MMP15_HUMAN
ID MMP15_HUMAN Reviewed; 669 AA.
AC P51511; A0A2U6; Q14111;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Matrix metalloproteinase-15;
DE Short=MMP-15;
DE EC=3.4.24.-;
DE AltName: Full=Membrane-type matrix metalloproteinase 2;
DE Short=MT-MMP 2;
DE Short=MTMMP2;
DE AltName: Full=Membrane-type-2 matrix metalloproteinase;
DE Short=MT2-MMP;
DE Short=MT2MMP;
DE AltName: Full=SMCP-2;
DE Flags: Precursor;
GN Name=MMP15;
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=Lung;
RX PubMed=7649159; DOI=10.1111/j.1432-1033.1995.tb20738.x;
RA Will H., Hinzmann B.;
RT "cDNA sequence and mRNA tissue distribution of a novel human matrix
RT metalloproteinase with a potential transmembrane segment.";
RL Eur. J. Biochem. 231:602-608(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-200; LEU-350; GLY-596;
RP ARG-609 AND TRP-622.
RG NIEHS SNPs program;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 94-669, AND VARIANT ARG-609.
RX PubMed=9119382; DOI=10.1006/geno.1996.4496;
RA Sato H., Tanaka M., Takino T., Inoue M., Seiki M.;
RT "Assignment of the human genes for membrane-type-1, -2, and -3 matrix
RT metalloproteinases (MMP14, MMP15, and MMP16) to 14q12.2, 16q12.2-q21, and
RT 8q21, respectively, by in situ hybridization.";
RL Genomics 39:412-413(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 163-669.
RC TISSUE=Placenta;
RA Shofuda K., Yasumitsu H., Nishihashi A., Miki K., Miyazaki K.;
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION.
RX PubMed=9461298; DOI=10.1111/j.1432-1033.1997.00751.x;
RA d'Ortho M.P., Will H., Atkinson S., Butler G., Messent A., Gavrilovic J.,
RA Smith B., Timpl R., Zardi L., Murphy G.;
RT "Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum
RT proteolytic capacities comparable to many matrix metalloproteinases.";
RL Eur. J. Biochem. 250:751-757(1997).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] GLY-596.
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: Endopeptidase that degrades various components of the
CC extracellular matrix. May activate progelatinase A.
CC {ECO:0000269|PubMed:9461298}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC P51511; P04070: PROC; NbExp=2; IntAct=EBI-1383043, EBI-1383018;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}; Extracellular side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Appeared to be synthesized preferentially in liver,
CC placenta, testis, colon and intestine. Substantial amounts are also
CC detected in pancreas, kidney, lung, heart and skeletal muscle.
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 -!- SEQUENCE CAUTION:
CC Sequence=BAA13071.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp15/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MMP15ID41392ch16q21.html";
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DR EMBL; Z48482; CAA88373.1; -; mRNA.
DR EMBL; EF032329; ABJ53423.1; -; Genomic_DNA.
DR EMBL; BC036495; AAH36495.1; -; mRNA.
DR EMBL; BC055428; AAH55428.1; -; mRNA.
DR EMBL; D86331; BAA13071.1; ALT_INIT; mRNA.
DR EMBL; D85510; BAA22225.1; -; mRNA.
DR CCDS; CCDS10792.1; -.
DR PIR; I38029; I38029.
DR RefSeq; NP_002419.1; NM_002428.3.
DR AlphaFoldDB; P51511; -.
DR SMR; P51511; -.
DR BioGRID; 110467; 44.
DR IntAct; P51511; 5.
DR MINT; P51511; -.
DR STRING; 9606.ENSP00000219271; -.
DR BindingDB; P51511; -.
DR ChEMBL; CHEMBL2963; -.
DR DrugBank; DB00786; Marimastat.
DR GuidetoPHARMACOLOGY; 1639; -.
DR MEROPS; M10.015; -.
DR GlyGen; P51511; 1 site.
DR iPTMnet; P51511; -.
DR PhosphoSitePlus; P51511; -.
DR BioMuta; MMP15; -.
DR DMDM; 1705988; -.
DR EPD; P51511; -.
DR jPOST; P51511; -.
DR MassIVE; P51511; -.
DR MaxQB; P51511; -.
DR PaxDb; P51511; -.
DR PeptideAtlas; P51511; -.
DR PRIDE; P51511; -.
DR ProteomicsDB; 56312; -.
DR Antibodypedia; 3619; 493 antibodies from 37 providers.
DR DNASU; 4324; -.
DR Ensembl; ENST00000219271.4; ENSP00000219271.3; ENSG00000102996.5.
DR GeneID; 4324; -.
DR KEGG; hsa:4324; -.
DR MANE-Select; ENST00000219271.4; ENSP00000219271.3; NM_002428.4; NP_002419.1.
