MMP12_RAT
ID MMP12_RAT Reviewed; 465 AA.
AC Q63341; Q5I0P0;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Macrophage metalloelastase;
DE Short=MME;
DE EC=3.4.24.65;
DE AltName: Full=Matrix metalloproteinase-12;
DE Short=MMP-12;
DE Flags: Precursor;
GN Name=Mmp12; Synonyms=Mmel;
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].
RC STRAIN=Sprague-Dawley;
RA Cossins J., Clements J., Catlin G.;
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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).
CC -!- FUNCTION: May be involved in tissue injury and remodeling. Has
CC significant elastolytic activity. Can accept large and small amino
CC acids at the P1' site, but has a preference for leucine. Aromatic or
CC hydrophobic residues are preferred at the P1 site, with small
CC hydrophobic residues (preferably alanine) occupying P3 (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of soluble and insoluble elastin. Specific
CC cleavages are also produced at 14-Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in
CC the B chain of insulin.; EC=3.4.24.65;
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:0000250}.
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 -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; X98517; CAA67142.1; -; mRNA.
DR EMBL; BC088120; AAH88120.1; -; mRNA.
DR RefSeq; NP_446415.2; NM_053963.2.
DR AlphaFoldDB; Q63341; -.
DR SMR; Q63341; -.
DR STRING; 10116.ENSRNOP00000011727; -.
DR BindingDB; Q63341; -.
DR ChEMBL; CHEMBL5506; -.
DR MEROPS; M10.009; -.
DR GlyGen; Q63341; 1 site.
DR PaxDb; Q63341; -.
DR PRIDE; Q63341; -.
DR GeneID; 117033; -.
DR KEGG; rno:117033; -.
DR UCSC; RGD:620195; rat.
DR CTD; 4321; -.
DR RGD; 620195; Mmp12.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; Q63341; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q63341; -.
DR TreeFam; TF315428; -.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR PRO; PR:Q63341; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0060435; P:bronchiole development; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0060309; P:elastin catabolic process; ISO:RGD.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:1904905; P:negative regulation of endothelial cell-matrix adhesion via fibronectin; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISO:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEP:RGD.
DR GO; GO:0060054; P:positive regulation of epithelial cell proliferation involved in wound healing; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0050691; P:regulation of defense response to virus by host; ISO:RGD.
DR GO; GO:1901163; P:regulation of trophoblast cell migration; IMP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; ISO: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; 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; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Calcium; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000305"
FT PROPEP 22..101
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028782"
FT CHAIN 102..465
FT /note="Macrophage metalloelastase"
FT /id="PRO_0000028783"
FT REPEAT 281..324
FT /note="Hemopexin 1"
FT REPEAT 325..371
FT /note="Hemopexin 2"
FT REPEAT 373..421
FT /note="Hemopexin 3"
FT REPEAT 422..465
FT /note="Hemopexin 4"
FT MOTIF 86..93
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 88
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 120
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 174
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 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
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 224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 278..465
FT /evidence="ECO:0000250"
FT CONFLICT 223
FT /note="R -> P (in Ref. 2; AAH88120)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="D -> H (in Ref. 2; AAH88120)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 465 AA; 53738 MW; E779B6014EC6FF68 CRC64;
MKFLLVLVLL VSLQVSACGA APMNESEFAE WYLSRFFDYQ GDRIPMTKTK TNRNLLEEKL
QEMQQFFGLE VTGQLDTSTL KIMHTSRCGV PDVQHLRAVP QRSRWMKRYL TYRIYNYTPD
MKRADVDYIF QKAFQVWSDV TPLRFRKIHK GEADITILFA FGDHGDFYDF DGKGGTLAHA
FYPGPGIQGD AHFDEAETWT KSFQGTNLFL VAVHELGHSL GLRHSNNPKS IMYPTYRYLH
PNTFRLSADD IHSIQSLYGA PVKNPSLTNP GSPPSTVCHQ SLSFDAVTTV GDKIFFFKDW
FFWWRLPGSP ATNITSISSM WPTIPSGIQA AYEIGGRNQL FLFKDEKYWL INNLVPEPHY
PRSIHSLGFP ASVKKIDAAV FDPLRQKVYF FVDKQYWRYD VRQELMDAAY PKLISTHFPG
IRPKIDAVLY FKRHYYIFQG AYQLEYDPLL DRVTKTLSST SWFGC
