ID MMP11_HUMAN Reviewed; 488 AA. AC P24347; Q5FX24; Q6PEZ6; Q9UC26; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 27-MAR-2024, entry version 214. DE RecName: Full=Stromelysin-3; DE Short=SL-3; DE Short=ST3; DE EC=3.4.24.-; DE AltName: Full=Matrix metalloproteinase-11; DE Short=MMP-11; DE Flags: Precursor; GN Name=MMP11; Synonyms=STMY3; 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], AND VARIANT VAL-38. RX PubMed=1701851; DOI=10.1038/348699a0; RA Basset P., Bellocq J.-P., Wolf C., Stoll I., Hutin P., Limacher J.-M., RA Podhajcer O.L., Chenard M.P., Rio M.C., Chambon P.; RT "A novel metalloproteinase gene specifically expressed in stromal cells of RT breast carcinomas."; RL Nature 348:699-704(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-38; LYS-44; LEU-61 AND RP PRO-86. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-182. RC TISSUE=Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36. RX PubMed=7657606; DOI=10.1074/jbc.270.35.20337; RA Anglard P., Melot T., Guerin E., Thomas G., Basset P.; RT "Structure and promoter characterization of the human stromelysin-3 gene."; RL J. Biol. Chem. 270:20337-20344(1995). RN [6] RP PROTEIN SEQUENCE OF 81-101. RX PubMed=7746327; DOI=10.1038/375244a0; RA Pei D., Weiss S.J.; RT "Furin-dependent intracellular activation of the human stromelysin-3 RT zymogen."; RL Nature 375:244-247(1995). RN [7] RP VARIANT [LARGE SCALE ANALYSIS] ASN-166. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: May play an important role in the progression of epithelial CC malignancies. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC Note=Binds 1 Ca(2+) ion 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:0000305}. CC -!- TISSUE SPECIFICITY: Specifically expressed in stromal cells of breast CC carcinomas. 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 -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/200/ST3"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mmp11/"; 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; X57766; CAA40918.1; -; mRNA. DR EMBL; AY899208; AAW65373.1; -; Genomic_DNA. DR EMBL; AP000349; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC057788; AAH57788.1; -; mRNA. DR EMBL; X84664; CAA59150.1; -; Genomic_DNA. DR CCDS; CCDS13816.1; -. DR PIR; S13423; S13423. DR RefSeq; NP_005931.2; NM_005940.4. DR AlphaFoldDB; P24347; -. DR SMR; P24347; -. DR BioGRID; 110463; 8. DR STRING; 9606.ENSP00000215743; -. DR BindingDB; P24347; -. DR ChEMBL; CHEMBL2867; -. DR DrugBank; DB00786; Marimastat. DR DrugBank; DB04318; NAlpha-[(2S)-2-{[(S)-[(1S)-1-{[(Benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl]methyl}-5-phenylpentanoyl]-L-tryptophanamide. DR GuidetoPHARMACOLOGY; 1635; -. DR MEROPS; M10.007; -. DR iPTMnet; P24347; -. DR PhosphoSitePlus; P24347; -. DR BioMuta; MMP11; -. DR DMDM; 317373418; -. DR jPOST; P24347; -. DR MassIVE; P24347; -. DR PaxDb; 9606-ENSP00000215743; -. DR PeptideAtlas; P24347; -. DR ProteomicsDB; 54197; -. DR Antibodypedia; 3609; 600 antibodies from 36 providers. DR DNASU; 4320; -. DR Ensembl; ENST00000215743.8; ENSP00000215743.3; ENSG00000099953.10. DR Ensembl; ENST00000612388.3; ENSP00000483349.1; ENSG00000275365.3. DR GeneID; 4320; -. DR KEGG; hsa:4320; -. DR MANE-Select; ENST00000215743.8; ENSP00000215743.3; NM_005940.5; NP_005931.2. DR UCSC; uc002zxx.4; human. DR AGR; HGNC:7157; -. DR CTD; 4320; -. DR DisGeNET; 4320; -. DR GeneCards; MMP11; -. DR HGNC; HGNC:7157; MMP11. DR HPA; ENSG00000099953; Group enriched (cervix, endometrium, placenta). DR MIM; 185261; gene. DR neXtProt; NX_P24347; -. DR OpenTargets; ENSG00000099953; -. DR PharmGKB; PA30869; -. DR VEuPathDB; HostDB:ENSG00000099953; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00940000156340; -. DR HOGENOM; CLU_015489_8_3_1; -. DR InParanoid; P24347; -. DR OMA; YWRFNPH; -. DR OrthoDB; 2225278at2759; -. DR PhylomeDB; P24347; -. DR TreeFam; TF315428; -. DR BRENDA; 