MMP2_RABIT
ID MMP2_RABIT Reviewed; 662 AA.
AC P50757;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
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=Gelatinase A;
DE AltName: Full=Matrix metalloproteinase-2;
DE Short=MMP-2;
DE Contains:
DE RecName: Full=PEX;
DE Flags: Precursor;
GN Name=MMP2;
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=Japanese white; TISSUE=Synovial cell;
RX PubMed=8679695; DOI=10.1016/0167-4781(96)00050-4;
RA Matsumoto S., Katoh M., Watanabe T., Masuho Y.;
RT "Molecular cloning of rabbit matrix metalloproteinase-2 and its broad
RT expression at several tissues.";
RL Biochim. Biophys. Acta 1307:137-139(1996).
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-MMP3)
CC (By similarity). Autocatalytic cleavage in the C-terminal produces the
CC anti-angiogenic peptide, PEX. This processing appears to be facilitated
CC by binding integrinv/beta3 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; D63579; BAA09796.1; -; mRNA.
DR PIR; S70365; S70365.
DR RefSeq; NP_001075678.1; NM_001082209.1.
DR AlphaFoldDB; P50757; -.
DR SMR; P50757; -.
DR STRING; 9986.ENSOCUP00000005803; -.
DR MEROPS; M10.003; -.
DR PRIDE; P50757; -.
DR GeneID; 100009000; -.
DR KEGG; ocu:100009000; -.
DR CTD; 4313; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; P50757; -.
DR OrthoDB; 1075463at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
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; IEA:UniProtKB-EC.
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; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00062; FN2; 3.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.10.10.10; -; 2.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 2.
DR InterPro; IPR028708; 72kDa_collagenase.
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; PTHR10201:SF29; 1.
DR Pfam; PF00040; fn2; 3.
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; SM00059; FN2; 3.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR SUPFAM; SSF57440; SSF57440; 3.
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; Autocatalytic cleavage; Calcium; Collagen degradation;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..29
FT /evidence="ECO:0000250|UniProtKB:P33436"
FT PROPEP 30..109
FT /note="Activation peptide"
FT /id="PRO_0000028718"
FT CHAIN 110..662
FT /note="72 kDa type IV collagenase"
FT /id="PRO_0000028719"
FT CHAIN 445..662
FT /note="PEX"
FT /evidence="ECO:0000250"
FT /id="PRO_0000391628"
FT DOMAIN 228..276
FT /note="Fibronectin type-II 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 286..334
FT /note="Fibronectin type-II 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 344..392
FT /note="Fibronectin type-II 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT REPEAT 474..518
FT /note="Hemopexin 1"
FT REPEAT 519..565
FT /note="Hemopexin 2"
FT REPEAT 567..615
FT /note="Hemopexin 3"
FT REPEAT 616..662
FT /note="Hemopexin 4"
FT REGION 110..221
FT /note="Collagenase-like 1"
FT REGION 222..396
FT /note="Collagen-binding"
FT REGION 397..467
FT /note="Collagenase-like 2"
FT REGION 414..662
FT /note="Required for inhibitor TIMP2 binding"
FT /evidence="ECO:0000250"
FT MOTIF 100..107
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 102
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 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 211
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 211
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 403
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 407
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 413
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 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 523
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 571
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT BINDING 620
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P08253"
FT CARBOHYD 575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 644
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 233..259
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 247..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 291..317
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 305..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 349..375
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 363..390
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 471..662
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
SQ SEQUENCE 662 AA; 73803 MW; 1CC246B270E440C8 CRC64;
MEALGARGAL AGFLRALCVL GCLLGRATAP PSPVIKFPGD VAPKTDKELA VQYLNTFYGC
PKDSCNLFVL KDTLKKMQKF FGLPQTGELD QSTIETMRKP RCGNPDVANY NFFPRKPKWD
KNQITYRIIG YTPDLDPETV DDAFARAFQV WSNVTPLRFS RIHDGEADIM INFGRWEHGD
GYPFDGKDGL LAHAFAPGTG VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN
GKEYTSCTDT GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNADGQP CKFPFRFQGT
SYSSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTI GGNSEGAPCV FPFTFLGNKY
ESCTSAGRSD GKMWCATSTN YDDDRKWGFC PDQGYSLFLV AAHEFGHAMG LEHSQDPGAL
MAPIYTYTKN FRLSQDDIKG IQELYGASPD AGTDAGTGPT PTLGPVTPEI CTQDIVFDGI
AQIRGEIFFF KDRFIWRTVT PGDKPMGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN
EYWVYSASTL ERGYPKPLTS LGLPPDVQRV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM
DPGFPRLIAD AWNAIPDHLD AVVDLQGSGH SYFFKGTYYL KLENQSLKSV KVGSIKTDWL
GC
