ID MMP12_HUMAN Reviewed; 470 AA. AC P39900; B2R9X8; B7ZLF6; Q2M1L9; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 27-MAR-2024, entry version 223. DE RecName: Full=Macrophage metalloelastase; DE Short=MME; DE EC=3.4.24.65; DE AltName: Full=Macrophage elastase; DE Short=ME; DE Short=hME; DE AltName: Full=Matrix metalloproteinase-12; DE Short=MMP-12; DE Flags: Precursor; GN Name=MMP12; Synonyms=HME; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Alveolar macrophage; RX PubMed=8226919; DOI=10.1016/s0021-9258(20)80459-1; RA Shapiro S.D., Kobayashi D.K., Ley T.J.; RT "Cloning and characterization of a unique elastolytic metalloproteinase RT produced by human alveolar macrophages."; RL J. Biol. Chem. 268:23824-23829(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-357 AND ARG-469. RG NIEHS SNPs program; RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Esophagus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-357. 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). RN [6] RP CHARACTERIZATION. RX PubMed=9115292; DOI=10.1074/jbc.272.18.12189; RA Gronski T.J. Jr., Martin R.L., Kobayashi D.K., Walsh B.C., Holman M.C., RA Huber M., Van Wart H.E., Shapiro S.D.; RT "Hydrolysis of a broad spectrum of extracellular matrix proteins by human RT macrophage elastase."; RL J. Biol. Chem. 272:12189-12194(1997). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 106-263. RX PubMed=11575928; DOI=10.1006/jmbi.2001.4954; RA Lang R., Kocourek A., Braun M., Tschesche H., Huber R., Bode W., Maskos K.; RT "Substrate specificity determinants of human macrophage elastase (MMP-12) RT based on the 1.1 A crystal structure."; RL J. Mol. Biol. 312:731-742(2001). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 100-280. RX PubMed=11575929; DOI=10.1006/jmbi.2001.4953; RA Nar H., Werle K., Bauer M.M.T., Dollinger H., Jung B.; RT "Crystal structure of human macrophage elastase (MMP-12) in complex with a RT hydroxamic acid inhibitor."; RL J. Mol. Biol. 312:743-751(2001). 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. 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; CC Note=Binds 4 Ca(2+) ions per subunit.; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Note=Binds 2 Zn(2+) ions per subunit.; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Found in alveolar macrophages but not in peripheral CC blood monocytes. CC -!- INDUCTION: By exposure to bacterial lipopolysaccharides (LPS). CC Inhibited by dexamethasone. 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 -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mmp12/"; 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; L23808; AAA58658.1; ALT_SEQ; mRNA. DR EMBL; AY856072; AAW29944.1; -; Genomic_DNA. DR EMBL; AK313959; BAG36675.1; -; mRNA. DR EMBL; CH471065; EAW67033.1; -; Genomic_DNA. DR EMBL; BC112301; AAI12302.1; -; mRNA. DR EMBL; BC143773; AAI43774.1; -; mRNA. DR CCDS; CCDS73375.1; -. DR PIR; A49499; A49499. DR RefSeq; NP_002417.2; NM_002426.5. DR PDB; 1JIZ; X-ray; 2.60 A; A/B=100-264. DR PDB; 1JK3; X-ray; 1.09 A; A=106-263. DR PDB; 1OS2; X-ray; 2.15 A; A/B/C/D/E/F=106-268. DR PDB; 1OS9; X-ray; 1.85 A; A/B/C/D/E/F=106-268. DR PDB; 1RMZ; X-ray; 1.34 A; A=106-263. DR PDB; 1ROS; X-ray; 2.00 A; A/B=106-268. DR PDB; 1UTT; X-ray; 2.20 A; A=106-264. DR PDB; 1UTZ; X-ray; 2.50 A; A/B=106-264. DR PDB; 1Y93; X-ray; 1.03 A; A=106-263. DR PDB; 1YCM; NMR; -; A=106-263. DR PDB; 1Z3J; NMR; -; A=106-263. DR PDB; 2HU6; X-ray; 1.32 A; A=106-263. DR PDB; 2JXY; NMR; -; A=278-470. DR PDB; 2K2G; NMR; -; A=100-263. DR PDB; 2K9C; NMR; -; A=112-263. DR PDB; 2KRJ; NMR; -; A=112-263. DR PDB; 2MLR; NMR; -; A=100-263. DR PDB; 