MMP17_HUMAN
ID MMP17_HUMAN Reviewed; 603 AA.
AC Q9ULZ9; Q14850;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Matrix metalloproteinase-17;
DE Short=MMP-17;
DE EC=3.4.24.-;
DE AltName: Full=Membrane-type matrix metalloproteinase 4;
DE Short=MT-MMP 4;
DE Short=MTMMP4;
DE AltName: Full=Membrane-type-4 matrix metalloproteinase;
DE Short=MT4-MMP;
DE Short=MT4MMP;
DE Flags: Precursor;
GN Name=MMP17; Synonyms=MT4MMP;
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] (ISOFORM LONG).
RC TISSUE=Monocytic leukemia;
RX PubMed=10471807; DOI=10.1016/s0014-5793(99)01065-0;
RA Kajita M., Kinoh H., Ito N., Takamura A., Itoh Y., Okada A., Sato H.,
RA Seiki M.;
RT "Human membrane type-4 matrix metalloproteinase (MT4-MMP) is encoded by a
RT novel major transcript: isolation of complementary DNA clones for human and
RT mouse mt4-mmp transcripts.";
RL FEBS Lett. 457:353-356(1999).
RN [2]
RP SEQUENCE REVISION TO 41; 44; 202-207; 221 AND 225.
RA Seiki M.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Mammary carcinoma;
RX PubMed=8640782;
RA Puente X.S., Pendas A.M., Llano E., Velasco G., Lopez-Otin C.;
RT "Molecular cloning of a novel membrane-type matrix metalloproteinase from a
RT human breast carcinoma.";
RL Cancer Res. 56:944-949(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 126-299, AND CHARACTERIZATION.
RX PubMed=10551873; DOI=10.1074/jbc.274.46.33043;
RA Wang Y., Johnson A.R., Ye Q.-Z., Dyer R.D.;
RT "Catalytic activities and substrate specificity of the human membrane type
RT 4 matrix metalloproteinase catalytic domain.";
RL J. Biol. Chem. 274:33043-33049(1999).
RN [6]
RP GPI-ANCHOR.
RX PubMed=10567400; DOI=10.1074/jbc.274.48.34260;
RA Itoh Y., Kajita M., Kinoh H., Mori H., Okada A., Seiki M.;
RT "Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a
RT glycosylphosphatidylinositol-anchored proteinase.";
RL J. Biol. Chem. 274:34260-34266(1999).
RN [7]
RP CHARACTERIZATION.
RX PubMed=10543448; DOI=10.1515/bc.1999.137;
RA Kolkenbrock H., Essers L., Ulbrich N., Will H.;
RT "Biochemical characterization of the catalytic domain of membrane-type 4
RT matrix metalloproteinase.";
RL Biol. Chem. 380:1103-1108(1999).
CC -!- FUNCTION: Endopeptidase that degrades various components of the
CC extracellular matrix, such as fibrin. May be involved in the activation
CC of membrane-bound precursors of growth factors or inflammatory
CC mediators, such as tumor necrosis factor-alpha. May also be involved in
CC tumoral process. Cleaves pro-TNF-alpha at the '74-Ala-|-Gln-75' site.
CC Not obvious if able to proteolytically activate progelatinase A. Does
CC not hydrolyze collagen types I, II, III, IV and V, gelatin,
CC fibronectin, laminin, decorin nor alpha1-antitrypsin.
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 -!- SUBCELLULAR LOCATION: [Isoform Long]: Cell membrane; Lipid-anchor, GPI-
CC anchor; Extracellular side. Secreted, extracellular space,
CC extracellular matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q9ULZ9-1; Sequence=Displayed;
CC Name=Short; Synonyms=Puente;
CC IsoId=Q9ULZ9-2; Sequence=VSP_005456;
CC -!- TISSUE SPECIFICITY: Expressed in brain, leukocytes, colon, ovary testis
CC and breast cancer. Expressed also in many transformed and non-
CC transformed cell types.
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 ---------------------------------------------------------------------------
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; AB021225; BAA82707.2; -; mRNA.
DR EMBL; X89576; CAA61753.1; -; mRNA.
DR EMBL; AC131009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS31927.1; -. [Q9ULZ9-1]
DR RefSeq; NP_057239.4; NM_016155.5. [Q9ULZ9-1]
DR RefSeq; XP_011536657.1; XM_011538355.2. [Q9ULZ9-2]
DR RefSeq; XP_011536658.1; XM_011538356.2. [Q9ULZ9-2]
DR RefSeq; XP_011536659.1; XM_011538357.2. [Q9ULZ9-2]
DR AlphaFoldDB; Q9ULZ9; -.
DR SMR; Q9ULZ9; -.
DR BioGRID; 110469; 1.
DR STRING; 9606.ENSP00000353767; -.
DR BindingDB; Q9ULZ9; -.
DR ChEMBL; CHEMBL2937; -.
DR DrugBank; DB00786; Marimastat.
DR GuidetoPHARMACOLOGY; 1641; -.
DR MEROPS; M10.017; -.
DR GlyGen; Q9ULZ9; 2 sites.
DR iPTMnet; Q9ULZ9; -.
