Stromelysin-1

Details

Name
Stromelysin-1
Synonyms
  • 3.4.24.17
  • Matrix metalloproteinase-3
  • MMP-3
  • SL-1
  • STMY1
  • Transin-1
Gene Name
MMP3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0019064|Stromelysin-1
MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPV
VKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVN
YTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNV
LAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLY
HSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFDAVS
TLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKGNQF
WAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNSMEP
GFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC
Number of residues
477
Molecular Weight
53976.84
Theoretical pI
6.07
GO Classification
Functions
calcium ion binding / endopeptidase activity / metalloendopeptidase activity / zinc ion binding
Processes
cellular response to amino acid stimulus / cellular response to nitric oxide / collagen catabolic process / extracellular matrix disassembly / extracellular matrix organization / negative regulation of hydrogen peroxide metabolic process / positive regulation of oxidative stress-induced cell death / positive regulation of protein oligomerization / proteolysis / regulation of cell migration
Components
extracellular region / extracellular space / proteinaceous extracellular matrix
General Function
Zinc ion binding
Specific Function
Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0019065|Stromelysin-1 (MMP3)
ATGAAGAGTCTTCCAATCCTACTGTTGCTGTGCGTGGCAGTTTGCTCAGCCTATCCATTG
GATGGAGCTGCAAGGGGTGAGGACACCAGCATGAACCTTGTTCAGAAATATCTAGAAAAC
TACTACGACCTCAAAAAAGATGTGAAACAGTTTGTTAGGAGAAAGGACAGTGGTCCTGTT
GTTAAAAAAATCCGAGAAATGCAGAAGTTCCTTGGATTGGAGGTGACGGGGAAGCTGGAC
TCCGACACTCTGGAGGTGATGCGCAAGCCCAGGTGTGGAGTTCCTGATGTTGGTCACTTC
AGAACCTTTCCTGGCATCCCGAAGTGGAGGAAAACCCACCTTACATACAGGATTGTGAAT
TATACACCAGATTTGCCAAAAGATGCTGTTGATTCTGCTGTTGAGAAAGCTCTGAAAGTC
TGGGAAGAGGTGACTCCACTCACATTCTCCAGGCTGTATGAAGGAGAGGCTGATATAATG
ATCTCTTTTGCAGTTAGAGAACATGGAGACTTTTACCCTTTTGATGGACCTGGAAATGTT
TTGGCCCATGCCTATGCCCCTGGGCCAGGGATTAATGGAGATGCCCACTTTGATGATGAT
GAACAATGGACAAAGGATACAACAGGGACCAATTTATTTCTCGTTGCTGCTCATGAAATT
GGCCACTCCCTGGGTCTCTTTCACTCAGCCAACACTGAAGCTTTGATGTACCCACTCTAT
CACTCACTCACAGACCTGACTCGGTTCCGCCTGTCTCAAGATGATATAAATGGCATTCAG
TCCCTCTATGGACCTCCCCCTGACTCCCCTGAGACCCCCCTGGTACCCACGGAACCTGTC
CCTCCAGAACCTGGGACGCCAGCCAACTGTGATCCTGCTTTGTCCTTTGATGCTGTCAGC
ACTCTGAGGGGAGAAATCCTGATCTTTAAAGACAGGCACTTTTGGCGCAAATCCCTCAGG
AAGCTTGAACCTGAATTGCATTTGATCTCTTCATTTTGGCCATCTCTTCCTTCAGGCGTG
GATGCCGCATATGAAGTTACTAGCAAGGACCTCGTTTTCATTTTTAAAGGAAATCAATTC
TGGGCTATCAGAGGAAATGAGGTACGAGCTGGATACCCAAGAGGCATCCACACCCTAGGT
TTCCCTCCAACCGTGAGGAAAATCGATGCAGCCATTTCTGATAAGGAAAAGAACAAAACA
TATTTCTTTGTAGAGGACAAATACTGGAGATTTGATGAGAAGAGAAATTCCATGGAGCCA
GGCTTTCCCAAGCAAATAGCTGAAGACTTTCCAGGGATTGACTCAAAGATTGATGCTGTT
TTTGAAGAATTTGGGTTCTTTTATTTCTTTACTGGATCTTCACAGTTGGAGTTTGACCCA
AATGCAAAGAAAGTGACACACACTTTGAAGAGTAACAGCTGGCTTAATTGTTGA
Chromosome Location
11
Locus
11q22.3
External Identifiers
ResourceLink
UniProtKB IDP08254
UniProtKB Entry NameMMP3_HUMAN