2MLS; NMR; -; A=100-263. DR PDB; 2N8R; NMR; -; A=100-263. DR PDB; 2OXU; X-ray; 1.24 A; A=106-263. DR PDB; 2OXW; X-ray; 1.15 A; A=106-263. DR PDB; 2OXZ; X-ray; 1.90 A; A=106-263. DR PDB; 2POJ; NMR; -; A=100-263. DR PDB; 2W0D; X-ray; 2.00 A; A/B/C/D=106-263. DR PDB; 2WO8; X-ray; 2.00 A; A/B/C/D=106-268. DR PDB; 2WO9; X-ray; 1.70 A; A/B/C/D=106-268. DR PDB; 2WOA; X-ray; 2.30 A; A/B/C/D=106-268. DR PDB; 2Z2D; NMR; -; A=100-263. DR PDB; 3BA0; X-ray; 3.00 A; A=106-470. DR PDB; 3EHX; X-ray; 1.90 A; A=106-263. DR PDB; 3EHY; X-ray; 1.90 A; A=106-263. DR PDB; 3F15; X-ray; 1.70 A; A=106-263. DR PDB; 3F16; X-ray; 1.16 A; A=106-263. DR PDB; 3F17; X-ray; 1.10 A; A=106-263. DR PDB; 3F18; X-ray; 1.13 A; A=106-263. DR PDB; 3F19; X-ray; 1.13 A; A=106-263. DR PDB; 3F1A; X-ray; 1.25 A; A=106-263. DR PDB; 3LIK; X-ray; 1.80 A; A=106-263. DR PDB; 3LIL; X-ray; 1.80 A; A=106-263. DR PDB; 3LIR; X-ray; 1.90 A; A=106-263. DR PDB; 3LJG; X-ray; 1.31 A; A=106-263. DR PDB; 3LK8; X-ray; 1.80 A; A=106-263. DR PDB; 3LKA; X-ray; 1.80 A; A=106-263. DR PDB; 3N2U; X-ray; 1.81 A; A=106-263. DR PDB; 3N2V; X-ray; 1.55 A; A=106-263. DR PDB; 3NX7; X-ray; 1.80 A; A=106-263. DR PDB; 3RTS; X-ray; 1.81 A; A=106-263. DR PDB; 3RTT; X-ray; 1.82 A; A=106-263. DR PDB; 3TS4; X-ray; 1.59 A; A=106-263. DR PDB; 3TSK; X-ray; 2.00 A; A=106-263. DR PDB; 3UVC; X-ray; 1.30 A; A/B=106-263. DR PDB; 4EFS; X-ray; 1.63 A; A=106-263. DR PDB; 4GQL; X-ray; 1.15 A; A=106-263. DR PDB; 4GR0; X-ray; 1.50 A; A=106-263. DR PDB; 4GR3; X-ray; 1.49 A; A=106-263. DR PDB; 4GR8; X-ray; 1.30 A; A=111-262. DR PDB; 4GUY; X-ray; 2.00 A; A=106-263. DR PDB; 4H30; X-ray; 1.43 A; A/B=106-263. DR PDB; 4H49; X-ray; 2.16 A; A/B/C/D=106-263. DR PDB; 4H76; X-ray; 1.50 A; A=106-263. DR PDB; 4H84; X-ray; 1.59 A; A/B=106-263. DR PDB; 4I03; X-ray; 1.70 A; A=106-263. DR PDB; 4IJO; X-ray; 1.90 A; A=106-263. DR PDB; 5CXA; X-ray; 1.30 A; A=106-263. DR PDB; 5CZM; X-ray; 1.30 A; A=106-263. DR PDB; 5D2B; X-ray; 1.20 A; A=106-263. DR PDB; 5D3C; X-ray; 1.31 A; A=106-263. DR PDB; 5I0L; X-ray; 2.45 A; A/B=106-263. DR PDB; 5I2Z; X-ray; 2.30 A; A/B/C/D=106-263. DR PDB; 5I3M; X-ray; 2.17 A; A/B/C/D=106-263. DR PDB; 5I43; X-ray; 1.95 A; A/B/C/D=106-263. DR PDB; 5I4O; X-ray; 2.05 A; A/B/C/D=106-263. DR PDB; 5L79; X-ray; 2.07 A; A=106-263. DR PDB; 5L7F; X-ray; 1.80 A; A/B=106-263. DR PDB; 5LAB; X-ray; 1.34 A; A=106-263. DR PDB; 5N5J; X-ray; 1.80 A; A=106-263. DR PDB; 5N5K; X-ray; 1.80 A; A=108-263. DR PDB; 6EKN; X-ray; 1.20 A; A=106-263. DR PDB; 6ELA; X-ray; 1.49 A; A/B/C/D=106-263. DR PDB; 6ENM; X-ray; 1.59 A; A/B=106-263. DR PDB; 6EOX; X-ray; 1.30 A; A=106-263. DR PDB; 6RD0; X-ray; 1.90 A; A=106-263. DR PDB; 6RLY; X-ray; 2.20 A; A=106-263. DR PDB; 7OVY; X-ray; 1.24 A; A=106-263. DR PDB; 8B2N; X-ray; 1.85 A; A/C=106-263. DR PDBsum; 1JIZ; -. DR PDBsum; 1JK3; -. DR PDBsum; 1OS2; -. DR PDBsum; 1OS9; -. DR PDBsum; 1RMZ; -. DR PDBsum; 1ROS; -. DR PDBsum; 1UTT; -. DR PDBsum; 1UTZ; -. DR PDBsum; 1Y93; -. DR PDBsum; 1YCM; -. DR PDBsum; 1Z3J; -. DR PDBsum; 2HU6; -. DR PDBsum; 2JXY; -. DR PDBsum; 2K2G; -. DR PDBsum; 2K9C; -. DR PDBsum; 2KRJ; -. DR PDBsum; 2MLR; -. DR PDBsum; 2MLS; -. DR PDBsum; 2N8R; -. DR PDBsum; 2OXU; -. DR PDBsum; 2OXW; -. DR PDBsum; 2OXZ; -. DR PDBsum; 2POJ; -. DR PDBsum; 2W0D; -. DR PDBsum; 2WO8; -. DR PDBsum; 2WO9; -. DR PDBsum; 2WOA; -. DR PDBsum; 2Z2D; -. DR PDBsum; 3BA0; -. DR PDBsum; 3EHX; -. DR PDBsum; 3EHY; -. DR PDBsum; 3F15; -. DR PDBsum; 3F16; -. DR PDBsum; 3F17; -. DR PDBsum; 3F18; -. DR PDBsum; 3F19; -. DR PDBsum; 3F1A; -. DR PDBsum; 3LIK; -. DR PDBsum; 3LIL; -. DR PDBsum; 3LIR; -. DR PDBsum; 3LJG; -. DR PDBsum; 3LK8; -. DR PDBsum; 3LKA; -. DR PDBsum; 3N2U; -. DR PDBsum; 