MMP25_HUMAN
ID MMP25_HUMAN Reviewed; 562 AA.
AC Q9NPA2; D3DUA8; Q9H3Q0;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Matrix metalloproteinase-25;
DE Short=MMP-25;
DE EC=3.4.24.-;
DE AltName: Full=Leukolysin;
DE AltName: Full=Membrane-type matrix metalloproteinase 6;
DE Short=MT-MMP 6;
DE Short=MTMMP6;
DE AltName: Full=Membrane-type-6 matrix metalloproteinase;
DE Short=MT6-MMP;
DE Short=MT6MMP;
DE Flags: Precursor;
GN Name=MMP25; Synonyms=MMP20, MMPL1, MT6MMP;
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=Fetal liver;
RX PubMed=10706098;
RA Velasco G., Cal S., Merlos-Suarez A., Ferrando A.A., Alvarez S., Nakano A.,
RA Arribas J., Lopez-Otin C.;
RT "Human MT6-matrix metalloproteinase: identification, progelatinase A
RT activation, and expression in brain tumors.";
RL Cancer Res. 60:877-882(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10628838; DOI=10.1038/sj.cr.7290028;
RA Pei D.Q.;
RT "Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically
RT expressed in the leukocyte lineage.";
RL Cell Res. 9:291-303(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND GPI-ANCHOR.
RX PubMed=11034316; DOI=10.1016/s0014-5793(00)01919-0;
RA Kojima S., Itoh Y., Matsumoto S., Masuho Y., Seiki M.;
RT "Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second
RT glycosyl-phosphatidyl inositol (GPI)-anchored MMP.";
RL FEBS Lett. 480:142-146(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA de Saint-Vis B.M., Clair-Moninot V.A., Lambert C.A., Vanbervliet B.,
RA Pin J.J., Chalus L., Ait-Yahia S., Caux C., Richelle-Nusgens B.V.,
RA Fossiez F., Lebecque S.;
RT "Molecular cloning of a novel human membrane-type matrix metalloproteinase
RT (MT-MMP) predominantly expressed in dendritic cells.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: May activate progelatinase A.
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 Q9NPA2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12346397, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC Extracellular side. Secreted, extracellular space, extracellular
CC matrix.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in leukocytes, lung and
CC spleen. Expressed also in colon carcinoma, astrocytoma and
CC glioblastomas.
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}.
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DR EMBL; AJ239053; CAB94713.1; -; mRNA.
DR EMBL; AF145442; AAF66697.2; -; mRNA.
DR EMBL; AF185270; AAG17007.1; -; mRNA.
DR EMBL; AB042328; BAB20584.1; -; mRNA.
DR EMBL; AJ272137; CAC03490.1; -; mRNA.
DR EMBL; CH471112; EAW85413.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85415.1; -; Genomic_DNA.
DR CCDS; CCDS10492.1; -.
DR RefSeq; NP_071913.1; NM_022468.4.
DR AlphaFoldDB; Q9NPA2; -.
DR SMR; Q9NPA2; -.
DR BioGRID; 122149; 15.
DR IntAct; Q9NPA2; 3.
DR STRING; 9606.ENSP00000337816; -.
DR BindingDB; Q9NPA2; -.
DR ChEMBL; CHEMBL1795103; -.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB13873; Fenofibric acid.
DR DrugBank; DB00786; Marimastat.
DR GuidetoPHARMACOLOGY; 1647; -.
DR MEROPS; M10.024; -.
DR GlyGen; Q9NPA2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NPA2; -.
DR PhosphoSitePlus; Q9NPA2; -.
DR BioMuta; MMP25; -.
DR DMDM; 12585274; -.
DR EPD; Q9NPA2; -.
DR MassIVE; Q9NPA2; -.
DR PaxDb; Q9NPA2; -.
DR PeptideAtlas; Q9NPA2; -.
DR PRIDE; Q9NPA2; -.
DR ProteomicsDB; 81949; -.
DR Antibodypedia; 10685; 308 antibodies from 29 providers.
DR DNASU; 64386; -.