DR PhosphoSitePlus; Q9ULZ9; -.
DR BioMuta; MMP17; -.
DR DMDM; 296439485; -.
DR MassIVE; Q9ULZ9; -.
DR PaxDb; Q9ULZ9; -.
DR PeptideAtlas; Q9ULZ9; -.
DR PRIDE; Q9ULZ9; -.
DR ProteomicsDB; 85161; -. [Q9ULZ9-1]
DR ProteomicsDB; 85162; -. [Q9ULZ9-2]
DR Antibodypedia; 31995; 315 antibodies from 31 providers.
DR DNASU; 4326; -.
DR Ensembl; ENST00000360564.5; ENSP00000353767.1; ENSG00000198598.7. [Q9ULZ9-1]
DR Ensembl; ENST00000535291.5; ENSP00000441106.1; ENSG00000198598.7. [Q9ULZ9-2]
DR GeneID; 4326; -.
DR KEGG; hsa:4326; -.
DR MANE-Select; ENST00000360564.5; ENSP00000353767.1; NM_016155.7; NP_057239.4.
DR UCSC; uc001ujc.2; human. [Q9ULZ9-1]
DR CTD; 4326; -.
DR DisGeNET; 4326; -.
DR GeneCards; MMP17; -.
DR HGNC; HGNC:7163; MMP17.
DR HPA; ENSG00000198598; Tissue enhanced (brain).
DR MIM; 602285; gene.
DR neXtProt; NX_Q9ULZ9; -.
DR OpenTargets; ENSG00000198598; -.
DR PharmGKB; PA30875; -.
DR VEuPathDB; HostDB:ENSG00000198598; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000158699; -.
DR InParanoid; Q9ULZ9; -.
DR OMA; WLVCGDP; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9ULZ9; -.
DR TreeFam; TF315428; -.
DR PathwayCommons; Q9ULZ9; -.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR SignaLink; Q9ULZ9; -.
DR BioGRID-ORCS; 4326; 20 hits in 1077 CRISPR screens.
DR GeneWiki; MMP17; -.
DR GenomeRNAi; 4326; -.
DR Pharos; Q9ULZ9; Tchem.
DR PRO; PR:Q9ULZ9; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9ULZ9; protein.
DR Bgee; ENSG00000198598; Expressed in right frontal lobe and 101 other tissues.
DR ExpressionAtlas; Q9ULZ9; baseline and differential.
DR Genevisible; Q9ULZ9; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0042756; P:drinking behavior; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; TAS:ParkinsonsUK-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; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR028726; MMP17.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR PANTHER; PTHR10201:SF21; PTHR10201:SF21; 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; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane;
KW Cleavage on pair of basic residues; Disulfide bond; Extracellular matrix;
KW Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT PROPEP 36..125
FT /evidence="ECO:0000250"
FT /id="PRO_0000028818"
FT CHAIN 126..565
FT /note="Matrix metalloproteinase-17"
FT /id="PRO_0000028819"
FT PROPEP 566..603
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000028820"
FT REPEAT 333..378
FT /note="Hemopexin 1"
FT REPEAT 382..427
FT /note="Hemopexin 2"
FT REPEAT 428..475
FT /note="Hemopexin 3"
FT REPEAT 476..523
FT /note="Hemopexin 4"
FT REGION 301..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 108..115
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 110
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 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 252
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 258
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT LIPID 565
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 332..523
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8640782"
FT /id="VSP_005456"
FT CONFLICT 23
FT /note="L -> LLPL (in Ref. 1; BAA82707 and 2; CAA61753)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="A -> T (in Ref. 1; BAA82707 and 2; CAA61753)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 66653 MW; BB297B21973C7A0B CRC64;
MRRRAARGPG PPPPGPGLSR LPLPLLLLLA LGTRGGCAAP APAPRAEDLS LGVEWLSRFG
YLPPADPTTG QLQTQEELSK AITAMQQFGG LEATGILDEA TLALMKTPRC SLPDLPVLTQ
ARRRRQAPAP TKWNKRNLSW RVRTFPRDSP LGHDTVRALM YYALKVWSDI APLNFHEVAG
SAADIQIDFS KADHNDGYPF DGPGGTVAHA FFPGHHHTAG DTHFDDDEAW TFRSSDAHGM
DLFAVAVHEF GHAIGLSHVA AAHSIMRPYY QGPVGDPLRY GLPYEDKVRV WQLYGVRESV
SPTAQPEEPP LLPEPPDNRS SAPPRKDVPH RCSTHFDAVA QIRGEAFFFK GKYFWRLTRD
RHLVSLQPAQ MHRFWRGLPL HLDSVDAVYE RTSDHKIVFF KGDRYWVFKD NNVEEGYPRP
VSDFSLPPGG IDAAFSWAHN DRTYFFKDQL YWRYDDHTRH MDPGYPAQSP LWRGVPSTLD
DAMRWSDGAS YFFRGQEYWK VLDGELEVAP GYPQSTARDW LVCGDSQADG SVAAGVDAAE
GPRAPPGQHD QSRSEDGYEV CSCTSGASSP PGAPGPLVAA TMLLLLPPLS PGALWTAAQA
LTL