GenBank Protein ID36633
GenBank Gene IDX05232
GenAtlas IDMMP3
HGNC IDHGNC:7173
General References
  1. Saus J, Quinones S, Otani Y, Nagase H, Harris ED Jr, Kurkinen M: The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin. J Biol Chem. 1988 May 15;263(14):6742-5. [PubMed:3360803]
  2. Whitham SE, Murphy G, Angel P, Rahmsdorf HJ, Smith BJ, Lyons A, Harris TJ, Reynolds JJ, Herrlich P, Docherty AJ: Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J. 1986 Dec 15;240(3):913-6. [PubMed:3030290]
  3. Wilhelm SM, Collier IE, Kronberger A, Eisen AZ, Marmer BL, Grant GA, Bauer EA, Goldberg GI: Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6725-9. [PubMed:3477804]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Nagase H, Enghild JJ, Suzuki K, Salvesen G: Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry. 1990 Jun 19;29(24):5783-9. [PubMed:2383557]
  7. Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM: Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem. 1996 May 31;271(22):13055-60. [PubMed:8662692]
  8. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M: Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002 Dec 12;347(24):1916-23. [PubMed:12477941]
  9. Gooley PR, O'Connell JF, Marcy AI, Cuca GC, Salowe SP, Bush BL, Hermes JD, Esser CK, Hagmann WK, Springer JP, et al.: The NMR structure of the inhibited catalytic domain of human stromelysin-1. Nat Struct Biol. 1994 Feb;1(2):111-8. [PubMed:7656014]
  10. Stockman BJ, Waldon DJ, Gates JA, Scahill TA, Kloosterman DA, Mizsak SA, Jacobsen EJ, Belonga KL, Mitchell MA, Mao B, Petke JD, Goodman L, Powers EA, Ledbetter SR, Kaytes PS, Vogeli G, Marshall VP, Petzold GL, Poorman RA: Solution structures of stromelysin complexed to thiadiazole inhibitors. Protein Sci. 1998 Nov;7(11):2281-6. [PubMed:9827994]
  11. Becker JW, Marcy AI, Rokosz LL, Axel MG, Burbaum JJ, Fitzgerald PM, Cameron PM, Esser CK, Hagmann WK, Hermes JD, et al.: Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme. Protein Sci. 1995 Oct;4(10):1966-76. [PubMed:8535233]
  12. Dhanaraj V, Ye QZ, Johnson LL, Hupe DJ, Ortwine DF, Dunbar JB Jr, Rubin JR, Pavlovsky A, Humblet C, Blundell TL: X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily. Structure. 1996 Apr 15;4(4):375-86. [PubMed:8740360]
  13. Esser CK, Bugianesi RL, Caldwell CG, Chapman KT, Durette PL, Girotra NN, Kopka IE, Lanza TJ, Levorse DA, MacCoss M, Owens KA, Ponpipom MM, Simeone JP, Harrison RK, Niedzwiecki L, Becker JW, Marcy AI, Axel MG, Christen AJ, McDonnell J, Moore VL, Olszewski JM, Saphos C, Visco DM, Hagmann WK, et al.: Inhibition of stromelysin-1 (MMP-3) by P1'-biphenylylethyl carboxyalkyl dipeptides. J Med Chem. 1997 Mar 14;40(6):1026-40. [PubMed:9083493]
  14. Gomis-Ruth FX, Maskos K, Betz M, Bergner A, Huber R, Suzuki K, Yoshida N, Nagase H, Brew K, Bourenkov GP, Bartunik H, Bode W: Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature. 1997 Sep 4;389(6646):77-81. [PubMed:9288970]
  15. Finzel BC, Baldwin ET, Bryant GL Jr, Hess GF, Wilks JW, Trepod CM, Mott JE, Marshall VP, Petzold GL, Poorman RA, O'Sullivan TJ, Schostarez HJ, Mitchell MA: Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity. Protein Sci. 1998 Oct;7(10):2118-26. [PubMed:9792098]
