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   24-JAN-2024, entry version 185.
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; 10116-ENSRNOP00000065434; -.
DR   Ensembl; ENSRNOT00000075610.3; ENSRNOP00000065434.1; ENSRNOG00000010947.9.
DR   Ensembl; ENSRNOT00055020294; ENSRNOP00055016353; ENSRNOG00055011907.
DR   Ensembl; ENSRNOT00060047919; ENSRNOP00060039863; ENSRNOG00060027477.
DR   Ensembl; ENSRNOT00065054795; ENSRNOP00065045061; ENSRNOG00065031768.
DR   GeneID; 81707; -.
DR   KEGG; rno:81707; -.
DR   UCSC; RGD:620198; rat.
DR   AGR; RGD:620198; -.
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; DIKVWEG; -.
DR   OrthoDB; 2225278at2759; -.
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 cell types or tissues.
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: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; 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; Q10739; RN.
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
//