Z., Marmer B.L.,
RA Grant G.A., Bauer E.A., Goldberg G.I.;
RT "Human skin fibroblast stromelysin: structure, glycosylation, substrate
RT specificity, and differential expression in normal and tumorigenic cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6725-6729(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lin D., Duncan M., Allen E., Araujo R., Aparicio A., Chai A., Chung E.,
RA Davis K., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O.,
RA Lashkari D., Lew H., Namath A., Oefner P., Roberts D., Heller R.,
RA Davis R.W.;
RT "Three matrix metalloproteinases on 81kb of P1 insert.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-45.
RC TISSUE=Synovium;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-45.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-45.
RC TISSUE=Lung;
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 [10]
RP ZYMOGEN ACTIVATION.
RX PubMed=2383557; DOI=10.1021/bi00476a020;
RA Nagase H., Enghild J.J., Suzuki K., Salvesen G.;
RT "Stepwise activation mechanisms of the precursor of matrix
RT metalloproteinase 3 (stromelysin) by proteinases and (4-
RT aminophenyl)mercuric acetate.";
RL Biochemistry 29:5783-5789(1990).
RN [11]
RP INVOLVEMENT IN CHDS6.
RX PubMed=8662692; DOI=10.1074/jbc.271.22.13244;
RA Ye S., Eriksson P., Hamsten A., Kurkinen M., Humphries S.E., Henney A.M.;
RT "Progression of coronary atherosclerosis is associated with a common
RT genetic variant of the human stromelysin-1 promoter which results in
RT reduced gene expression.";
RL J. Biol. Chem. 271:13055-13060(1996).
RN [12]
RP INVOLVEMENT IN CHDS6.
RX PubMed=12477941; DOI=10.1056/nejmoa021445;
RA Yamada Y., Izawa H., Ichihara S., Takatsu F., Ishihara H., Hirayama H.,
RA Sone T., Tanaka M., Yokota M.;
RT "Prediction of the risk of myocardial infarction from polymorphisms in
RT candidate genes.";
RL N. Engl. J. Med. 347:1916-1923(2002).
RN [13]
RP STRUCTURE BY NMR OF CATALYTIC DOMAIN.
RX PubMed=7656014; DOI=10.1038/nsb0294-111;
RA Gooley P.R., O'Connell J.F., Marcy A.I., Cuca G.C., Salowe S.P., Bush B.L.,
RA Hermes J.D., Esser C.K., Hagmann W.K., Springer J.P., Johnson B.A.;
RT "The NMR structure of the inhibited catalytic domain of human stromelysin-
RT 1.";
RL Nat. Struct. Biol. 1:111-118(1994).
RN [14]
RP STRUCTURE BY NMR OF 100-267.
RX PubMed=9827994; DOI=10.1002/pro.5560071105;
RA Stockman B.J., Waldon D.J., Gates J.A., Scahill T.A., Kloosterman D.A.,
RA Mizsak S.A., Jacobsen E.J., Belonga K.L., Mitchell M.A., Mao B.,
RA Petke J.D., Goodman L., Powers E.A., Ledbetter S.R., Kaytes P.S.,
RA Vogeli G., Marshall V.P., Petzold G.L., Poorman R.A.;
RT "Solution structures of stromelysin complexed to thiadiazole inhibitors.";
RL Protein Sci. 7:2281-2286(1998).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 18-272.
RX PubMed=8535233; DOI=10.1002/pro.5560041002;
RA Becker J.W., Marcy A.I., Rokosz L.L., Axel M.G., Burbaum J.J.,
RA Fitzgerald P.M.D., Cameron P.M., Esser C.K., Hagmann W.K., Hermes J.D.,
RA Springer J.P.;
RT "Stromelysin-1: three-dimensional structure of the inhibited catalytic
RT domain and of the C-truncated proenzyme.";
RL Protein Sci. 4:1966-1976(1995).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-266.
RX PubMed=8740360; DOI=10.1016/s0969-2126(96)00043-3;
RA Dhanaraj V., Ye Q.-Z., Johnson L.L., Hupe D.J., Otwine D.F.,
RA Dunbar J.B. Jr., Rubin J.R., Pavlovsky A., Humblet C., Blundell T.L.;
RT "X-ray structure of a hydroxamate inhibitor complex of stromelysin
RT catalytic domain and its comparison with members of the zinc
RT metalloproteinase superfamily.";
RL Structure 4:375-386(1996).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 105-264.