DR Ensembl; ENST00000336577.9; ENSP00000337816.4; ENSG00000008516.18.
DR GeneID; 64386; -.
DR KEGG; hsa:64386; -.
DR MANE-Select; ENST00000336577.9; ENSP00000337816.4; NM_022468.5; NP_071913.1.
DR UCSC; uc002cth.4; human.
DR CTD; 64386; -.
DR DisGeNET; 64386; -.
DR GeneCards; MMP25; -.
DR HGNC; HGNC:14246; MMP25.
DR HPA; ENSG00000008516; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 608482; gene.
DR neXtProt; NX_Q9NPA2; -.
DR OpenTargets; ENSG00000008516; -.
DR PharmGKB; PA30882; -.
DR VEuPathDB; HostDB:ENSG00000008516; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000159799; -.
DR HOGENOM; CLU_015489_8_2_1; -.
DR InParanoid; Q9NPA2; -.
DR OMA; FFFKGPY; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9NPA2; -.
DR TreeFam; TF315428; -.
DR PathwayCommons; Q9NPA2; -.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9NPA2; -.
DR SIGNOR; Q9NPA2; -.
DR BioGRID-ORCS; 64386; 18 hits in 1069 CRISPR screens.
DR GeneWiki; MMP25; -.
DR GenomeRNAi; 64386; -.
DR Pharos; Q9NPA2; Tchem.
DR PRO; PR:Q9NPA2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NPA2; protein.
DR Bgee; ENSG00000008516; Expressed in blood and 158 other tissues.
DR ExpressionAtlas; Q9NPA2; baseline and differential.
DR Genevisible; Q9NPA2; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0060022; P:hard palate development; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; NAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB.
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; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
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; SSF50923; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW Extracellular matrix; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein;
KW Membrane; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..107
FT /evidence="ECO:0000250"
FT /id="PRO_0000028852"
FT CHAIN 108..539
FT /note="Matrix metalloproteinase-25"
FT /id="PRO_0000028853"
FT PROPEP 540..562
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000028854"
FT REPEAT 314..363
FT /note="Hemopexin 1"
FT REPEAT 367..412
FT /note="Hemopexin 2"
FT REPEAT 413..461
FT /note="Hemopexin 3"
FT REPEAT 462..508
FT /note="Hemopexin 4"
FT REGION 278..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 88..95
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 290..309
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 90
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 233
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 237
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT LIPID 539
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT DISULFID 317..508
FT /evidence="ECO:0000250"
FT CONFLICT 47
FT /note="P -> R (in Ref. 3; BAB20584)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 562 AA; 62554 MW; A6A50AE05D969C64 CRC64;
MRLRLRLLAL LLLLLAPPAR APKPSAQDVS LGVDWLTRYG YLPPPHPAQA QLQSPEKLRD
AIKVMQRFAG LPETGRMDPG TVATMRKPRC SLPDVLGVAG LVRRRRRYAL SGSVWKKRTL
TWRVRSFPQS SQLSQETVRV LMSYALMAWG MESGLTFHEV DSPQGQEPDI LIDFARAFHQ
DSYPFDGLGG TLAHAFFPGE HPISGDTHFD DEETWTFGSK DGEGTDLFAV AVHEFGHALG
LGHSSAPNSI MRPFYQGPVG DPDKYRLSQD DRDGLQQLYG KAPQTPYDKP TRKPLAPPPQ
PPASPTHSPS FPIPDRCEGN FDAIANIRGE TFFFKGPWFW RLQPSGQLVS PRPARLHRFW
EGLPAQVRVV QAAYARHRDG RILLFSGPQF WVFQDRQLEG GARPLTELGL PPGEEVDAVF
SWPQNGKTYL VRGRQYWRYD EAAARPDPGY PRDLSLWEGA PPSPDDVTVS NAGDTYFFKG
AHYWRFPKNS IKTEPDAPQP MGPNWLDCPA PSSGPRAPRP PKATPVSETC DCQCELNQAA
GRWPAPIPLL LLPLLVGGVA SR
