MMP8_RAT
ID MMP8_RAT Reviewed; 466 AA.
AC O88766;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Neutrophil collagenase;
DE EC=3.4.24.34;
DE AltName: Full=Matrix metalloproteinase-8;
DE Short=MMP-8;
DE Flags: Precursor;
GN Name=Mmp8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Lewis;
RA Overall C.M., Lowne D., Wells G., Burel S., Clements J.M.;
RT "Cloning, expression, characterization and activation properties of rat
RT neutrophil collagenase (MMP-8).";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Can degrade fibrillar type I, II, and III collagens.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of interstitial collagens in the triple helical
CC domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen
CC more slowly than type I.; EC=3.4.24.34;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 3 Ca(2+) ions per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Cannot be activated without removal of the
CC activation peptide. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Secreted, extracellular
CC space, extracellular matrix {ECO:0000250}. Note=Stored in intracellular
CC granules.
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 -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AJ007288; CAA07432.1; -; mRNA.
DR RefSeq; NP_071557.1; NM_022221.1.
DR AlphaFoldDB; O88766; -.
DR SMR; O88766; -.
DR STRING; 10116.ENSRNOP00000013936; -.
DR BindingDB; O88766; -.
DR ChEMBL; CHEMBL2312; -.
DR MEROPS; M10.002; -.
DR GlyGen; O88766; 2 sites.
DR PaxDb; O88766; -.
DR PRIDE; O88766; -.
DR GeneID; 63849; -.
DR KEGG; rno:63849; -.
DR UCSC; RGD:631408; rat.
DR CTD; 4317; -.
DR RGD; 631408; Mmp8.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; O88766; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; O88766; -.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:O88766; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IMP:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IMP:RGD.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0035987; P:endodermal cell differentiation; ISO:RGD.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0001503; P:ossification; IEP:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:1903980; P:positive regulation of microglial cell activation; ISO:RGD.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; IMP:ARUK-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 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; IPR028709; MMP8.
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:SF137; PTHR10201:SF137; 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; Collagen degradation; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT PROPEP 21..101
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028748"
FT CHAIN 102..466
FT /note="Neutrophil collagenase"
FT /id="PRO_0000028749"
FT REPEAT 277..326
FT /note="Hemopexin 1"
FT REPEAT 327..373
FT /note="Hemopexin 2"
FT REPEAT 375..421
FT /note="Hemopexin 3"
FT REPEAT 422..465
FT /note="Hemopexin 4"
FT MOTIF 90..97
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 158
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 196
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 379
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 280..465
FT /evidence="ECO:0000305"
SQ SEQUENCE 466 AA; 53277 MW; 8B9DE97576E76C90 CRC64;
MLHLKTLPFL FFFHTQLATA LPVPPEHLEE KNMKTAENYL RKFYHLPSNQ FRSARNATMI
AEKLKEMQRF FGLPETGKPD AATIEIMEKP RCGVPDSGDF LLTPGSPKWT HTNLTYRIIN
HTPQMSKAEV KTEIEKAFKI WSVPSTLTFT ETLEGEADIN IAFVSRDHGD NSPFDGPNGI
LAHAFQPGRG IGGDAHFDSE ETWTQDSKNY NLFLVAAHEF GHSLGLSHST DPGALMYPNY
AYREPSTYSL PQDDINGIQT IYGPSDNPVQ PTGPSTPTAC DPHLRFDAAT TLRGEIYFFK
DKYFWRRHPQ LRTVDLNFIS LFWPFLPNGL QAAYEDFDRD LVFLFKGRQY WALSAYDLQQ
GYPRDISNYG FPRSVQAIDA AVSYNGKTYF FVNNQCWRYD NQRRSMDPGY PTSIASVFPG
INCRIDAVFQ QDSFFLFFSG PQYFAFNLVS RRVTRVARSN LWLNCP
