MMP9_RABIT
ID MMP9_RABIT Reviewed; 707 AA.
AC P41246;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Matrix metalloproteinase-9 {ECO:0000303|PubMed:8195136};
DE Short=MMP-9 {ECO:0000303|PubMed:8195136};
DE EC=3.4.24.35 {ECO:0000250|UniProtKB:P14780};
DE AltName: Full=92 kDa gelatinase;
DE AltName: Full=92 kDa type IV collagenase;
DE AltName: Full=Gelatinase B;
DE Short=GELB;
DE Flags: Precursor;
GN Name=MMP9 {ECO:0000303|PubMed:8195136};
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=Bone;
RX PubMed=8195136; DOI=10.1016/s0021-9258(17)36566-3;
RA Tezuka K.I., Nemoto K., Tezuka Y., Sato T., Ikeda Y., Kobori M.,
RA Kawashima H., Eguchi H., Hakeda Y., Kumegawa M.;
RT "Identification of matrix metalloproteinase 9 in rabbit osteoclasts.";
RL J. Biol. Chem. 269:15006-15009(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-171.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=7961810; DOI=10.1016/s0021-9258(19)61950-2;
RA Fini M.E., Bartlett J.D., Matsubara M., Rinehart W.B., Mody M.K.,
RA Girard M.T., Rainville M.;
RT "The rabbit gene for 92-kDa matrix metalloproteinase. Role of AP1 and AP2
RT in cell type-specific transcription.";
RL J. Biol. Chem. 269:28620-28628(1994).
CC -!- FUNCTION: Matrix metalloproteinase that plays an essential role in
CC local proteolysis of the extracellular matrix and in leukocyte
CC migration (By similarity). Could play a role in bone osteoclastic
CC resorption (By similarity). Cleaves KiSS1 at a Gly-|-Leu bond (By
CC similarity). Cleaves NINJ1 to generate the Secreted ninjurin-1 form (By
CC similarity). Cleaves type IV and type V collagen into large C-terminal
CC three quarter fragments and shorter N-terminal one quarter fragments.
CC Degrades fibronectin but not laminin or Pz-peptide (By similarity).
CC {ECO:0000250|UniProtKB:P14780, ECO:0000250|UniProtKB:P41245}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of gelatin types I and V and collagen types IV and
CC V.; EC=3.4.24.35; Evidence={ECO:0000250|UniProtKB:P14780};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P14780};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P14780};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P14780};
CC Note=Binds 3 Ca(2+) ions per subunit. {ECO:0000250|UniProtKB:P14780};
CC -!- SUBUNIT: Exists as monomer or homodimer; disulfide-linked. Exists also
CC as heterodimer with LCN2. Macrophages and transformed cell lines
CC produce only the monomeric form. Interacts with ECM1.
CC {ECO:0000250|UniProtKB:P14780}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:P14780}.
CC -!- TISSUE SPECIFICITY: Osteoclasts. {ECO:0000269|PubMed:8195136}.
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. {ECO:0000250|UniProtKB:P14780}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P14780}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; D26514; BAA05520.1; -; mRNA.
DR EMBL; L36050; AAA64358.1; -; Genomic_DNA.
DR PIR; A53796; A53796.
DR RefSeq; NP_001075672.1; NM_001082203.1.
DR AlphaFoldDB; P41246; -.
DR SMR; P41246; -.
DR STRING; 9986.ENSOCUP00000025066; -.
DR MEROPS; M10.004; -.
DR GeneID; 100008993; -.
DR KEGG; ocu:100008993; -.
DR CTD; 4318; -.
DR eggNOG; KOG1565; Eukaryota.
DR InParanoid; P41246; -.
DR OrthoDB; 1075463at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032502; P:developmental process; IEA:UniProt.
DR GO; GO:0050900; P:leukocyte migration; IEA:InterPro.
DR GO; GO:0001503; P:ossification; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProt.
DR CDD; cd00062; FN2; 3.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.10.10.10; -; 3.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 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; IPR028688; MMP9.
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; IPR036365; PGBD-like_sf.
DR InterPro; IPR006970; PT.
DR PANTHER; PTHR10201:SF30; PTHR10201:SF30; 1.
DR Pfam; PF00040; fn2; 3.
DR Pfam; PF00045; Hemopexin; 3.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF04886; PT; 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 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..19
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT PROPEP 20..106
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT /id="PRO_0000028760"
FT CHAIN 107..707
FT /note="Matrix metalloproteinase-9"
FT /id="PRO_0000028761"
FT DOMAIN 225..273
FT /note="Fibronectin type-II 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 283..331
FT /note="Fibronectin type-II 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DOMAIN 342..390
FT /note="Fibronectin type-II 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT REPEAT 518..563
FT /note="Hemopexin 1"
FT REPEAT 564..608
FT /note="Hemopexin 2"
FT REPEAT 610..657
FT /note="Hemopexin 3"
FT REPEAT 658..704
FT /note="Hemopexin 4"
FT REGION 437..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 97..104
FT /note="Cysteine switch"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT COMPBIAS 445..471
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 402
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 99
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|UniProtKB:P14780"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 182
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 190
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 205
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 401
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 405
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT BINDING 411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14780"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 230..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 244..271
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 288..314
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 302..329
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 347..373
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 361..388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT DISULFID 516..704
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00479"
FT CONFLICT 76
FT /note="K -> P (in Ref. 2; AAA64358)"
FT /evidence="ECO:0000305"
FT CONFLICT 100..102
FT /note="GVP -> ASR (in Ref. 2; AAA64358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 707 AA; 78308 MW; 053BCE8DC4D4758F CRC64;
MSPRQPLVLA LLVLGCCSAA PRRRQPTLVV FPGELRTRLT DRQLAEEYLF RYGYTRVASM
HGDSQSLRLP LLLLQKHLSL PETGELDNAT LEAMRAPRCG VPDVGKFQTF EGDLKWHHHN
ITYWIQNYSE DLPRDVIDDA FARAFALWSA VTPLTFTRVY SRDADIVIQF GVAEHGDGYP
FDGKDGLLAH AFPPGPGIQG DAHFDDEELW SLGKGVVVPT YFGNADGAPC HFPFTFEGRS
YTACTTDGRS DGMAWCSTTA DYDTDRRFGF CPSERLYTQD GNADGKPCEF PFIFQGRTYS
ACTTDGRSDG HRWCATTASY DKDKLYGFCP TRADSTVVGG NSAGELCVFP FVFLGKEYSS
CTSEGRRDGR LWCATTSNFD SDKKWGFCPD KGYSLFLVAA HEFGHALGLD HSSVPERLMY
PMYRYLEGSP LHEDDVRGIQ HLYGPNPNPQ PPATTTPEPQ PTAPPTACPT WPATVRPSEH
PTTSPTGAPS AGPTGPPTAS PSAAPTASLD PAEDVCNVNV FDAIAEIGNK LHVFKDGRYW
RFSEGSGRRP QGPFLIADTW PALPAKLDSA FEEPLTKKLF FFSGRQVWVY TGASVLGPRR
LDKLGLGPEV PHVTGALPRA GGKVLLFGAQ RFWRFDVKTQ TVDSRSGAPV DQMFPGVPLN
THDVFQYREK AYFCQDRFFW RVSTRNEVNL VDQVGYVSFD ILHCPED