RX PubMed=9083493; DOI=10.1021/jm960465t;
RA Esser C.K., Bugianesi R.L., Caldwell C.G., Chapman K.T., Durette P.L.,
RA Girotra N.N., Kopka I.E., Lanza T.J., Levorse D.A., Maccoss M., Owens K.A.,
RA Ponpipom M.M., Simeone J.P., Harrison R.K., Niedzwiecki L., Becker J.W.,
RA Marcy A.I., Axel M.G., Christen A.J., McDonnell J., Moore V.L.,
RA Olszewski J.M., Saphos C., Visco D.M., Shen F., Colletti A., Kriter P.A.,
RA Hagmann W.K.;
RT "Inhibition of stromelysin-1 (MMP-3) by P1'-biphenylylethyl carboxyalkyl
RT dipeptides.";
RL J. Med. Chem. 40:1026-1040(1997).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 100-267 IN COMPLEX WITH TIMP1.
RX PubMed=9288970; DOI=10.1038/37995;
RA Gomis-Rueth F.-X., Maskos K., Betz M., Bergner A., Huber R., Suzuki K.,
RA Yoshida N., Nagase H., Brew K., Bourenkov G.P., Bartunik H., Bode W.;
RT "Mechanism of inhibition of the human matrix metalloproteinase stromelysin-
RT 1 by TIMP-1.";
RL Nature 389:77-81(1997).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 100-264.
RX PubMed=9792098; DOI=10.1002/pro.5560071008;
RA Finzel B.C., Baldwin E.T., Bryant G.L. Jr., Hess G.F., Wilks J.W.,
RA Trepod C.M., Mott J.E., Marshall V.P., Petzold G.L., Poorman R.A.,
RA O'Sullivan T.J., Schostarez H.J., Mitchell M.A.;
RT "Structural characterizations of nonpeptidic thiadiazole inhibitors of
RT matrix metalloproteinases reveal the basis for stromelysin selectivity.";
RL Protein Sci. 7:2118-2126(1998).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-272.
RX PubMed=10543949; DOI=10.1006/jmbi.1999.3147;
RA Chen L., Rydel T.J., Gu F., Dunaway C.M., Pikul S., Dunham K.M.,
RA Barnett B.L.;
RT "Crystal structure of the stromelysin catalytic domain at 2.0-A resolution:
RT inhibitor-induced conformational changes.";
RL J. Mol. Biol. 293:545-557(1999).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 100-267.
RX PubMed=10422833; DOI=10.1110/ps.8.7.1455;
RA Pavlovsky A.G., Williams M.G., Ye Q.-Z., Ortwine D.F., Purchase C.F. II,
RA White A.D., Dhanaraj V., Roth B.D., Johnson L.L., Hupe D., Humblet C.,
RA Blundell T.L.;
RT "X-ray structure of human stromelysin catalytic domain complexed with
RT nonpeptide inhibitors: implications for inhibitor selectivity.";
RL Protein Sci. 8:1455-1462(1999).
RN [22]
RP STRUCTURE BY NMR OF 100-272.
RX PubMed=9760240; DOI=10.1021/bi981328w;
RA Li Y.C., Zhang X., Melton R., Ganu V., Gonnella N.C.;
RT "Solution structure of the catalytic domain of human stromelysin-1
RT complexed to a potent, nonpeptidic inhibitor.";
RL Biochemistry 37:14048-14056(1998).
CC -!- FUNCTION: Can degrade fibronectin, laminin, gelatins of type I, III,
CC IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans.
CC Activates procollagenase.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage where P1', P2' and P3' are hydrophobic
CC residues.; EC=3.4.24.17;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 4 Ca(2+) ions per subunit.;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 2 Zn(2+) ions per subunit.;
CC -!- INTERACTION:
CC P08254; P50222: MEOX2; NbExp=3; IntAct=EBI-6957351, EBI-748397;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305}.
