MMP14_BOVIN
ID MMP14_BOVIN Reviewed; 582 AA.
AC Q9GLE4;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 127.
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=MT1-MMP;
DE Short=MT1MMP;
DE Flags: Precursor;
GN Name=MMP14;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang B., Yan L., Moses M.A., Fang J., Miao H., Tsang P.;
RT "Molecular cloning and biological characterization of bovine membrane-type
RT matrix metalloprotease 1 (bMT1-MMP).";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
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: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
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; AF290429; AAG28170.1; -; mRNA.
DR RefSeq; NP_776815.1; NM_174390.2.
DR AlphaFoldDB; Q9GLE4; -.
DR SMR; Q9GLE4; -.
DR STRING; 9913.ENSBTAP00000019744; -.
DR MEROPS; M10.014; -.
DR PaxDb; Q9GLE4; -.
DR PRIDE; Q9GLE4; -.
DR GeneID; 281915; -.
DR KEGG; bta:281915; -.
DR CTD; 4323; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; Q9GLE4; -.
DR OrthoDB; 1075463at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:AgBase.
DR GO; GO:0016477; P:cell migration; ISS:AgBase.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0030324; P:lung development; ISS:AgBase.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0031638; P:zymogen activation; ISS:AgBase.
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..110
FT /note="Activation peptide"
FT /id="PRO_0000289295"
FT CHAIN 111..582
FT /note="Matrix metalloproteinase-14"
FT /id="PRO_0000289296"
FT TOPO_DOM 111..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 315..363
FT /note="Hemopexin 1"
FT REPEAT 364..409
FT /note="Hemopexin 2"
FT REPEAT 411..459
FT /note="Hemopexin 3"
FT REPEAT 460..507
FT /note="Hemopexin 4"
FT REGION 279..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 90..97
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 239
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 92
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 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
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 MOD_RES 398
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000250|UniProtKB:P50281"
FT DISULFID 318..507
FT /evidence="ECO:0000250"
SQ SEQUENCE 582 AA; 65883 MW; 65174CE65D4040E1 CRC64;
MSPAPRPACS LLLPVLTLAS ALASLSSAQS SFSPEAWLQQ HGYLPPGDLR THTQRSPQSL
SAAIAAMQRF YGLRVTGKAD ADTMKAMRRP RCGVPDKFGA EIKANVRRKR YAIQGLKWQH
NEITFCIQNY TPNVGEYATF EAIRKAFRVW ESATPLRFRE VPYAYIREGH EKQADIMIFF
AEGFHGDSTP FDGEGGFLAH AYFPGPNIGG DTHFDSAEPW TVRNEDLNGN DIFLVAVHEL
GHALGLEHSN DPSAIMAPFY QWMDTENFVL PDDDRRGIQQ LYGSKSGSPT KMPPQPRTTS
RPSVPDKPKN PTYGPNICDG NFDTVAMLRG EMFVFKERWF WRVRKNQVMD GYPMPIGQFW
RGLPASINTA YERKDGKFVF FKGDKHWVFD EASLEPGYPK HIKELGRGLP TDRIDAALFW
MPNGKTYFFR GNKYYRFNEE LRIVESEYPK NIKVWEGIPE SPRGSFMGSD EVFTYFYKGN
KYWKFNNQKL KVEPGYPKSA LRDWMGCPSS GGQPDEGTEE ETEVIIIEVD EEGSGAVSAA
AVVLPVLLLL LVLAVGLAVF FFRRHGTPKR LLYCQRSLLD KV