DR UCSC; uc002ena.4; human.
DR CTD; 4324; -.
DR DisGeNET; 4324; -.
DR GeneCards; MMP15; -.
DR HGNC; HGNC:7161; MMP15.
DR HPA; ENSG00000102996; Low tissue specificity.
DR MIM; 602261; gene.
DR neXtProt; NX_P51511; -.
DR OpenTargets; ENSG00000102996; -.
DR PharmGKB; PA30873; -.
DR VEuPathDB; HostDB:ENSG00000102996; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000156939; -.
DR HOGENOM; CLU_015489_8_1_1; -.
DR InParanoid; P51511; -.
DR OMA; EMQKFYG; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; P51511; -.
DR TreeFam; TF352396; -.
DR BRENDA; 3.4.24.B5; 2681.
DR PathwayCommons; P51511; -.
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; P51511; -.
DR BioGRID-ORCS; 4324; 12 hits in 1075 CRISPR screens.
DR GeneWiki; MMP15; -.
DR GenomeRNAi; 4324; -.
DR Pharos; P51511; Tchem.
DR PRO; PR:P51511; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P51511; protein.
DR Bgee; ENSG00000102996; Expressed in mucosa of transverse colon and 114 other tissues.
DR ExpressionAtlas; P51511; baseline and differential.
DR Genevisible; P51511; HS.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR GO; GO:0070006; F:metalloaminopeptidase activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
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; IPR028729; MMP15.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR021805; Pept_M10A_metallopeptidase_C.
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:SF25; PTHR10201:SF25; 1.
DR Pfam; PF11857; DUF3377; 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; 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 Calcium; Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..41
FT /note="Or 45"
FT /evidence="ECO:0000255"
FT PROPEP 42..131
FT /evidence="ECO:0000250"
FT /id="PRO_0000028808"
FT CHAIN 132..669
FT /note="Matrix metalloproteinase-15"
FT /id="PRO_0000028809"
FT TOPO_DOM 132..625
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 647..669
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 367..415
FT /note="Hemopexin 1"
FT REPEAT 416..461
FT /note="Hemopexin 2"
FT REPEAT 463..511
FT /note="Hemopexin 3"
FT REPEAT 512..559
FT /note="Hemopexin 4"
FT REGION 300..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..116
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 331..357
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 263
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:24275569"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 370..559
FT /evidence="ECO:0000250"
FT VARIANT 200
FT /note="L -> P (in dbSNP:rs41340745)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_030523"
FT VARIANT 350
FT /note="P -> L (in dbSNP:rs41335851)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_030524"
FT VARIANT 596
FT /note="D -> G (in dbSNP:rs41504346)"
FT /evidence="ECO:0000269|PubMed:16959974, ECO:0000269|Ref.2"
FT /id="VAR_030525"
FT VARIANT 609
FT /note="G -> R (in dbSNP:rs3743563)"
FT /evidence="ECO:0000269|PubMed:9119382, ECO:0000269|Ref.2"
FT /id="VAR_020055"
FT VARIANT 622
FT /note="R -> W (in dbSNP:rs41434246)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_030526"
SQ SEQUENCE 669 AA; 75807 MW; FE875EC0674B297F CRC64;
MGSDPSAPGR PGWTGSLLGD REEAARPRLL PLLLVLLGCL GLGVAAEDAE VHAENWLRLY
GYLPQPSRHM STMRSAQILA SALAEMQRFY GIPVTGVLDE ETKEWMKRPR CGVPDQFGVR
VKANLRRRRK RYALTGRKWN NHHLTFSIQN YTEKLGWYHS MEAVRRAFRV WEQATPLVFQ
EVPYEDIRLR RQKEADIMVL FASGFHGDSS PFDGTGGFLA HAYFPGPGLG GDTHFDADEP
WTFSSTDLHG NNLFLVAVHE LGHALGLEHS SNPNAIMAPF YQWKDVDNFK LPEDDLRGIQ
QLYGTPDGQP QPTQPLPTVT PRRPGRPDHR PPRPPQPPPP GGKPERPPKP GPPVQPRATE
RPDQYGPNIC DGDFDTVAML RGEMFVFKGR WFWRVRHNRV LDNYPMPIGH FWRGLPGDIS
AAYERQDGRF VFFKGDRYWL FREANLEPGY PQPLTSYGLG IPYDRIDTAI WWEPTGHTFF
FQEDRYWRFN EETQRGDPGY PKPISVWQGI PASPKGAFLS NDAAYTYFYK GTKYWKFDNE
RLRMEPGYPK SILRDFMGCQ EHVEPGPRWP DVARPPFNPH GGAEPGADSA EGDVGDGDGD
FGAGVNKDGG SRVVVQMEEV ARTVNVVMVL VPLLLLLCVL GLTYALVQMQ RKGAPRVLLY
CKRSLQEWV
