MMP14_RAT
ID MMP14_RAT Reviewed; 582 AA.
AC Q10739; Q6IN06;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Matrix metalloproteinase-14;
DE Short=MMP-14;
DE EC=3.4.24.80;
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=MT-MMP;
DE Short=MT1-MMP;
DE Short=MT1MMP;
DE Flags: Precursor;
GN Name=Mmp14; Synonyms=Mtmmp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Cossins J., Clements J., Catlin G., Wells G.;
RT "Expression and function of MT-MMP in glial cells.";
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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).
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. May be involved in
CC actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive
CC regulator of cell growth and migration via activation of MMP15 in
CC association with pro-MMP2. Involved in the formation of the
CC fibrovascular tissues in association with pro-MMP2. Cleaves ADGRB1 to
CC release vasculostatin-40 which inhibits angiogenesis.
CC {ECO:0000250|UniProtKB:P50281, ECO:0000250|UniProtKB:P53690}.
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 {ECO:0000250|UniProtKB:P50281}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Melanosome {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Note=Forms a complex with BST2 and localizes to the
CC cytoplasm. {ECO:0000250}.
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: Tyrosine phosphorylated by PKDCC/VLK.
CC {ECO:0000250|UniProtKB:P50281}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; X83537; CAA58521.1; -; mRNA.
DR EMBL; X91785; CAA62897.1; -; mRNA.
DR EMBL; BC072509; AAH72509.1; -; mRNA.
DR PIR; I84471; I84471.
DR RefSeq; NP_112318.1; NM_031056.1.
DR AlphaFoldDB; Q10739; -.
DR BMRB; Q10739; -.
DR SMR; Q10739; -.
DR STRING; 10116.ENSRNOP00000065434; -.
DR MEROPS; M10.014; -.
DR iPTMnet; Q10739; -.
DR PhosphoSitePlus; Q10739; -.
DR PaxDb; Q10739; -.
DR Ensembl; ENSRNOT00000075610; ENSRNOP00000065434; ENSRNOG00000010947.
DR GeneID; 81707; -.
DR KEGG; rno:81707; -.
DR UCSC; RGD:620198; rat.
DR CTD; 4323; -.
DR RGD; 620198; Mmp14.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000157808; -.
DR HOGENOM; CLU_015489_8_1_1; -.
DR InParanoid; Q10739; -.
DR OMA; VWELRAH; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q10739; -.
DR TreeFam; TF352396; -.
DR BRENDA; 3.4.24.80; 5301.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR PRO; PR:Q10739; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000010947; Expressed in ovary and 19 other tissues.
DR Genevisible; Q10739; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IEA:Ensembl.
DR GO; GO:0044354; C:macropinosome; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; IPI:RGD.
DR GO; GO:0070006; F:metalloaminopeptidase activity; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEP:RGD.
DR GO; GO:0043615; P:astrocyte cell migration; IEP:RGD.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:0035988; P:chondrocyte proliferation; ISO:RGD.
DR GO; GO:0030574; P:collagen catabolic process; ISO:RGD.
DR GO; GO:0097094; P:craniofacial suture morphogenesis; ISO:RGD.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0035987; P:endodermal cell differentiation; ISO:RGD.
DR GO; GO:0001935; P:endothelial cell proliferation; IEP:RGD.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0060322; P:head development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IDA:RGD.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0001503; P:ossification; IEP:RGD.
DR GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:1905523; P:positive regulation of macrophage migration; ISO:RGD.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; IMP:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:1990834; P:response to odorant; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0048771; P:tissue remodeling; IDA:RGD.
DR GO; GO:0031638; P:zymogen activation; ISO:RGD.
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 2: Evidence at transcript level;
KW Calcium; Cleavage on pair of basic residues; Cytoplasm; Disulfide bond;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..111
FT /note="Activation peptide"
FT /id="PRO_0000028806"
FT CHAIN 112..582
FT /note="Matrix metalloproteinase-14"
FT /id="PRO_0000028807"
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 280..317
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 /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 BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT MOD_RES 399
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000250|UniProtKB:P50281"
FT DISULFID 319..508
FT /evidence="ECO:0000250"
FT CONFLICT 68
FT /note="M -> I (in Ref. 1; CAA58521)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="A -> D (in Ref. 1; CAA58521)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 582 AA; 66080 MW; 48F1A8E3065E1AE8 CRC64;
MSPAPRPSRS LLLPLLTLGT TLASLGWAQS SNFSPEAWLQ QYGYLPPGDL RTHTQRSPQS
LSAAIAAMQR FYGLQVTGKA DSDTMKAMRR PRCGVPDKFG TEIKANVRRK RYAIQGLKWQ
HNEITFCIQN YTPKVGEYAT FEAIRKAFRV WESATPLRFR EVPYAYIREG HEKQADIMIL
FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVQNEDLNG NDIFLVAVHE
LGHALGLEHS NDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGSKSGSP TKMPPQPRTT
SRPSVPDKPR NPTYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM DGYPMPIGQF
WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF
WMPNGKTYFF RGNKYYRFNE EFRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG
NKYWKFNNQK LKVEPGYPKS ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGSGAVSAA
AVVLPVLLLL LVLAVGLAVF FFRRHGTPKR LLYCQRSLLD KV
