MMP14_PIG
ID MMP14_PIG Reviewed; 580 AA.
AC Q9XT90;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 145.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9881602; DOI=10.1016/s0945-053x(98)90098-1;
RA Caron C., Xue J., Bartlett J.D.;
RT "Expression and localization of membrane type 1 matrix metalloproteinase in
RT tooth tissues.";
RL Matrix Biol. 17:501-511(1998).
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 -!- TISSUE SPECIFICITY: Highly expressed in developing tooth tissues.
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; AF067419; AAD38324.1; -; mRNA.
DR RefSeq; NP_999404.1; NM_214239.1.
DR AlphaFoldDB; Q9XT90; -.
DR SMR; Q9XT90; -.
DR STRING; 9823.ENSSSCP00000002229; -.
DR MEROPS; M10.014; -.
DR PaxDb; Q9XT90; -.
DR GeneID; 397471; -.
DR KEGG; ssc:397471; -.
DR CTD; 4323; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; Q9XT90; -.
DR OrthoDB; 1075463at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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..28
FT /evidence="ECO:0000255"
FT PROPEP 29..109
FT /note="Activation peptide"
FT /id="PRO_0000028802"
FT CHAIN 110..580
FT /note="Matrix metalloproteinase-14"
FT /id="PRO_0000028803"
FT TOPO_DOM 110..539
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 540..560
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 561..580
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 314..362
FT /note="Hemopexin 1"
FT REPEAT 363..408
FT /note="Hemopexin 2"
FT REPEAT 410..458
FT /note="Hemopexin 3"
FT REPEAT 459..506
FT /note="Hemopexin 4"
FT REGION 282..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 89..96
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 91
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 237
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT MOD_RES 397
FT /note="Phosphotyrosine; by PKDCC"
FT /evidence="ECO:0000250|UniProtKB:P50281"
FT DISULFID 317..506
FT /evidence="ECO:0000250"
SQ SEQUENCE 580 AA; 65934 MW; B7B2C2C569A96CAC CRC64;
MSPAPRPVRS LLLPLLTLAS ALASLSSAQS FSPEAWLQQY GYLPPGDLRT HTQRSPQSLS
AAIAAMQRFY GLRVTGKADA DTMKAMRRPR CGVPDKFGAE IKANVRRKRY AIQGLKWQHN
EITFCIQNYT PKVGEYATFE AIRKAFRVWE SATPLRFREV PYAYIREGHE KQADIMIFFA
EGFHGDSTPF DGEGGFLAHA YFPGPNIGGD THFDSAEPWT VRNEDLNGND IFLVAVHELG
HALGLEHSND PSAIMAPFYQ WMDTENFVLP DDDRRGIQQL YGSESGFPTK MPPQPRTTSK
PSVPDKPKNP TYGPNICDGN FDTVAMLRGE MFVFKERWFW RVRKNQVMDG YPMPIGQFWR
GLPASINTAY ERKDGKFVFF KGDKHWVFDE ASLEPGYPKH IKELGRRLPT DKIDAALFWM
PNGKDYFFRG NKYYRFNEEL RAVDSEYPKN IKVWEGIPES PRGSFMGSDE VFTYFYKGNK
YWKFNNQKLK VEPGYPKSAL RDWMGCPSGG RPDEGTEEET EVIIIEVDEE GSGAVSAAAV
VLPVLLLLLV LAVGLAVFFF RRHGTPKRLL YCQRSLLDKV
