MMP14_HUMAN
ID MMP14_HUMAN Reviewed; 582 AA.
AC P50281; A8K5L0; Q6GSF3; Q92678;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Matrix metalloproteinase-14;
DE Short=MMP-14;
DE EC=3.4.24.80;
DE AltName: Full=MMP-X1;
DE AltName: Full=Membrane-type matrix metalloproteinase 1;
DE Short=MT-MMP 1;
DE Short=MTMMP1;
DE AltName: Full=Membrane-type-1 matrix metalloproteinase;
DE Short=MT1-MMP;
DE Short=MT1MMP;
DE Flags: Precursor;
GN Name=MMP14;
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 SER-8.
RC TISSUE=Placenta;
RX PubMed=8015608; DOI=10.1038/370061a0;
RA Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M.;
RT "A matrix metalloproteinase expressed on the surface of invasive tumour
RT cells.";
RL Nature 370:61-65(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-8.
RC TISSUE=Placenta;
RX PubMed=7721107; DOI=10.1016/0378-1119(94)00637-8;
RA Takino T., Sato H., Yamamoto E., Seiki M.;
RT "Cloning of a human gene potentially encoding a novel matrix
RT metalloproteinase having a C-terminal transmembrane domain.";
RL Gene 155:293-298(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-8.
RX PubMed=7708715; DOI=10.1073/pnas.92.7.2730;
RA Okada A., Bellocq J.-P., Rouyer N., Chenard M.P., Rio M.C., Chambon P.,
RA Basset P.;
RT "Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in
RT stromal cells of human colon, breast, and head and neck carcinomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2730-2734(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-8.
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Luo G.-X., Reisfeld R.A., Strongin A.Y.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8706726; DOI=10.1111/j.1432-1033.1996.0239u.x;
RA Lohi J.L., Westermarck J., Kaehaeri V.M., Keski-Oja J.;
RT "Regulation of membrane-type matrix metalloproteinase-1 expression by
RT growth factors and phorbol 12-myristate 13-acetate.";
RL Eur. J. Biochem. 239:239-247(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-8.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-4; LYS-6; SER-8;
RP VAL-233; ASN-273; TRP-302 AND ILE-355.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-8.
RC TISSUE=Skin;
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 [11]
RP PROTEIN SEQUENCE OF 112-116.
RX PubMed=8804434; DOI=10.1016/0014-5793(96)00861-7;
RA Sato H., Kinoshita T., Takino T., Nakayama K., Seiki M.;
RT "Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-
RT MMP) by furin and its interaction with tissue inhibitor of
RT metalloproteinases (TIMP)-2.";
RL FEBS Lett. 393:101-104(1996).
RN [12]
RP FUNCTION IN THE FORMATION OF THE FIBROVASCULAR TISSUES.
RX PubMed=12714657; DOI=10.1167/iovs.02-0662;
RA Noda K., Ishida S., Inoue M., Obata K., Oguchi Y., Okada Y., Ikeda E.;
RT "Production and activation of matrix metalloproteinase-2 in proliferative
RT diabetic retinopathy.";
RL Invest. Ophthalmol. Vis. Sci. 44:2163-2170(2003).
RN [13]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [14]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=18223680; DOI=10.1038/sj.onc.1211035;
RA Bonnomet A., Polette M., Strumane K., Gilles C., Dalstein V., Kileztky C.,
RA Berx G., van Roy F., Birembaut P., Nawrocki-Raby B.;
RT "The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by
RT upregulating MT1-MMP expression.";
RL Oncogene 27:3692-3699(2008).
RN [15]
RP FUNCTION.
RX PubMed=20837484; DOI=10.1074/jbc.m110.165159;
RA Golubkov V.S., Chekanov A.V., Cieplak P., Aleshin A.E., Chernov A.V.,
RA Zhu W., Radichev I.A., Zhang D., Dong P.D., Strongin A.Y.;
RT "The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly
RT efficient proteolytic target of membrane type-1 matrix metalloproteinase:
RT implications in cancer and embryogenesis.";
RL J. Biol. Chem. 285:35740-35749(2010).
RN [16]
RP INTERACTION WITH DLL1.
RX PubMed=21572390; DOI=10.1038/emboj.2011.136;
RA Jin G., Zhang F., Chan K.M., Xavier Wong H.L., Liu B., Cheah K.S., Liu X.,
RA Mauch C., Liu D., Zhou Z.;
RT "MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain
RT normal B-cell development.";
RL EMBO J. 30:2281-2293(2011).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BST2.