3N2V; -. DR PDBsum; 3NX7; -. DR PDBsum; 3RTS; -. DR PDBsum; 3RTT; -. DR PDBsum; 3TS4; -. DR PDBsum; 3TSK; -. DR PDBsum; 3UVC; -. DR PDBsum; 4EFS; -. DR PDBsum; 4GQL; -. DR PDBsum; 4GR0; -. DR PDBsum; 4GR3; -. DR PDBsum; 4GR8; -. DR PDBsum; 4GUY; -. DR PDBsum; 4H30; -. DR PDBsum; 4H49; -. DR PDBsum; 4H76; -. DR PDBsum; 4H84; -. DR PDBsum; 4I03; -. DR PDBsum; 4IJO; -. DR PDBsum; 5CXA; -. DR PDBsum; 5CZM; -. DR PDBsum; 5D2B; -. DR PDBsum; 5D3C; -. DR PDBsum; 5I0L; -. DR PDBsum; 5I2Z; -. DR PDBsum; 5I3M; -. DR PDBsum; 5I43; -. DR PDBsum; 5I4O; -. DR PDBsum; 5L79; -. DR PDBsum; 5L7F; -. DR PDBsum; 5LAB; -. DR PDBsum; 5N5J; -. DR PDBsum; 5N5K; -. DR PDBsum; 6EKN; -. DR PDBsum; 6ELA; -. DR PDBsum; 6ENM; -. DR PDBsum; 6EOX; -. DR PDBsum; 6RD0; -. DR PDBsum; 6RLY; -. DR PDBsum; 7OVY; -. DR PDBsum; 8B2N; -. DR AlphaFoldDB; P39900; -. DR BMRB; P39900; -. DR SASBDB; P39900; -. DR SMR; P39900; -. DR BioGRID; 110464; 5. DR IntAct; P39900; 2. DR MINT; P39900; -. DR STRING; 9606.ENSP00000458585; -. DR BindingDB; P39900; -. DR ChEMBL; CHEMBL4393; -. DR DrugBank; DB07026; (1S,5S,7R)-N~7~-(BIPHENYL-4-YLMETHYL)-N~3~-HYDROXY-6,8-DIOXA-3-AZABICYCLO[3.2.1]OCTANE-3,7-DICARBOXAMIDE. DR DrugBank; DB07921; 2-[(4-fluorophenyl)sulfonylamino]-N-oxo-ethanamide. DR DrugBank; DB04405; 2-[2-(1,3-Dioxo-1,3-Dihydro-2h-Isoindol-2-Yl)Ethyl]-4-(4'-Ethoxy-1,1'-Biphenyl-4-Yl)-4-Oxobutanoic Acid. DR DrugBank; DB00551; Acetohydroxamic acid. DR DrugBank; DB05387; AE-941. DR DrugBank; DB03880; Batimastat. DR DrugBank; DB07556; CGS-27023. DR DrugBank; DB02118; CP-271485. DR DrugBank; DB00786; Marimastat. DR DrugBank; DB07446; N-(biphenyl-4-ylsulfonyl)-D-leucine. DR DrugBank; DB07683; N-(dibenzo[b,d]thiophen-3-ylsulfonyl)-L-valine. DR DrugBank; DB08599; N-[(4-methoxyphenyl)sulfonyl]-D-alanine. DR DrugBank; DB08271; N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID. DR DrugBank; DB07922; N-oxo-2-(phenylsulfonylamino)ethanamide. DR DrugBank; DB07920; N-oxo-2-[(4-phenylphenyl)sulfonylamino]ethanamide. DR DrugBank; DB03367; PF-00356231. DR DrugBank; DB00013; Urokinase. DR DrugCentral; P39900; -. DR GuidetoPHARMACOLOGY; 1636; -. DR MEROPS; M10.009; -. DR GlyCosmos; P39900; 2 sites, No reported glycans. DR GlyGen; P39900; 2 sites. DR iPTMnet; P39900; -. DR PhosphoSitePlus; P39900; -. DR BioMuta; MMP12; -. DR DMDM; 729179; -. DR jPOST; P39900; -. DR MassIVE; P39900; -. DR PaxDb; 9606-ENSP00000458585; -. DR PeptideAtlas; P39900; -. DR ProteomicsDB; 55327; -. DR TopDownProteomics; P39900; -. DR ABCD; P39900; 7 sequenced antibodies. DR Antibodypedia; 61960; 715 antibodies from 41 providers. DR DNASU; 4321; -. DR Ensembl; ENST00000571244.3; ENSP00000458585.1; ENSG00000262406.3. DR GeneID; 4321; -. DR KEGG; hsa:4321; -. DR MANE-Select; ENST00000571244.3; ENSP00000458585.1; NM_002426.6; NP_002417.2. DR UCSC; uc031yde.2; human. DR AGR; HGNC:7158; -. DR CTD; 4321; -. DR DisGeNET; 4321; -. DR GeneCards; MMP12; -. DR HGNC; HGNC:7158; MMP12. DR HPA; ENSG00000262406; Tissue enhanced (intestine, lymphoid tissue, urinary bladder). DR MIM; 601046; gene. DR neXtProt; NX_P39900; -. DR OpenTargets; ENSG00000262406; -. DR PharmGKB; PA30870; -. DR VEuPathDB; HostDB:ENSG00000262406; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000162085; -. DR HOGENOM; CLU_015489_6_0_1; -. DR InParanoid; P39900; -. DR OMA; NYPKSIH; -. DR OrthoDB; 391167at2759; -. DR PhylomeDB; P39900; -. DR BRENDA; 3.4.24.65; 2681. DR PathwayCommons; P39900; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR SignaLink; P39900; -. DR SIGNOR; P39900; -. DR BioGRID-ORCS; 4321; 8 hits in 271 CRISPR screens. DR ChiTaRS; MMP12; human. DR EvolutionaryTrace; P39900; -. DR GeneWiki; Matrix_metallopeptidase_12; -. DR GenomeRNAi; 4321; -. DR Pharos; P39900; Tchem. DR PRO; PR:P39900; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P39900; Protein. DR Bgee; ENSG00000262406; Expressed in periodontal ligament and 92 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IMP:CAFA. DR GO; GO:0005634; C:nucleus; IMP:CAFA. DR GO; GO:0005509; F:calcium ion binding; IMP:CAFA. DR GO; GO:0005518; F:collagen binding; IPI:CAFA. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IMP:CAFA. DR GO; GO:0004175; F:endopeptidase activity; TAS:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:CAFA. DR GO; GO:0043565; F:sequence-specific DNA binding; IMP:CAFA. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; IMP:CAFA. DR GO; GO:0060435; P:bronchiole development; IEA:Ensembl. DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl. DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central. DR GO; GO:0060309; P:elastin catabolic process; IDA:ARUK-UCL. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:1904905; P:negative regulation of endothelial cell-matrix adhesion via fibronectin; IDA:ARUK-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0060054; P:positive regulation of epithelial cell proliferation involved in wound healing; IDA:BHF-UCL. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:CAFA. DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0006606; P:protein import into nucleus; IMP:CAFA. DR GO; GO:0006508; P:proteolysis; IDA:CAFA. DR GO; GO:0050691; P:regulation of defense response to virus by host; IEA:Ensembl. DR GO; GO:1904645; P:response to amyloid-beta; TAS:ARUK-UCL. DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; IDA:BHF-UCL. 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; 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: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; PS00546; CYSTEINE_SWITCH; 1. DR PROSITE; PS00024; HEMOPEXIN; 1. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P39900; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Disulfide bond; Extracellular matrix; Glycoprotein; KW Hydrolase; Metal-binding; Metalloprotease; Protease; Reference proteome; KW Repeat; Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000305" FT PROPEP 17..105 FT /note="Activation peptide" FT /evidence="ECO:0000250" FT /id="PRO_0000028776" FT CHAIN 106..470 FT /note="Macrophage metalloelastase" FT /id="PRO_0000028777" FT REPEAT 279..328 FT /note="Hemopexin 1" FT REPEAT 329..375 FT /note="Hemopexin 2" FT REPEAT 377..425 FT /note="Hemopexin 3" FT REPEAT 426..470 FT /note="Hemopexin 4" FT MOTIF 90..97 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT ACT_SITE 219 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 BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 168 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 170 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 175 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 178 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 180 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 183 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 190 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 192 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 194 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 196 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 198 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 218 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 222 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 228 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 289 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 