ID MMP2_BOVIN Reviewed; 661 AA.
AC Q9GLE5;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 24-JAN-2024, entry version 123.
DE RecName: Full=72 kDa type IV collagenase;
DE EC=3.4.24.24 {ECO:0000250|UniProtKB:P08253};
DE AltName: Full=72 kDa gelatinase;
DE AltName: Full=Matrix metalloproteinase-2;
DE Short=MMP-2;
DE Contains:
DE RecName: Full=PEX;
DE Flags: Precursor;
GN Name=MMP2;
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 Yan L., Zhang B., Tsang P., Fang J., Yu Y., Ingber D.E., Moses M.A.;
RT "Molecular cloning and biological characterization of bovine matrix
RT metalloprotease 2 (bMMP-2).";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Ubiquitinous metalloproteinase that is involved in diverse
CC functions such as remodeling of the vasculature, angiogenesis, tissue
CC repair, tumor invasion, inflammation, and atherosclerotic plaque
CC rupture. As well as degrading extracellular matrix proteins, can also
CC act on several nonmatrix proteins such as big endothelial 1 and beta-
CC type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu
CC bond. Appears to have a role in myocardial cell death pathways.
CC Contributes to myocardial oxidative stress by regulating the activity
CC of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of
CC the fibrovascular tissues (By similarity). {ECO:0000250}.
CC -!- FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, posseses
CC anti-angiogenic and anti-tumor properties and inhibits cell migration
CC and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-
CC v/beta-3 on the surface of blood vessels (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of gelatin type I and collagen types IV, V, VII, X.
CC Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.;
CC EC=3.4.24.24; Evidence={ECO:0000250|UniProtKB:P08253};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P08253};
CC Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000250|UniProtKB:P08253};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P08253};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P08253};
CC -!- SUBUNIT: Interacts (via the C-terminal hemopexin-like domains-
CC containing region) with the integrin alpha-V/beta-3; the interaction
CC promotes vascular invasion in angiogenic vessels and melamoma cells.
CC Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-
CC terminal); the interaction inhibits the degradation activity. Interacts
CC with GSK3B (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}. Membrane {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Colocalizes with integrin alphaV/beta3 at the membrane surface in
CC angiogenic blood vessels and melanomas. Found in mitochondria, along
CC microfibrils, and in nuclei of cardiomyocytes (By similarity).
CC {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: Phosphorylation on multiple sites modulates enzymatic activity.
CC Phosphorylated by PKC in vitro (By similarity). {ECO:0000250}.
CC -!- PTM: The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-
CC MMP3). Autocatalytic cleavage in the C-terminal produces the anti-
CC angiogenic peptide, PEX. This processing appears to be facilitated by
CC binding integrinv/beta3 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AF290428; AAG28169.1; -; mRNA.
DR RefSeq; NP_777170.1; NM_174745.2.
DR AlphaFoldDB; Q9GLE5; -.
DR SMR; Q9GLE5; -.
DR STRING; 9913.ENSBTAP00000025657; -.
DR MEROPS; M10.003; -.
DR GlyCosmos; Q9GLE5; 2 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000025657; -.
DR GeneID; 282872; -.
DR KEGG; bta:282872; -.
DR CTD; 4313; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; Q9GLE5; -.
DR OrthoDB; 5340816at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0071492; P:cellular response to UV-A; ISS:UniProtKB.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0048771; P:tissue remodeling; IBA:GO_Central.
DR CDD; cd00062; FN2; 3.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 2.
DR Gene3D; 2.10.10.10; Fibronectin, type II, collagen-binding; 2.
DR Gene3D; 2.110.10.10; Hemopexin-like domain; 1.
DR InterPro; IPR000562; FN_type2_dom.
DR InterPro; IPR036943; FN_type2_sf.
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; IPR013806; Kringle-like.
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; IPR021158; Pept_M10A_Zn_BS.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR PANTHER; PTHR10201:SF29; 72 KDA TYPE IV COLLAGENASE; 1.
DR PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1.
DR Pfam; PF00040; fn2; 3.
DR Pfam; PF00045; Hemopexin; 4.
DR Pfam; PF00413; Peptidase_M10; 2.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00013; FNTYPEII.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00059; FN2; 3.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF50923; Hemopexin-like domain; 1.
DR SUPFAM; SSF57440; Kringle-like; 3.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR SUPFAM; SSF47090; PGBD-like; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS00023; FN2_1; 3.
DR PROSITE; PS51092; FN2_2; 3.
DR PROSITE; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Angiogenesis; Calcium; Collagen degradation; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..30
FT /evidence="ECO:0000250|UniProtKB:P33436"
FT PROPEP 31..110
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000244644"
FT CHAIN 111..661
FT /note="72 kDa type IV collagenase"
FT /id="PRO_0000244645"
FT CHAIN 446..661
FT /note="PEX"
FT /evidence="ECO:0000250"
FT /id="PRO_0000391625"
FT DOMAIN 229..277
FT /note="Fibronectin type-II 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 287..335
FT /note="Fibronectin type-II 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 345..393
FT /note="Fibronectin type-II 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT REPEAT 469..517
FT /note="Hemopexin 1"
FT REPEAT 518..564
FT /note="Hemopexin 2"
FT REPEAT 566..614
FT /note="Hemopexin 3"
FT REPEAT 615..661
FT /note="Hemopexin 4"
FT REGION 111..222
FT /note="Collagenase-like 1"
FT REGION 223..397
FT /note="Collagen-binding"
FT REGION 398..466
FT /note="Collagenase-like 2"
FT REGION 415..661
FT /note="Required for inhibitor TIMP2 binding"
FT /evidence="ECO:0000250"
FT MOTIF 101..108
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 135
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 205
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 404
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 477
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 522
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 570
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 619
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT CARBOHYD 574
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 234..260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 248..275
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 292..318
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 306..333
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 350..376
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 364..391
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 470..661
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
SQ SEQUENCE 661 AA; 73777 MW; 90545F7645E5F84D CRC64;
MTEARVSRGA LAALLRALCA LGCLLGRAAA APSPIIKFPG DVAPKTDKEL AVQYLNTFYG
CPKESCNLFV LKDTLKKMQK FFGLPQTGEL DQSTIETMRK PRCGNPDVAN YNFFPRKPKW
DKNQITYRII GYTPDLDPQT VDDAFARAFQ VWSDVTPLRF SRIHDGEADI MINFGRWEHG
DGYPFDGKDG LLAHAFAPGP GVGGDSHFDD DELRTLGEGQ VVRVKYGNAD GEYCKFPFRF
NGKEYTSCTD TGRSDGFLWC STTYNFDKDG KYGFCPHEAL FTMGGNADGQ PCKFPFRFQG
TSYDSCTTEG RTDGYRWCGT TEDYDRDKEY GFCPETAMST VGGNSEGAPC VLPFTFLGNK
HESCTSAGRS DGKLWCATTS NYDDDRKWGF CPDQGYSLFL VAAHEFGHAM GLEHSQDPGA
LMAPIYTYTK NFRLSHDDIQ GIQELYGASP DIDTGTGPTP TLGPVTPELC KQDIVFDGIS
QIRGEIFFFK DRFIWRTVTP RDKPTGPLLV ATFWPELPEK IDAVYEDPQE EKAVFFAGNE
YWVYSASTLE RGYPKPLTSL GLPPGVQKVD AAFNWSKNKK TYIFAGDKFW RYNEVKKKMD
PGFPKLIADA WNAIPDNLDA VVDLQGGGHS YFFKGAYYLK LENQSLKSVK FGSIKSDWLG
C
//
