MMP12_HUMAN
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 03-AUG-2022, entry version 214.
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 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 AlphaFoldDB; P39900; -.
DR BMRB; P39900; -.
DR SASBDB; P39900; -.
DR SMR; P39900; -.
DR BioGRID; 110464; 3.
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 GlyGen; P39900; 2 sites.
DR iPTMnet; P39900; -.
DR PhosphoSitePlus; P39900; -.
DR BioMuta; MMP12; -.
DR DMDM; 729179; -.
DR jPOST; P39900; -.
DR MassIVE; P39900; -.
DR PeptideAtlas; P39900; -.
DR PRIDE; P39900; -.
DR ProteomicsDB; 55327; -.
DR TopDownProteomics; P39900; -.
DR ABCD; P39900; 7 sequenced antibodies.
DR Antibodypedia; 61960; 627 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 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; VDNQYWR; -.
DR OrthoDB; 1075463at2759; -.
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; 7 hits in 209 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 tissues.
DR Genevisible; P39900; HS.
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; 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 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