333 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 381 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 430 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT CARBOHYD 20 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 285 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 282..470 FT /evidence="ECO:0000250" FT VARIANT 357 FT /note="N -> S (in dbSNP:rs652438)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2" FT /id="VAR_021343" FT VARIANT 469 FT /note="G -> R (in dbSNP:rs28381701)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_021344" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:2K2G" FT STRAND 110..118 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:2W0D" FT HELIX 127..142 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:4H84" FT STRAND 148..151 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 158..164 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 176..179 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:1JK3" FT TURN 190..193 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 203..211 FT /evidence="ECO:0007829|PDB:1Y93" FT HELIX 212..223 FT /evidence="ECO:0007829|PDB:1Y93" FT TURN 232..236 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:1Y93" FT HELIX 245..247 FT /evidence="ECO:0007829|PDB:1Y93" FT HELIX 252..259 FT /evidence="ECO:0007829|PDB:1Y93" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 266..268 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 281..284 FT /evidence="ECO:0007829|PDB:2JXY" FT STRAND 291..294 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 297..302 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 305..308 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 318..320 FT /evidence="ECO:0007829|PDB:3BA0" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 334..338 FT /evidence="ECO:0007829|PDB:3BA0" FT HELIX 339..341 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 343..348 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 351..354 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 357..360 FT /evidence="ECO:0007829|PDB:2JXY" FT TURN 361..363 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 365..367 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 368..372 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 382..386 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 387..390 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 391..396 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 399..404 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 405..408 FT /evidence="ECO:0007829|PDB:3BA0" FT HELIX 418..421 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 430..435 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 436..438 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 439..444 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 447..452 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 453..456 FT /evidence="ECO:0007829|PDB:3BA0" FT STRAND 457..463 FT /evidence="ECO:0007829|PDB:3BA0" FT TURN 464..469 FT /evidence="ECO:0007829|PDB:3BA0" SQ SEQUENCE 470 AA; 54002 MW; 8C745EEA8C0EA216 CRC64; MKFLLILLLQ ATASGALPLN SSTSLEKNNV LFGERYLEKF YGLEINKLPV TKMKYSGNLM KEKIQEMQHF LGLKVTGQLD TSTLEMMHAP RCGVPDVHHF REMPGGPVWR KHYITYRINN YTPDMNREDV DYAIRKAFQV WSNVTPLKFS KINTGMADIL VVFARGAHGD FHAFDGKGGI LAHAFGPGSG IGGDAHFDED EFWTTHSGGT NLFLTAVHEI GHSLGLGHSS DPKAVMFPTY KYVDINTFRL SADDIRGIQS LYGDPKENQR LPNPDNSEPA LCDPNLSFDA VTTVGNKIFF FKDRFFWLKV SERPKTSVNL ISSLWPTLPS GIEAAYEIEA RNQVFLFKDD KYWLISNLRP EPNYPKSIHS FGFPNFVKKI DAAVFNPRFY RTYFFVDNQY WRYDERRQMM DPGYPKLITK NFQGIGPKID AVFYSKNKYY YFFQGSNQFE YDFLLQRITK TLKSNSWFGC //