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 -!- DISEASE: Coronary heart disease 6 (CHDS6) [MIM:614466]: A
CC multifactorial disease characterized by an imbalance between myocardial
CC functional requirements and the capacity of the coronary vessels to
CC supply sufficient blood flow. Decreased capacity of the coronary
CC vessels is often associated with thickening and loss of elasticity of
CC the coronary arteries. {ECO:0000269|PubMed:12477941,
CC ECO:0000269|PubMed:8662692}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. A
CC polymorphism in the MMP3 promoter region is associated with the risk of
CC coronary heart disease and myocardial infarction, due to lower MMP3
CC proteolytic activity and higher extracellular matrix deposition in
CC atherosclerotic lesions.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/mmp3/";
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DR EMBL; X05232; CAA28859.1; -; mRNA.
DR EMBL; J03209; AAA36321.1; -; mRNA.
DR EMBL; U78045; AAB36942.1; -; Genomic_DNA.
DR EMBL; AK223283; BAD97003.1; -; mRNA.
DR EMBL; AK223291; BAD97011.1; -; mRNA.
DR EMBL; AK313310; BAG36115.1; -; mRNA.
DR EMBL; AF405705; AAK95247.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67032.1; -; Genomic_DNA.
DR EMBL; BC069676; AAH69676.1; -; mRNA.
DR EMBL; BC069716; AAH69716.1; -; mRNA.
DR EMBL; BC074815; AAH74815.1; -; mRNA.
DR EMBL; BC074869; AAH74869.1; -; mRNA.
DR EMBL; BC105954; AAI05955.1; -; mRNA.
DR EMBL; BC107490; AAI07491.1; -; mRNA.
DR EMBL; BC107491; AAI07492.1; -; mRNA.
DR CCDS; CCDS8323.1; -.
DR PIR; A28156; KCHUS1.
DR RefSeq; NP_002413.1; NM_002422.4.
DR PDB; 1B3D; X-ray; 2.30 A; A/B=100-272.
DR PDB; 1B8Y; X-ray; 2.00 A; A=100-266.
DR PDB; 1BIW; X-ray; 2.50 A; A/B=100-272.
DR PDB; 1BM6; NMR; -; A=100-272.
DR PDB; 1BQO; X-ray; 2.30 A; A/B=100-272.
DR PDB; 1C3I; X-ray; 1.83 A; A/B=100-272.
DR PDB; 1C8T; X-ray; 2.60 A; A/B=103-268.
DR PDB; 1CAQ; X-ray; 1.80 A; A=100-267.
DR PDB; 1CIZ; X-ray; 1.64 A; A=100-267.
DR PDB; 1CQR; X-ray; 2.00 A; A/B=100-272.
DR PDB; 1D5J; X-ray; 2.60 A; A/B=100-272.
DR PDB; 1D7X; X-ray; 2.00 A; A/B=100-272.
DR PDB; 1D8F; X-ray; 2.40 A; A/B=100-272.
DR PDB; 1D8M; X-ray; 2.44 A; A/B=100-272.
DR PDB; 1G05; X-ray; 2.45 A; A/B=100-272.
DR PDB; 1G49; X-ray; 1.90 A; A/B=100-272.
DR PDB; 1G4K; X-ray; 2.00 A; A/B/C=100-267.
DR PDB; 1HFS; X-ray; 1.70 A; A=105-264.
DR PDB; 1HY7; X-ray; 1.50 A; A/B=100-272.
DR PDB; 1OO9; NMR; -; A=100-267.
DR PDB; 1QIA; X-ray; 2.00 A; A/B/C/D=106-267.
DR PDB; 1QIC; X-ray; 2.00 A; A/B/C/D=106-266.
DR PDB; 1SLM; X-ray; 1.90 A; A=18-272.
DR PDB; 1SLN; X-ray; 2.27 A; A=100-272.
DR PDB; 1UEA; X-ray; 2.80 A; A/C=100-272.
DR PDB; 1UMS; NMR; -; A=100-273.
DR PDB; 1UMT; NMR; -; A=100-273.
DR PDB; 1USN; X-ray; 1.80 A; A=100-264.
DR PDB; 2D1O; X-ray; 2.02 A; A/B=100-270.
DR PDB; 2JNP; NMR; -; A=105-265.
DR PDB; 2JT5; NMR; -; A=105-265.
DR PDB; 2JT6; NMR; -; A=105-265.