3.4.24.B3; 2681. DR PathwayCommons; P24347; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR SignaLink; P24347; -. DR SIGNOR; P24347; -. DR BioGRID-ORCS; 4320; 13 hits in 1159 CRISPR screens. DR ChiTaRS; MMP11; human. DR GeneWiki; MMP11; -. DR GenomeRNAi; 4320; -. DR Pharos; P24347; Tchem. DR PRO; PR:P24347; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P24347; Protein. DR Bgee; ENSG00000099953; Expressed in stromal cell of endometrium and 100 other cell types or tissues. DR ExpressionAtlas; P24347; baseline and differential. DR GO; GO:0031012; C:extracellular matrix; IDA:MGI. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0071711; P:basement membrane organization; IEA:Ensembl. DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central. DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. 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 PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1. DR PANTHER; PTHR10201:SF20; STROMELYSIN-3; 1. DR Pfam; PF00045; Hemopexin; 4. DR Pfam; PF00413; Peptidase_M10; 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 PROSITE; PS00546; CYSTEINE_SWITCH; 1. DR PROSITE; PS00024; HEMOPEXIN; 1. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P24347; HS. PE 1: Evidence at protein level; KW Calcium; Cleavage on pair of basic residues; Collagen degradation; KW Direct protein sequencing; Disulfide bond; Extracellular matrix; Hydrolase; KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat; KW Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..31 FT /evidence="ECO:0000255" FT PROPEP 32..97 FT /note="Activation peptide" FT /evidence="ECO:0000250" FT /id="PRO_0000028770" FT CHAIN 98..488 FT /note="Stromelysin-3" FT /id="PRO_0000028771" FT REPEAT 291..339 FT /note="Hemopexin 1" FT REPEAT 340..382 FT /note="Hemopexin 2" FT REPEAT 384..432 FT /note="Hemopexin 3" FT REPEAT 433..480 FT /note="Hemopexin 4" FT REGION 41..93 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 78..85 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT ACT_SITE 216 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 80 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 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 /evidence="ECO:0000250" FT BINDING 172 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT BINDING 174 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" 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 192 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 219 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 225 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT DISULFID 294..480 FT /evidence="ECO:0000250" FT VARIANT 38 FT /note="A -> V (in dbSNP:rs738792)" FT /evidence="ECO:0000269|PubMed:1701851, ECO:0000269|Ref.2" FT /id="VAR_022181" FT VARIANT 44 FT /note="E -> K (in dbSNP:rs28363646)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_022182" FT VARIANT 61 FT /note="P -> L (in dbSNP:rs28363647)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_022183" FT VARIANT 86 FT /note="S -> P (in dbSNP:rs28363648)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_022184" FT VARIANT 166 FT /note="D -> N (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036140" FT VARIANT 182 FT /note="F -> S (in dbSNP:rs17854940)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_029659" SQ SEQUENCE 488 AA; 54590 MW; F03C537EE76706A9 CRC64; MAPAAWLRSA AARALLPPML LLLLQPPPLL ARALPPDAHH LHAERRGPQP WHAALPSSPA PAPATQEAPR PASSLRPPRC GVPDPSDGLS ARNRQKRFVL SGGRWEKTDL TYRILRFPWQ LVQEQVRQTM AEALKVWSDV TPLTFTEVHE GRADIMIDFA RYWHGDDLPF DGPGGILAHA FFPKTHREGD VHFDYDETWT IGDDQGTDLL QVAAHEFGHV LGLQHTTAAK ALMSAFYTFR YPLSLSPDDC RGVQHLYGQP WPTVTSRTPA LGPQAGIDTN EIAPLEPDAP PDACEASFDA VSTIRGELFF FKAGFVWRLR GGQLQPGYPA LASRHWQGLP SPVDAAFEDA QGHIWFFQGA QYWVYDGEKP VLGPAPLTEL GLVRFPVHAA LVWGPEKNKI YFFRGRDYWR FHPSTRRVDS PVPRRATDWR GVPSEIDAAF QDADGYAYFL RGRLYWKFDP VKVKALEGFP RLVGPDFFGC AEPANTFL //