RX PubMed=22065321; DOI=10.1002/jcb.23433;
RA Gu G., Zhao D., Yin Z., Liu P.;
RT "BST-2 binding with cellular MT1-MMP blocks cell growth and migration via
RT decreasing MMP2 activity.";
RL J. Cell. Biochem. 113:1013-1021(2012).
RN [18]
RP FUNCTION.
RX PubMed=22330140; DOI=10.1038/onc.2012.1;
RA Cork S.M., Kaur B., Devi N.S., Cooper L., Saltz J.H., Sandberg E.M.,
RA Kaluz S., Van Meir E.G.;
RT "A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa
RT vasculostatin from tumor suppressor BAI1.";
RL Oncogene 31:5144-5152(2012).
RN [19]
RP PHOSPHORYLATION AT TYR-399.
RX PubMed=25171405; DOI=10.1016/j.cell.2014.06.048;
RA Bordoli M.R., Yum J., Breitkopf S.B., Thon J.N., Italiano J.E. Jr.,
RA Xiao J., Worby C., Wong S.K., Lin G., Edenius M., Keller T.L., Asara J.M.,
RA Dixon J.E., Yeo C.Y., Whitman M.;
RT "A secreted tyrosine kinase acts in the extracellular environment.";
RL Cell 158:1033-1044(2014).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 114-287 IN COMPLEX WITH TIMP2.
RX PubMed=9724659; DOI=10.1093/emboj/17.17.5238;
RA Fernandez-Catalan C., Bode W., Huber R., Turk D., Calvete J.J., Lichte A.,
RA Tschesche H., Maskos K.;
RT "Crystal structure of the complex formed by the membrane type 1-matrix
RT metalloproteinase with the tissue inhibitor of metalloproteinases-2, the
RT soluble progelatinase A receptor.";
RL EMBO J. 17:5238-5248(1998).
RN [21]
RP VARIANT WNCHRS ARG-17, AND CHARACTERIZATION OF VARIANT WNCHRS ARG-17.
RX PubMed=22922033; DOI=10.1016/j.ajhg.2012.07.022;
RA Evans B.R., Mosig R.A., Lobl M., Martignetti C.R., Camacho C.,
RA Grum-Tokars V., Glucksman M.J., Martignetti J.A.;
RT "Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the
RT multicentric osteolysis and arthritis disease Winchester syndrome.";
RL Am. J. Hum. Genet. 91:572-576(2012).
CC -!- FUNCTION: Endopeptidase that degrades various components of the
CC extracellular matrix such as collagen. Activates progelatinase A.
CC Essential for pericellular collagenolysis and modeling of skeletal and
CC extraskeletal connective tissues during development (By similarity).
CC May be involved in actin cytoskeleton reorganization by cleaving PTK7
CC (PubMed:20837484). Acts as a positive regulator of cell growth and
CC migration via activation of MMP15. Involved in the formation of the
CC fibrovascular tissues in association with pro-MMP2 (PubMed:12714657).
CC Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis
CC (PubMed:22330140). {ECO:0000250|UniProtKB:P53690,
CC ECO:0000269|PubMed:12714657, ECO:0000269|PubMed:20837484,
CC ECO:0000269|PubMed:22065321, ECO:0000269|PubMed:22330140}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endopeptidase activity. Activates progelatinase A by cleavage
CC of the propeptide at 37-Asn-|-Leu-38. Other bonds hydrolyzed include
CC 35-Gly-|-Ile-36 in the propeptide of collagenase 3, and 341-Asn-|-
CC Phe-342, 441-Asp-|-Leu-442 and 354-Gln-|-Thr-355 in the aggrecan
CC interglobular domain.; EC=3.4.24.80;
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 -!- SUBUNIT: Interacts (via C-terminal cytoplasmic tail) with BST2.
CC Interacts with DLL1; inhibits DLL1-induced Notch signaling
CC (PubMed:21572390). {ECO:0000269|PubMed:21572390,
CC ECO:0000269|PubMed:22065321, ECO:0000269|PubMed:9724659}.
