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   24-JAN-2024, entry version 157.
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   GlyCosmos; P41246; 3 sites, No reported glycans.
DR   PaxDb; 9986-ENSOCUP00000025066; -.
DR   GeneID; 100008993; -.
DR   KEGG; ocu:100008993; -.
DR   CTD; 4318; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   InParanoid; P41246; -.
DR   OrthoDB; 5340816at2759; -.
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:0048856; P:anatomical structure development; IEA:UniProt.
DR   GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
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; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.10.10.10; Fibronectin, type II, collagen-binding; 3.
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; IPR036365; PGBD-like_sf.
DR   InterPro; IPR006970; PT.
DR   PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1.
DR   PANTHER; PTHR10201:SF30; MATRIX METALLOPROTEINASE-9; 1.
DR   Pfam; PF00040; fn2; 3.
DR   Pfam; PF00045; Hemopexin; 3.
DR   Pfam; PF00413; Peptidase_M10; 2.
DR   Pfam; PF04886; PT; 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   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
//