DR PDB; 2SRT; NMR; -; A=100-272.
DR PDB; 2USN; X-ray; 2.20 A; A=100-264.
DR PDB; 3OHL; X-ray; 2.36 A; A=100-266.
DR PDB; 3OHO; X-ray; 2.50 A; A=100-268.
DR PDB; 3USN; NMR; -; A=100-267.
DR PDB; 4DPE; X-ray; 1.96 A; A/B=100-272.
DR PDB; 4G9L; X-ray; 1.88 A; A/B=100-272.
DR PDB; 4JA1; X-ray; 1.96 A; A/B=100-272.
DR PDB; 6MAV; X-ray; 2.37 A; A=100-267.
DR PDB; 6N9D; X-ray; 2.67 A; A=100-264.
DR PDB; 7S7L; X-ray; 2.34 A; A=100-272.
DR PDB; 7S7M; X-ray; 3.00 A; A=100-272.
DR PDBsum; 1B3D; -.
DR PDBsum; 1B8Y; -.
DR PDBsum; 1BIW; -.
DR PDBsum; 1BM6; -.
DR PDBsum; 1BQO; -.
DR PDBsum; 1C3I; -.
DR PDBsum; 1C8T; -.
DR PDBsum; 1CAQ; -.
DR PDBsum; 1CIZ; -.
DR PDBsum; 1CQR; -.
DR PDBsum; 1D5J; -.
DR PDBsum; 1D7X; -.
DR PDBsum; 1D8F; -.
DR PDBsum; 1D8M; -.
DR PDBsum; 1G05; -.
DR PDBsum; 1G49; -.
DR PDBsum; 1G4K; -.
DR PDBsum; 1HFS; -.
DR PDBsum; 1HY7; -.
DR PDBsum; 1OO9; -.
DR PDBsum; 1QIA; -.
DR PDBsum; 1QIC; -.
DR PDBsum; 1SLM; -.
DR PDBsum; 1SLN; -.
DR PDBsum; 1UEA; -.
DR PDBsum; 1UMS; -.
DR PDBsum; 1UMT; -.
DR PDBsum; 1USN; -.
DR PDBsum; 2D1O; -.
DR PDBsum; 2JNP; -.
DR PDBsum; 2JT5; -.
DR PDBsum; 2JT6; -.
DR PDBsum; 2SRT; -.
DR PDBsum; 2USN; -.
DR PDBsum; 3OHL; -.
DR PDBsum; 3OHO; -.
DR PDBsum; 3USN; -.
DR PDBsum; 4DPE; -.
DR PDBsum; 4G9L; -.
DR PDBsum; 4JA1; -.
DR PDBsum; 6MAV; -.
DR PDBsum; 6N9D; -.
DR PDBsum; 7S7L; -.
DR PDBsum; 7S7M; -.
DR AlphaFoldDB; P08254; -.
DR BMRB; P08254; -.
DR SMR; P08254; -.
DR BioGRID; 110458; 19.
DR IntAct; P08254; 8.
DR MINT; P08254; -.
DR STRING; 9606.ENSP00000299855; -.
DR BindingDB; P08254; -.
DR ChEMBL; CHEMBL283; -.
DR DrugBank; DB02367; (1n)-4-N-Butoxyphenylsulfonyl-(2r)-N-Hydroxycarboxamido-(4s)-Methanesulfonylamino-Pyrrolidine.
DR DrugBank; DB04140; 1-Benzyl-3-(4-Methoxy-Benzenesulfonyl)-6-Oxo-Hexahydro-Pyrimidine-4-Carboxylic Acid Hydroxyamide.
DR DrugBank; DB08643; 2-(2-{2-[(BIPHENYL-4-YLMETHYL)-AMINO]-3-MERCAPTO-PENTANOYLAMINO}-ACETYLAMINO)-3-METHYL-BUTYRIC ACID METHYL ESTER.
DR DrugBank; DB07390; 2-[3-(5-Mercapto-[1,3,4]thiadiazol-2-yl)-ureido]-N-methyl-3-phenyl-propionamide.
DR DrugBank; DB07988; 2-[3-(5-Mercapto-[1,3,4]thiadiazol-2yl)-ureido]-N-methyl-3-pentafluorophenyl-propionamide.