CC -!- INTERACTION:
CC P50281; Q9BV57: ADI1; NbExp=4; IntAct=EBI-992788, EBI-992807;
CC P50281; Q13520: AQP6; NbExp=3; IntAct=EBI-992788, EBI-13059134;
CC P50281; P56945: BCAR1; NbExp=3; IntAct=EBI-992788, EBI-702093;
CC P50281; Q15125: EBP; NbExp=3; IntAct=EBI-992788, EBI-3915253;
CC P50281; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-992788, EBI-18535450;
CC P50281; Q9Y624: F11R; NbExp=3; IntAct=EBI-992788, EBI-742600;
CC P50281; P22455: FGFR4; NbExp=6; IntAct=EBI-992788, EBI-6256193;
CC P50281; Q13643: FHL3; NbExp=3; IntAct=EBI-992788, EBI-741101;
CC P50281; P09958: FURIN; NbExp=3; IntAct=EBI-992788, EBI-1056807;
CC P50281; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-992788, EBI-18053395;
CC P50281; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-992788, EBI-749265;
CC P50281; P53667: LIMK1; NbExp=4; IntAct=EBI-992788, EBI-444403;
CC P50281; P51884: LUM; NbExp=2; IntAct=EBI-992788, EBI-725780;
CC P50281; Q15800: MSMO1; NbExp=3; IntAct=EBI-992788, EBI-949102;
CC P50281; P27105: STOM; NbExp=3; IntAct=EBI-992788, EBI-1211440;
CC P50281; P16035: TIMP2; NbExp=2; IntAct=EBI-992788, EBI-1033507;
CC P50281; Q96AP4: ZUP1; NbExp=3; IntAct=EBI-992788, EBI-744706;
CC P50281; Q9R064: Gorasp2; Xeno; NbExp=14; IntAct=EBI-992788, EBI-4422912;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Melanosome. Cytoplasm. Note=Identified
CC by mass spectrometry in melanosome fractions from stage I to stage IV.
CC Forms a complex with BST2 and localizes to the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in stromal cells of colon, breast, and
CC head and neck. Expressed in lung tumors. {ECO:0000269|PubMed:18223680}.
CC -!- INDUCTION: Up-regulated by NANOS1. {ECO:0000269|PubMed:18223680}.
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 -!- PTM: Tyrosine phosphorylated by PKDCC/VLK.
CC {ECO:0000269|PubMed:25171405}.
CC -!- DISEASE: Winchester syndrome (WNCHRS) [MIM:277950]: A disease
CC characterized by severe osteolysis in the hands and feet, generalized
CC osteoporosis, bone thinning, and absence of subcutaneous nodules.
CC Various additional features include coarse face, corneal opacities, gum
CC hypertrophy, and EKG changes. {ECO:0000269|PubMed:22922033}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp14/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MMP14ID41391ch14q11.html";
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DR EMBL; D26512; BAA05519.1; -; mRNA.
DR EMBL; X83535; CAA58519.1; -; mRNA.
DR EMBL; Z48481; CAA88372.1; -; mRNA.
DR EMBL; U41078; AAA83770.1; -; mRNA.
DR EMBL; X90925; CAA62432.1; -; mRNA.
DR EMBL; AK291325; BAF84014.1; -; mRNA.
DR EMBL; AY795074; AAV40837.1; -; Genomic_DNA.
DR EMBL; AL135998; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064803; AAH64803.1; -; mRNA.
DR CCDS; CCDS9577.1; -.
DR PIR; I38028; I38028.
DR RefSeq; NP_004986.1; NM_004995.3.
DR PDB; 1BQQ; X-ray; 2.75 A; M=114-287.
DR PDB; 1BUV; X-ray; 2.75 A; M=114-287.
DR PDB; 2MQS; NMR; -; A=316-511.
DR PDB; 3C7X; X-ray; 1.70 A; A=316-511.
DR PDB; 3MA2; X-ray; 2.05 A; A/D=112-292.
DR PDB; 3X23; X-ray; 2.40 A; B=563-582.
DR PDB; 4P3C; X-ray; 1.94 A; M=215-227.
DR PDB; 4P3D; X-ray; 1.95 A; C/M=215-227.
DR PDB; 4QXU; X-ray; 2.30 A; K=218-228.
DR PDB; 5H0U; X-ray; 2.24 A; A=116-285.
DR PDB; 6CLZ; NMR; -; A=316-511.
DR PDB; 6CM1; NMR; -; A=316-511.
DR PDBsum; 1BQQ; -.
DR PDBsum; 1BUV; -.
DR PDBsum; 2MQS; -.
DR PDBsum; 3C7X; -.
DR PDBsum; 3MA2; -.
DR PDBsum; 3X23; -.
DR PDBsum; 4P3C; -.
DR PDBsum; 4P3D; -.
