ID MMP3_MOUSE Reviewed; 477 AA. AC P28862; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 2. DT 02-SEP-2026, entry version 203. DE RecName: Full=Stromelysin-1; DE Short=SL-1; DE EC=3.4.24.17; DE AltName: Full=EMS-2; DE AltName: Full=Matrix metalloproteinase-3; DE Short=MMP-3; DE AltName: Full=Transin-1; DE Flags: Precursor; GN Name=Mmp3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=NMRI; TISSUE=Calvaria; RX PubMed=1398148; DOI=10.1016/0378-1119(92)90116-7; RA Hammani K., Henriet P., Eeckhout Y.; RT "Cloning and sequencing of a cDNA encoding mouse stromelysin 1."; RL Gene 120:321-322(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=SWR/J; RA Li F., Strange R., Saurer S., Niemann H., Friis R.R.; RL Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 415-469, AND DEVELOPMENTAL STAGE. RX PubMed=2744464; DOI=10.1101/gad.3.6.848; RA Brenner C.A., Adler R.R., Rappolee D.A., Pedersen R.A., Werb Z.; RT "Genes for extracellular-matrix-degrading metalloproteinases and their RT inhibitor, TIMP, are expressed during early mammalian development."; RL Genes Dev. 3:848-859(1989). RN [4] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=17116747; DOI=10.1096/fj.06-5865com; RA Kim Y.S., Choi D.H., Block M.L., Lorenzl S., Yang L., Kim Y.J., Sugama S., RA Cho B.P., Hwang O., Browne S.E., Kim S.Y., Hong J.S., Beal M.F., Joh T.H.; RT "A pivotal role of matrix metalloproteinase-3 activity in dopaminergic RT neuronal degeneration via microglial activation."; RL FASEB J. 21:179-187(2007). RN [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=35940311; DOI=10.1016/j.antiviral.2022.105388; RA Feng T., Tong H., Ming Z., Deng L., Liu J., Wu J., Chen Z., Yan Y., Dai J.; RT "Matrix metalloproteinase 3 restricts viral infection by enhancing host RT antiviral immunity."; RL Antiviral Res. 0:0-0(2022). CC -!- FUNCTION: Metalloproteinase with a rather broad substrate specificity CC that can degrade fibronectin, laminin, gelatins of type I, III, IV, and CC V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates CC different molecules including growth factors, plasminogen or other CC matrix metalloproteinases such as MMP9. Once released into the CC extracellular matrix (ECM), the inactive pro-enzyme is activated by the CC plasmin cascade signaling pathway. Also acts intracellularly. For CC example, in dopaminergic neurons, gets activated by the serine protease CC HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration CC by mediating microglial activation and alpha-synuclein/SNCA cleavage CC (PubMed:17116747). In addition, plays a role in immune response and CC possesses antiviral activity against various viruses (PubMed:35940311). CC Mechanistically, translocates from the cytoplasm into the cell nucleus CC upon virus infection to influence NF-kappa-B activities CC (PubMed:35940311). {ECO:0000250|UniProtKB:P08254, CC ECO:0000269|PubMed:17116747, ECO:0000269|PubMed:35940311}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage where P1', P2' and P3' are hydrophobic CC residues.; EC=3.4.24.17; Evidence={ECO:0000250|UniProtKB:P08254}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000250}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250}; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000305}. CC -!- DEVELOPMENTAL STAGE: Present in unfertilized eggs and at the zygote and CC cleavage stages. Levels increase at the blastocyst stage and with CC endoderm differentiation. {ECO:0000269|PubMed:2744464}. 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 -!- DISRUPTION PHENOTYPE: MMP3-deficient mice have impaired antiviral CC cytokine and chemokine responses at early stage of viral infections CC (PubMed:35940311). In addition, neuronal degeneration, microglial CC activation, and superoxide generation are largely attenuated in these CC mutant mice (PubMed:17116747). {ECO:0000269|PubMed:17116747, CC ECO:0000269|PubMed:35940311}. CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA44860.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X66402; CAA47029.1; -; mRNA. DR EMBL; X63162; CAA44860.1; ALT_INIT; mRNA. DR CCDS; CCDS22806.1; -. DR PIR; JC1476; KCMSS1. DR RefSeq; NP_034939.2; NM_010809.3. DR AlphaFoldDB; P28862; -. DR SMR; P28862; -. DR FunCoup; P28862; 149. DR STRING; 10090.ENSMUSP00000034497; -. DR MEROPS; M10.005; -. DR MoonProt; P28862; -. DR iPTMnet; P28862; -. DR PhosphoSitePlus; P28862; -. DR CPTAC; non-CPTAC-3423; -. DR PaxDb; 10090-ENSMUSP00000034497; -. DR PeptideAtlas; P28862; -. DR ProteomicsDB; 295693; -. DR ABCD; P28862; 1 sequenced antibody. DR DNASU; 17392; -. DR Ensembl; ENSMUST00000034497.9; ENSMUSP00000034497.8; ENSMUSG00000043613.9. DR GeneID; 17392; -. DR KEGG; mmu:17392; -. DR AGR; MGI:97010; -. DR CTD; 4314; -. DR MGI; MGI:97010; Mmp3. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000159759; -. DR InParanoid; P28862; -. DR OrthoDB; 406838at2759; -. DR BRENDA; 3.4.24.17; 3474. DR Reactome; R-MMU-1442490; Collagen degradation. DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix. DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-MMU-2022090; Assembly of collagen fibrils and other multimeric structures. DR Reactome; R-MMU-2179392; EGFR Transactivation by Gastrin. DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling. DR BioGRID-ORCS; 17392; 2 hits in 79 CRISPR screens. DR PRO; PR:P28862; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P28862; protein. DR ExpressionAtlas; P28862; baseline and differential. DR GO; GO:0044297; C:cell body; ISO:GO_Central. DR GO; GO:0005737; C:cytoplasm; ISO:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL. DR GO; GO:0030425; C:dendrite; ISO:GO_Central. DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL. DR GO; GO:0005634; C:nucleus; ISO:GO_Central. DR GO; GO:0032991; C:protein-containing complex; ISO:GO_Central. DR GO; GO:0004175; F:endopeptidase activity; ISO:GO_Central. DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; ISO:GO_Central. DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:ParkinsonsUK-UCL. DR GO; GO:0071492; P:cellular response to UV-A; ISS:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ParkinsonsUK-UCL. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:GO_Central. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:GO_Central. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:GO_Central. DR GO; GO:0030163; P:protein catabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0006508; P:proteolysis; IMP:ParkinsonsUK-UCL. DR GO; GO:0030334; P:regulation of cell migration; IMP:MGI. DR CDD; cd00094; HX; 1. DR CDD; cd04278; ZnMc_MMP; 1. DR FunFam; 3.40.390.10:FF:000007; Collagenase 3; 1. DR FunFam; 2.110.10.10:FF:000002; Matrix metallopeptidase 3; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 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 PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1. DR PANTHER; PTHR10201:SF215; STROMELYSIN-1; 1. 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; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF47090; PGBD-like; 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 2: Evidence at transcript level; KW Calcium; Collagen degradation; Disulfide bond; Extracellular matrix; KW Hydrolase; Immunity; Innate immunity; Metal-binding; Metalloprotease; KW Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..17 FT /evidence="ECO:0000305" FT PROPEP 18..99 FT /note="Activation peptide" FT /id="PRO_0000028730" FT CHAIN 100..477 FT /note="Stromelysin-1" FT /id="PRO_0000028731" 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 MOTIF 90..97 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT ACT_SITE 219 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" 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 /evidence="ECO:0000250" FT BINDING 124 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 168 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 170 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 175 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 178 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 180 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 183 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 190 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 192 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 194 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 196 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 198 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 218 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 222 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 228 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" 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 CONFLICT 468 FT /note="I -> T (in Ref. 3)" FT /evidence="ECO:0000305" SQ SEQUENCE 477 AA; 53845 MW; 9C15594F45262D37 CRC64; MKGLPVLLWL CVVVCSSYPL HDSARDDDAG MELLQKYLEN YYGLAKDVKQ FIKKKDSSLI VKKIQEMQKF LGLEMTGKLD SNTMELMHKP RCGVPDVGGF STFPGSPKWR KSHITYRIVN YTPDLPRQSV DSAIEKALKV WEEVTPLTFS RISEGEADIM ISFAVGEHGD FVPFDGPGTV LAHAYAPGPG INGDAHFDDD ERWTEDVTGT NLFLVAAHEL GHSLGLYHSA KAEALMYPVY KSSTDLSRFH LSQDDVDGIQ SLYGTPTASP DVLVVPTKSN SLEPETSPMC SSTLFFDAVS TLRGEVLFFK DRHFWRKSLR TPEPEFYLIS SFWPSLPSNM DAAYEVTNRD TVFIFKGNQF WAIRGHEELA GYPKSIHTLG LPATVKKIDA AISNKEKRKT YFFVEDKYWR FDEKKQSMEP GFPRKIAEDF PGVDSRVDAV FEAFGFLYFF SGSSQLEFDP NAKKVTHILK SNSWFNC //