  16. Chen L, Rydel TJ, Gu F, Dunaway CM, Pikul S, Dunham KM, Barnett BL: Crystal structure of the stromelysin catalytic domain at 2.0 A resolution: inhibitor-induced conformational changes. J Mol Biol. 1999 Oct 29;293(3):545-57. [PubMed:10543949]
  17. Pavlovsky AG, Williams MG, Ye QZ, Ortwine DF, Purchase CF 2nd, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D, Humblet C, Blundell TL: X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity. Protein Sci. 1999 Jul;8(7):1455-62. [PubMed:10422833]
  18. Li YC, Zhang X, Melton R, Ganu V, Gonnella NC: Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor. Biochemistry. 1998 Oct 6;37(40):14048-56. [PubMed:9760240]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01877N-Hydroxy 1n(4-Methoxyphenyl)Sulfonyl-4-(Z,E-N-Methoxyimino)Pyrrolidine-2r-CarboxamideexperimentalunknownDetails
DB019963-MethylpyridineexperimentalunknownDetails
DB02090A Disubstituted Succinyl Caprolactam Hydroxymate Mmp3inhibitorexperimentalunknownDetails
DB02350N-Hydroxy-4-[(4-Methoxylphenyl)Sulfonyl]-2,2-Dimethyl-Hexahydro-1,4-Thiazepine-3(S)-CarboxamideexperimentalunknownDetails
DB02367(1n)-4-N-Butoxyphenylsulfonyl-(2r)-N-Hydroxycarboxamido-(4s)-Methanesulfonylamino-PyrrolidineexperimentalunknownDetails
DB024493-(1h-Indol-3-Yl)-2-[4-(4-Phenyl-Piperidin-1-Yl)-Benzenesulfonylamino]-Propionic AcidexperimentalunknownDetails
DB02697HydroxyaminovalineexperimentalunknownDetails
DB030331-Methyloxy-4-Sulfone-BenzeneexperimentalunknownDetails
DB033685-Methyl-5-(4-Phenoxy-Phenyl)-Pyrimidine-2,4,6-TrioneexperimentalunknownDetails
DB041401-Benzyl-3-(4-Methoxy-Benzenesulfonyl)-6-Oxo-Hexahydro-Pyrimidine-4-Carboxylic Acid HydroxyamideexperimentalunknownDetails
DB04232N-Hydroxy-1-(4-Methoxyphenyl)Sulfonyl-4-Benzyloxycarbonyl-Piperazine-2-CarboxamideexperimentalunknownDetails
DB04416R-2-{[4'-Methoxy-(1,1'-Biphenyl)-4-Yl]-Sulfonyl}-Amino-6-Methoxy-Hex-4-Ynoic AcidexperimentalunknownDetails
DB00786MarimastatinvestigationalyesantagonistDetails
DB073902-[3-(5-MERCAPTO-[1,3,4]THIADIAZOL-2-YL)-UREIDO]-N-METHYL-3-PHENYL-PROPIONAMIDEexperimentalunknownDetails
DB07986[4-(4-PHENYL-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-ACETIC ACIDexperimentalunknownDetails
DB07987[2-(5-MERCAPTO-[1,3,4]THIADIAZOL-2-YLCARBAMOYL)-1-PHENYL-ETHYL]-CARBAMIC ACID BENZYL ESTERexperimentalunknownDetails
DB079882-[3-(5-MERCAPTO-[1,3,4]THIADIAZOL-2YL)-UREIDO]-N-METHYL-3-PENTAFLUOROPHENYL-PROPIONAMIDEexperimentalunknownDetails
DB08029N~2~-(biphenyl-4-ylsulfonyl)-N-hydroxy-N~2~-(2-hydroxyethyl)glycinamideexperimentalunknownDetails
DB080303-[(4'-cyanobiphenyl-4-yl)oxy]-N-hydroxypropanamideexperimentalunknownDetails
DB08271N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACIDexperimentalunknownDetails
DB08507N-[[2-METHYL-4-HYDROXYCARBAMOYL]BUT-4-YL-N]-BENZYL-P-[PHENYL]-P-[METHYL]PHOSPHINAMIDexperimentalunknownDetails
DB086432-(2-{2-[(BIPHENYL-4-YLMETHYL)-AMINO]-3-MERCAPTO-PENTANOYLAMINO}-ACETYLAMINO)-3-METHYL-BUTYRIC ACID METHYL ESTERexperimentalunknownDetails