MMP3_RAT
ID MMP3_RAT Reviewed; 475 AA.
AC P03957;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-1986, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Stromelysin-1;
DE Short=SL-1;
DE EC=3.4.24.17 {ECO:0000269|PubMed:1963430, ECO:0000269|PubMed:1988438, ECO:0000269|PubMed:2841336};
DE AltName: Full=Matrix metalloproteinase-3;
DE Short=MMP-3;
DE AltName: Full=PTR1 protein;
DE AltName: Full=Transin-1;
DE Flags: Precursor;
GN Name=Mmp3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3875482; DOI=10.1002/j.1460-2075.1985.tb03799.x;
RA Matrisian L.M., Glaichenhaus N., Gesnel M.-C., Breathnach R.;
RT "Epidermal growth factor and oncogenes induce transcription of the same
RT cellular mRNA in rat fibroblasts.";
RL EMBO J. 4:1435-1440(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2431284; DOI=10.1128/mcb.6.5.1679-1686.1986;
RA Matrisian L.M., Gleroy P., Ruhlmann C., Gesnel M.-C., Breathnach R.;
RT "Isolation of the oncogene and epidermal growth factor-induced transin
RT gene: complex control in rat fibroblasts.";
RL Mol. Cell. Biol. 6:1679-1686(1986).
RN [3]
RP PROTEIN SEQUENCE OF 19-28; 110-119; 309-315 AND 316-325, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=1963430; DOI=10.1093/oxfordjournals.jbchem.a123238;
RA Umenishi F., Yasumitsu H., Ashida Y., Yamauti J., Umeda M., Miyazaki K.;
RT "Purification and properties of extracellular matrix-degrading metallo-
RT proteinase overproduced by Rous sarcoma virus-transformed rat liver cell
RT line, and its identification as transin.";
RL J. Biochem. 108:537-543(1990).
RN [4]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DOMAIN,
RP PROTEOLYTIC CLEAVAGE, ACTIVE SITE, AND MUTAGENESIS OF PRO-88; PRO-93;
RP PHE-98; HIS-216; GLU-217 AND HIS-226.
RX PubMed=2841336; DOI=10.1016/s0021-9258(18)37870-0;
RA Sanchez-Lopez R., Nicholson R., Gesnel M.-C., Matrisian L.M.,
RA Breathnach R.;
RT "Structure-function relationships in the collagenase family member
RT transin.";
RL J. Biol. Chem. 263:11892-11899(1988).
RN [5]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DOMAIN,
RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF MET-85; PRO-88; ARG-89; CYS-90;
RP GLY-91; VAL-92 AND PRO-93.
RX PubMed=1988438; DOI=10.1016/s0021-9258(18)52334-6;
RA Park A.J., Matrisian L.M., Kells A.F., Pearson R., Yuan Z.Y., Navre M.;
RT "Mutational analysis of the transin (rat stromelysin) autoinhibitor region
RT demonstrates a role for residues surrounding the cysteine switch.";
RL J. Biol. Chem. 266:1584-1590(1991).
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. {ECO:0000269|PubMed:1963430}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage where P1', P2' and P3' are hydrophobic
CC residues.; EC=3.4.24.17; Evidence={ECO:0000269|PubMed:1963430,
CC ECO:0000269|PubMed:1988438, ECO:0000269|PubMed:2841336};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:1963430};
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 -!- ACTIVITY REGULATION: Inhibited by a synthetic peptide corresponding to
CC the inhibitory cysteine switch motif (PubMed:1988438). Inhibited by
CC ethylenediaminetetraacetic acid (EDTA), 1,10-pheanthroline, 2-
CC mecaptoethanol, dithiothreitol and metalloproteinase inhibitor protein
CC TIMP (PubMed:1963430, PubMed:2841336). {ECO:0000269|PubMed:1963430,
CC ECO:0000269|PubMed:1988438, ECO:0000269|PubMed:2841336}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305}. Secreted {ECO:0000269|PubMed:1963430,
CC ECO:0000269|PubMed:1988438, ECO:0000269|PubMed:2841336}.
CC -!- INDUCTION: By epidermal growth factor and is increased in FR3T3 and
CC RAT-1 fibroblasts transformed by polyoma virus, Rous sarcoma virus, or
CC the human cellular H-Ras oncogene.
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. {ECO:0000269|PubMed:1988438,
CC ECO:0000269|PubMed:2841336}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; X02601; CAA26448.1; -; mRNA.
DR PIR; A00997; KCRTIH.
DR AlphaFoldDB; P03957; -.
DR SMR; P03957; -.
DR MEROPS; M10.005; -.