DR DrugBank; DB02449; 3-(1h-Indol-3-Yl)-2-[4-(4-Phenyl-Piperidin-1-Yl)-Benzenesulfonylamino]-Propionic Acid.
DR DrugBank; DB08030; 3-[(4'-cyanobiphenyl-4-yl)oxy]-N-hydroxypropanamide.
DR DrugBank; DB01996; 3-Methylpyridine.
DR DrugBank; DB03033; 4-methoxybenzenesulfinate.
DR DrugBank; DB03368; 5-Methyl-5-(4-Phenoxy-Phenyl)-Pyrimidine-2,4,6-Trione.
DR DrugBank; DB07987; [2-(5-Mercapto-[1,3,4]thiadiazol-2-ylcarbamoyl)-1-phenyl-ethyl]-carbamic acid benzyl ester.
DR DrugBank; DB07986; [4-(4-PHENYL-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-ACETIC ACID.
DR DrugBank; DB02090; A Disubstituted Succinyl Caprolactam Hydroxymate Mmp3inhibitor.
DR DrugBank; DB02697; Hydroxyaminovaline.
DR DrugBank; DB00786; Marimastat.
DR DrugBank; DB08507; N-[[2-METHYL-4-HYDROXYCARBAMOYL]BUT-4-YL-N]-BENZYL-P-[PHENYL]-P-[METHYL]PHOSPHINAMID.
DR DrugBank; DB01877; N-Hydroxy 1n(4-Methoxyphenyl)Sulfonyl-4-(Z,E-N-Methoxyimino)Pyrrolidine-2r-Carboxamide.
DR DrugBank; DB04232; N-Hydroxy-1-(4-Methoxyphenyl)Sulfonyl-4-Benzyloxycarbonyl-Piperazine-2-Carboxamide.
DR DrugBank; DB02350; N-Hydroxy-4-[(4-Methoxylphenyl)Sulfonyl]-2,2-Dimethyl-Hexahydro-1,4-Thiazepine-3(S)-Carboxamide.
DR DrugBank; DB08271; N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID.
DR DrugBank; DB08029; N~2~-(biphenyl-4-ylsulfonyl)-N-hydroxy-N~2~-(2-hydroxyethyl)glycinamide.
DR DrugBank; DB04416; R-2-{[4'-Methoxy-(1,1'-Biphenyl)-4-Yl]-Sulfonyl}-Amino-6-Methoxy-Hex-4-Ynoic Acid.
DR DrugCentral; P08254; -.
DR GuidetoPHARMACOLOGY; 1630; -.
DR MEROPS; M10.005; -.
DR GlyGen; P08254; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P08254; -.
DR PhosphoSitePlus; P08254; -.
DR BioMuta; MMP3; -.
DR DMDM; 116857; -.
DR EPD; P08254; -.
DR jPOST; P08254; -.
DR MassIVE; P08254; -.
DR PaxDb; P08254; -.
DR PeptideAtlas; P08254; -.
DR PRIDE; P08254; -.
DR ProteomicsDB; 52102; -.
DR ABCD; P08254; 1 sequenced antibody.
DR Antibodypedia; 1509; 1393 antibodies from 50 providers.
DR DNASU; 4314; -.
DR Ensembl; ENST00000299855.10; ENSP00000299855.5; ENSG00000149968.12.
DR GeneID; 4314; -.
DR KEGG; hsa:4314; -.
DR MANE-Select; ENST00000299855.10; ENSP00000299855.5; NM_002422.5; NP_002413.1.
DR UCSC; uc001phj.2; human.
DR CTD; 4314; -.
DR DisGeNET; 4314; -.
DR GeneCards; MMP3; -.
DR HGNC; HGNC:7173; MMP3.
DR HPA; ENSG00000149968; Tissue enriched (salivary).
DR MalaCards; MMP3; -.
DR MIM; 185250; gene.
DR MIM; 614466; phenotype.
DR neXtProt; NX_P08254; -.
DR OpenTargets; ENSG00000149968; -.
DR PharmGKB; PA30886; -.
DR VEuPathDB; HostDB:ENSG00000149968; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000159759; -.
DR HOGENOM; CLU_015489_6_0_1; -.
DR InParanoid; P08254; -.
DR OMA; NFVQQYL; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; P08254; -.
