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 27-MAR-2024, entry version 230. 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="https://atlasgeneticsoncology.org/gene/41391/MMP14"; 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; 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; 64. 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 GlyCosmos; P50281; 1 site, 1 glycan. DR GlyGen; P50281; 7 sites, 2 O-linked glycans (7 sites). 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; 9606-ENSP00000308208; -. DR PeptideAtlas; P50281; -. DR ProteomicsDB; 56213; -. DR Pumba; P50281; -. DR ABCD; P50281; 1 sequenced antibody. DR Antibodypedia; 4088; 1159 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 AGR; HGNC:7160; -. 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; DIKVWEG; -. DR OrthoDB; 2225278at2759; -. DR PhylomeDB; P50281; -. DR TreeFam; TF352396; -. DR BioCyc; MetaCyc:ENSG00000157227-MONOMER; -. 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 1164 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 163 other cell types or tissues. DR ExpressionAtlas; P50281; baseline and differential. 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: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; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 1. DR Gene3D; 1.10.101.10; PGBD-like superfamily/PGBD; 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 PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1. DR PANTHER; PTHR10201:SF24; MATRIX METALLOPROTEINASE-14; 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; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF47090; PGBD-like; 1. DR PROSITE; PS00546; CYSTEINE_SWITCH; 1. DR PROSITE; PS00024; HEMOPEXIN; 1. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; P50281; HS. 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 proteasomal 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 //