DR GlyGen; P03957; 1 site.
DR PhosphoSitePlus; P03957; -.
DR ABCD; P03957; 1 sequenced antibody.
DR UCSC; RGD:621317; rat.
DR RGD; 621317; Mmp3.
DR InParanoid; P03957; -.
DR PhylomeDB; P03957; -.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-RNO-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR PRO; PR:P03957; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:0071460; P:cellular response to cell-matrix adhesion; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
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:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0010727; P:negative regulation of hydrogen peroxide metabolic process; ISO:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:1903209; P:positive regulation of oxidative stress-induced cell death; ISO:RGD.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
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 Calcium; Collagen degradation; Direct protein sequencing; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000305"
FT PROPEP 18..97
FT /note="Activation peptide"
FT /evidence="ECO:0000303|PubMed:2841336"
FT /id="PRO_0000028734"
FT CHAIN 98..475
FT /note="Stromelysin-1"
FT /id="PRO_0000028735"
FT REPEAT 285..334
FT /note="Hemopexin 1"
FT REPEAT 335..381
FT /note="Hemopexin 2"
FT REPEAT 383..431
FT /note="Hemopexin 3"
FT REPEAT 432..475
FT /note="Hemopexin 4"
FT MOTIF 88..95
FT /note="Cysteine switch"
FT /evidence="ECO:0000269|PubMed:1988438,
FT ECO:0000269|PubMed:2841336"
FT ACT_SITE 217
FT /evidence="ECO:0000269|PubMed:2841336"
FT BINDING 90
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|UniProtKB:P03956"
FT BINDING 122
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 156
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 196
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 436
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 288..475
FT /evidence="ECO:0000250"
FT MUTAGEN 85
FT /note="M->L: Does not induce autoproteolytic activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 88
FT /note="P->A: Does not induce autoproteolytic activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 88
FT /note="P->G,L: Induces partial autoproteolytic activation."
FT /evidence="ECO:0000269|PubMed:1988438,
FT ECO:0000269|PubMed:2841336"
FT MUTAGEN 89
FT /note="R->K,L,Q: Induces constitutive autoproteolytic
FT activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 90
FT /note="C->S,H,D: Induces constitutive autoproteolytic
FT activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 91
FT /note="G->A: Induces constitutive autoproteolytic
FT activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 92
FT /note="V->G: Induces constitutive autoproteolytic
FT activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 92
FT /note="V->I,A: Induces partial autoproteolytic activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 92
FT /note="V->L,D: Does not induce autoproteolytic activation."
FT /evidence="ECO:0000269|PubMed:1988438"
FT MUTAGEN 93
FT /note="P->V,G,N: Induces partial autoproteolytic
FT activation."
FT /evidence="ECO:0000269|PubMed:1988438,
FT ECO:0000269|PubMed:2841336"
FT MUTAGEN 98
FT /note="F->S: Loss of autocleavage without affecting
FT activation by APMA."
FT /evidence="ECO:0000269|PubMed:2841336"
FT MUTAGEN 216
FT /note="H->L: Loss of autoproteolytic activation and
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:2841336"
FT MUTAGEN 217
FT /note="E->G: Loss of autoproteolytic activation and
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:2841336"
FT MUTAGEN 226
FT /note="H->S: Loss of autoproteolytic activation and
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:2841336"
SQ SEQUENCE 475 AA; 53428 MW; D81239DC3E26782E CRC64;
MKGLPVLLWL CTAVCSSYPL HGSEEDAGME VLQKYLENYY GLEKDVKQFT KKKDSSPVVK
KIQEMQKFLG LKMTGKLDSN TMELMHKPRC GVPDVGGFST FPGSPKWRKN HISYRIVNYT
LDLPRESVDS AIERALKVWE EVTPLTFSRI SEGEADIMIS FAVEEHGDFI PFDGPGMVLA
HAYAPGPGTN GDAHFDDDER WTDDVTGTNL FLVAAHELGH SLGLFHSANA EALMYPVYKS
STDLARFHLS QDDVDGIQSL YGPPTESPDV LVVPTKSNSL DPETLPMCSS ALSFDAVSTL
RGEVLFFKDR HFWRKSLRTP EPGFYLISSF WPSLPSNMDA AYEVTNRDTV FILKGNQIWA
IRGHEELAGY PKSIHTLGLP ETVQKIDAAI SLKDQKKTYF FVEDKFWRFD EKKQSMDPEF
PRKIAENFPG IGTKVDAVFE AFGFLYFFSG SSQLEFDPNA GKVTHILKSN SWFNC