DR TreeFam; TF315428; -.
DR BRENDA; 3.4.24.17; 2681.
DR PathwayCommons; P08254; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR SignaLink; P08254; -.
DR SIGNOR; P08254; -.
DR BioGRID-ORCS; 4314; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; MMP3; human.
DR EvolutionaryTrace; P08254; -.
DR GeneWiki; MMP3; -.
DR GenomeRNAi; 4314; -.
DR Pharos; P08254; Tchem.
DR PRO; PR:P08254; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P08254; protein.
DR Bgee; ENSG00000149968; Expressed in calcaneal tendon and 119 other tissues.
DR ExpressionAtlas; P08254; baseline and differential.
DR Genevisible; P08254; HS.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071732; P:cellular response to nitric oxide; TAS:ParkinsonsUK-UCL.
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:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0010727; P:negative regulation of hydrogen peroxide metabolic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903209; P:positive regulation of oxidative stress-induced cell death; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; TAS:ARUK-UCL.
DR GO; GO:1904645; P:response to amyloid-beta; TAS:ARUK-UCL.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
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; 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 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; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Collagen degradation; Direct protein sequencing;
KW Disulfide bond; Extracellular matrix; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000305|PubMed:3360803"
FT PROPEP 18..99
FT /note="Activation peptide"
FT /id="PRO_0000028728"
FT CHAIN 100..477
FT /note="Stromelysin-1"
FT /id="PRO_0000028729"
FT REPEAT 287..336
FT /note="Hemopexin 1"
FT REPEAT 337..383
FT /note="Hemopexin 2"
FT REPEAT 385..433
FT /note="Hemopexin 3"
FT REPEAT 434..477
FT /note="Hemopexin 4"
FT REGION 262..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 90..97
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 266..287
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 219
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT BINDING 124
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 158
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 196
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT BINDING 218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:8740360"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:8740360"
FT BINDING 228
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:8740360"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 438
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT DISULFID 290..477
FT /evidence="ECO:0000250"
FT VARIANT 45
FT /note="K -> E (in dbSNP:rs679620)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6,
FT ECO:0000269|Ref.7"
FT /id="VAR_013090"
FT CONFLICT 420
FT /note="P -> L (in Ref. 3)"
FT /evidence="ECO:0000305"
FT HELIX 34..41
FT /evidence="ECO:0007829|PDB:1SLM"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:1SLM"
FT HELIX 81..86
FT /evidence="ECO:0007829|PDB:1SLM"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:1SLM"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:1UEA"
FT STRAND 110..118
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1CAQ"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:2SRT"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 158..164
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1HY7"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:2SRT"
FT STRAND 203..211
FT /evidence="ECO:0007829|PDB:1HY7"
FT HELIX 212..223
FT /evidence="ECO:0007829|PDB:1HY7"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4JA1"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1SLM"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:1USN"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:1CIZ"
FT HELIX 253..263
FT /evidence="ECO:0007829|PDB:1HY7"
SQ SEQUENCE 477 AA; 53977 MW; 96194833B907668D CRC64;
MKSLPILLLL CVAVCSAYPL DGAARGEDTS MNLVQKYLEN YYDLKKDVKQ FVRRKDSGPV
VKKIREMQKF LGLEVTGKLD SDTLEVMRKP RCGVPDVGHF RTFPGIPKWR KTHLTYRIVN
YTPDLPKDAV DSAVEKALKV WEEVTPLTFS RLYEGEADIM ISFAVREHGD FYPFDGPGNV
LAHAYAPGPG INGDAHFDDD EQWTKDTTGT NLFLVAAHEI GHSLGLFHSA NTEALMYPLY
HSLTDLTRFR LSQDDINGIQ SLYGPPPDSP ETPLVPTEPV PPEPGTPANC DPALSFDAVS
TLRGEILIFK DRHFWRKSLR KLEPELHLIS SFWPSLPSGV DAAYEVTSKD LVFIFKGNQF
WAIRGNEVRA GYPRGIHTLG FPPTVRKIDA AISDKEKNKT YFFVEDKYWR FDEKRNSMEP
GFPKQIAEDF PGIDSKIDAV FEEFGFFYFF TGSSQLEFDP NAKKVTHTLK SNSWLNC
