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 24-JAN-2024, entry version 169. 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}. 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; 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 GlyCosmos; Q63341; 1 site, No reported glycans. DR GlyGen; Q63341; 1 site. DR PhosphoSitePlus; Q63341; -. DR PaxDb; 10116-ENSRNOP00000011727; -. DR GeneID; 117033; -. DR KEGG; rno:117033; -. DR UCSC; RGD:620195; rat. DR AGR; RGD:620195; -. DR CTD; 4321; -. DR RGD; 620195; Mmp12. DR eggNOG; KOG1565; Eukaryota. DR InParanoid; Q63341; -. DR OrthoDB; 391167at2759; -. 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; 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; IPR006026; Peptidase_Metallo. DR InterPro; IPR002477; Peptidoglycan-bd-like. DR InterPro; IPR036365; PGBD-like_sf. DR PANTHER; PTHR10201:SF267; MACROPHAGE METALLOELASTASE; 1. DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 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; 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 //