MMP14_RABIT
ID MMP14_RABIT Reviewed; 582 AA.
AC Q95220; P79225;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 143.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Vascular smooth muscle;
RA Wang H., Keiser J.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-572.
RC STRAIN=New Zealand white;
RA Sato T.;
RL Submitted (OCT-1996) 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: 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; U83918; AAB41500.1; -; mRNA.
DR EMBL; U73940; AAD13803.1; -; Genomic_DNA.
DR RefSeq; NP_001076262.1; NM_001082793.1.
DR AlphaFoldDB; Q95220; -.
DR BMRB; Q95220; -.
DR SMR; Q95220; -.
DR STRING; 9986.ENSOCUP00000008835; -.
DR MEROPS; M10.014; -.
DR GeneID; 100009598; -.
DR KEGG; ocu:100009598; -.
DR CTD; 4323; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; Q95220; -.
DR OrthoDB; 1075463at2759; -.
DR Proteomes; UP000001811; 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: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: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 InterPro; IPR006311; TAT_signal.
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_0000028804"
FT CHAIN 112..582
FT /note="Matrix metalloproteinase-14"
FT /id="PRO_0000028805"
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 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 29
FT /note="Q -> K (in Ref. 2; AAD13803)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="K -> N (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="L -> V (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="E -> D (in Ref. 2; AAD13803)"
FT /evidence="ECO:0000305"
FT CONFLICT 292..296
FT /note="RCLLN -> KMPPP (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 298..300
FT /note="GQP -> RTT (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 302..308
FT /note="GLLFRIS -> RTFIPDK (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="G -> R (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="K -> N (in Ref. 2; AAD13803)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="F -> L (in Ref. 2; AAD13803)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="L -> F (in Ref. 2; AAD13803)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 582 AA; 65963 MW; 844624B0AF1B6812 CRC64;
MSPAPRPSRR LLLPLLTLGT ALASLGSAQS NSFSPEAWLQ QYGYLPPGDL RTHTQRSPQS
LSAAIAAMQR FYGLRVTGKA DTDTMKAMRR PRCGVPDKFG AEIKANVRRK RYAIQGLKWQ
HNEITFCIQN YTPKVGEYAT FEAIRKAFRV WESATPLRFR EVHYAYIRDG REKQADIMIF
FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVRNEDLNG NDIFLVAVHE
LGHALGLEHS NDPSAIMAPF YQWMDTEKFL LPDDERRGIQ QLYGSQSGSP TRCLLNPGQP
SGLLFRISPG NPTYGPKICD GNFDTVAVFR GEMFVFKERW FWRVRNNQVM DGYPMPIGQL
WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF
WMPNGKTYFF RGNKYYRFNE ELRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG
NKYWKFNNQK LKVEPGYPKS ALRDWMGCPA GGRPDEGTEE ETEVIIIEVD EEGSGAVSAA
AVVLPVLLLL LVLAVGLAVF FFRRHGTPKR LLYCQRSLLD KV
