MMP11_HUMAN
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 03-AUG-2022, entry version 205.
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="http://atlasgeneticsoncology.org/Genes/ST3ID200.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp11/";
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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; 1.
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; P24347; -.
DR PeptideAtlas; P24347; -.
DR PRIDE; P24347; -.
DR ProteomicsDB; 54197; -.
DR Antibodypedia; 3609; 553 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 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; IYIFSGG; -.
DR OrthoDB; 1075463at2759; -.
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 BioGRID-ORCS; 4320; 13 hits in 1075 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 98 other tissues.
DR ExpressionAtlas; P24347; baseline and differential.
DR Genevisible; P24347; HS.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; 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; IPR028705; Stromelysin-3.
DR PANTHER; PTHR10201:SF20; PTHR10201:SF20; 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; 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 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