DR PDBsum; 4QXU; -.
DR PDBsum; 5H0U; -.
DR PDBsum; 6CLZ; -.
DR PDBsum; 6CM1; -.
DR AlphaFoldDB; P50281; -.
DR BMRB; P50281; -.
DR SMR; P50281; -.
DR BioGRID; 110466; 56.
DR CORUM; P50281; -.
DR DIP; DIP-35111N; -.
DR IntAct; P50281; 49.
DR MINT; P50281; -.
DR STRING; 9606.ENSP00000308208; -.
DR BindingDB; P50281; -.
DR ChEMBL; CHEMBL3869; -.
DR DrugBank; DB00786; Marimastat.
DR DrugCentral; P50281; -.
DR GuidetoPHARMACOLOGY; 1638; -.
DR MEROPS; M10.014; -.
DR TCDB; 8.B.14.2.3; the sea anemone peptide toxin, class 1 (bgk) family.
DR GlyGen; P50281; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50281; -.
DR PhosphoSitePlus; P50281; -.
DR SwissPalm; P50281; -.
DR BioMuta; MMP14; -.
DR DMDM; 317373419; -.
DR EPD; P50281; -.
DR jPOST; P50281; -.
DR MassIVE; P50281; -.
DR MaxQB; P50281; -.
DR PaxDb; P50281; -.
DR PeptideAtlas; P50281; -.
DR PRIDE; P50281; -.
DR ProteomicsDB; 56213; -.
DR ABCD; P50281; 1 sequenced antibody.
DR Antibodypedia; 4088; 1035 antibodies from 45 providers.
DR DNASU; 4323; -.
DR Ensembl; ENST00000311852.11; ENSP00000308208.6; ENSG00000157227.14.
DR GeneID; 4323; -.
DR KEGG; hsa:4323; -.
DR MANE-Select; ENST00000311852.11; ENSP00000308208.6; NM_004995.4; NP_004986.1.
DR UCSC; uc001whc.5; human.
DR CTD; 4323; -.
DR DisGeNET; 4323; -.
DR GeneCards; MMP14; -.
DR HGNC; HGNC:7160; MMP14.
DR HPA; ENSG00000157227; Low tissue specificity.
DR MalaCards; MMP14; -.
DR MIM; 277950; phenotype.
DR MIM; 600754; gene.
DR neXtProt; NX_P50281; -.
DR OpenTargets; ENSG00000157227; -.
DR Orphanet; 371428; Multicentric osteolysis-nodulosis-arthropathy spectrum.
DR PharmGKB; PA30872; -.
DR VEuPathDB; HostDB:ENSG00000157227; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000157808; -.
DR HOGENOM; CLU_015489_8_1_1; -.
DR InParanoid; P50281; -.
DR OMA; VWELRAH; -.
DR OrthoDB; 881347at2759; -.
DR PhylomeDB; P50281; -.
DR TreeFam; TF352396; -.
DR BioCyc; MetaCyc:ENSG00000157227-MON; -.
DR BRENDA; 3.4.24.80; 2681.
DR BRENDA; 3.4.24.B5; 2681.
DR PathwayCommons; P50281; -.
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; P50281; -.
DR SIGNOR; P50281; -.
DR BioGRID-ORCS; 4323; 13 hits in 1082 CRISPR screens.
DR ChiTaRS; MMP14; human.
DR EvolutionaryTrace; P50281; -.
DR GeneWiki; MMP14; -.
DR GenomeRNAi; 4323; -.
DR Pharos; P50281; Tchem.
DR PRO; PR:P50281; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P50281; protein.
DR Bgee; ENSG00000157227; Expressed in stromal cell of endometrium and 162 other tissues.
DR ExpressionAtlas; P50281; baseline and differential.
DR Genevisible; P50281; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IMP:CAFA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0044354; C:macropinosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IMP:CAFA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0043615; P:astrocyte cell migration; IEA:Ensembl.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR GO; GO:0048870; P:cell motility; TAS:ParkinsonsUK-UCL.
DR GO; GO:0035988; P:chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0097094; P:craniofacial suture morphogenesis; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; 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:0060322; P:head development; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IEA:Ensembl.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:1905523; P:positive regulation of macrophage migration; IEA:Ensembl.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; IEA:Ensembl.
DR GO; GO:0016485; P:protein processing; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:1990834; P:response to odorant; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0048771; P:tissue remodeling; IEA:Ensembl.
DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 1.10.101.10; -; 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; 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 InterPro; IPR036366; PGBDSf.
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 3D-structure; Calcium; Cleavage on pair of basic residues; Cytoplasm;
KW Direct protein sequencing; Disease variant; Disulfide bond; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..111
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:8804434"
FT /id="PRO_0000028798"
FT CHAIN 112..582
FT /note="Matrix metalloproteinase-14"
FT /id="PRO_0000028799"
FT TOPO_DOM 112..541
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..582
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 316..364
FT /note="Hemopexin 1"
FT REPEAT 365..410
FT /note="Hemopexin 2"
FT REPEAT 412..460
FT /note="Hemopexin 3"
FT REPEAT 461..508
FT /note="Hemopexin 4"
FT REGION 284..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 91..98
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 93
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 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT MOD_RES 399
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000303|PubMed:25171405"
FT DISULFID 319..508
FT /evidence="ECO:0000250"
FT VARIANT 4
FT /note="A -> T (in dbSNP:rs17882219)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021029"
FT VARIANT 6
FT /note="R -> K (in dbSNP:rs17884647)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021030"
FT VARIANT 8
FT /note="P -> S (in dbSNP:rs1042703)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7649159,
FT ECO:0000269|PubMed:7708715, ECO:0000269|PubMed:7721107,
FT ECO:0000269|PubMed:8015608, ECO:0000269|Ref.8"
FT /id="VAR_021031"
FT VARIANT 17
FT /note="T -> R (in WNCHRS; results in increased MMP14
FT proteosomal degradation and reduced protein localization to
FT cell membrane; dbSNP:rs587777039)"
FT /evidence="ECO:0000269|PubMed:22922033"
FT /id="VAR_070567"
FT VARIANT 233
FT /note="I -> V (in dbSNP:rs17884841)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021032"
FT VARIANT 273
FT /note="D -> N (in dbSNP:rs1042704)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021033"
FT VARIANT 302
FT /note="R -> W (in dbSNP:rs17884719)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021034"
FT VARIANT 355
FT /note="M -> I (in dbSNP:rs17880989)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021035"
FT VARIANT 431
FT /note="R -> H (in dbSNP:rs3751489)"
FT /id="VAR_031267"
FT CONFLICT 338
FT /note="E -> K (in Ref. 1; BAA05519)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="S -> P (in Ref. 6; CAA62432)"
FT /evidence="ECO:0000305"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:3MA2"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:3MA2"
FT HELIX 137..154
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:3MA2"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:1BQQ"
FT STRAND 176..182
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 194..202
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:5H0U"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:5H0U"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3MA2"
FT HELIX 233..244
FT /evidence="ECO:0007829|PDB:3MA2"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:3MA2"
FT HELIX 273..283
FT /evidence="ECO:0007829|PDB:3MA2"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 332..337
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:3C7X"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 370..373
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:2MQS"
FT STRAND 379..383
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 386..391
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:6CM1"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:3C7X"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 416..420
FT /evidence="ECO:0007829|PDB:3C7X"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 427..431
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 434..439
FT /evidence="ECO:0007829|PDB:3C7X"
FT TURN 440..443
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:3C7X"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:6CLZ"
FT STRAND 464..468
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 472..479
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 482..487
FT /evidence="ECO:0007829|PDB:3C7X"
FT TURN 488..491
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:6CLZ"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:3C7X"
FT STRAND 569..575
FT /evidence="ECO:0007829|PDB:3X23"
SQ SEQUENCE 582 AA; 65894 MW; 3722DE286A4BBCDE CRC64;
MSPAPRPPRC LLLPLLTLGT ALASLGSAQS SSFSPEAWLQ QYGYLPPGDL RTHTQRSPQS
LSAAIAAMQK FYGLQVTGKA DADTMKAMRR PRCGVPDKFG AEIKANVRRK RYAIQGLKWQ
HNEITFCIQN YTPKVGEYAT YEAIRKAFRV WESATPLRFR EVPYAYIREG HEKQADIMIF
FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVRNEDLNG NDIFLVAVHE
LGHALGLEHS SDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGGESGFP TKMPPQPRTT
SRPSVPDKPK NPTYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM DGYPMPIGQF
WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF
WMPNGKTYFF RGNKYYRFNE ELRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG
NKYWKFNNQK LKVEPGYPKS ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGGGAVSAA
AVVLPVLLLL LVLAVGLAVF FFRRHGTPRR LLYCQRSLLD KV
