ID   MMP8_MOUSE              Reviewed;         465 AA.
AC   O70138; O88733; Q6GTR5;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 184.
DE   RecName: Full=Neutrophil collagenase;
DE            EC=3.4.24.34;
DE   AltName: Full=Collagenase 2;
DE   AltName: Full=Matrix metalloproteinase-8;
DE            Short=MMP-8;
DE   Flags: Precursor;
GN   Name=Mmp8;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9516153;
RA   Lawson N.D., Khanna-Gupta A., Berliner N.;
RT   "Isolation and characterization of the cDNA for mouse neutrophil
RT   collagenase: demonstration of shared negative regulatory pathways for
RT   neutrophil secondary granule protein gene expression.";
RL   Blood 91:2517-2524(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=129/Sv; TISSUE=Embryo;
RX   PubMed=9727011; DOI=10.1074/jbc.273.37.23959;
RA   Balbin M., Fueyo A., Knaeuper V., Pendas A.M., Lopez J.M., Jimenez M.G.,
RA   Murphy G., Lopez-Otin C.;
RT   "Collagenase 2 (MMP-8) expression in murine tissue-remodelling processes.
RT   Analysis of its potential role in postpartum involution of the uterus.";
RL   J. Biol. Chem. 273:23959-23968(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Bone, and Dendritic cell;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=129; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Can degrade fibrillar type I, II, and III collagens. May play
CC       a role in the degradation of collagen fibers during uterine involution.
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. Activated by matrilysin.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Secreted, extracellular
CC       space, extracellular matrix. Note=Stored in intracellular granules and
CC       released during inflammatory conditions.
CC   -!- TISSUE SPECIFICITY: Neutrophils. Expressed in uterus. Low levels in
CC       kidney and muscle.
CC   -!- DEVELOPMENTAL STAGE: Expressed in late embryogenesis and in the
CC       involuting postpartum uterus.
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; U96696; AAC12707.1; -; mRNA.
DR   EMBL; Y13342; CAA73786.1; -; mRNA.
DR   EMBL; AK089234; BAC40805.1; -; mRNA.
DR   EMBL; AK137468; BAE23365.1; -; mRNA.
DR   EMBL; AK154937; BAE32938.1; -; mRNA.
DR   EMBL; CH466522; EDL24937.1; -; Genomic_DNA.
DR   EMBL; BC042742; AAH42742.1; -; mRNA.
DR   CCDS; CCDS22808.1; -.
DR   RefSeq; NP_032637.3; NM_008611.4.
DR   AlphaFoldDB; O70138; -.
DR   SMR; O70138; -.
DR   STRING; 10090.ENSMUSP00000018765; -.
DR   MEROPS; M10.002; -.
DR   GlyCosmos; O70138; 2 sites, No reported glycans.
DR   GlyGen; O70138; 3 sites, 1 O-linked glycan (1 site).
DR   PhosphoSitePlus; O70138; -.
DR   MaxQB; O70138; -.
DR   PaxDb; 10090-ENSMUSP00000018765; -.
DR   ProteomicsDB; 295695; -.
DR   Antibodypedia; 18018; 710 antibodies from 40 providers.
DR   DNASU; 17394; -.
DR   Ensembl; ENSMUST00000018765.4; ENSMUSP00000018765.3; ENSMUSG00000005800.4.
DR   GeneID; 17394; -.
DR   KEGG; mmu:17394; -.
DR   UCSC; uc009ocr.2; mouse.
DR   AGR; MGI:1202395; -.
DR   CTD; 4317; -.
DR   MGI; MGI:1202395; Mmp8.
DR   VEuPathDB; HostDB:ENSMUSG00000005800; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   GeneTree; ENSGT00940000161871; -.
DR   HOGENOM; CLU_015489_6_0_1; -.
DR   InParanoid; O70138; -.
DR   OMA; SNLWLNC; -.
DR   OrthoDB; 391167at2759; -.
DR   PhylomeDB; O70138; -.
DR   TreeFam; TF315428; -.
DR   BRENDA; 3.4.24.34; 3474.
DR   Reactome; R-MMU-1442490; Collagen degradation.
DR   Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   BioGRID-ORCS; 17394; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Mmp8; mouse.
DR   PRO; PR:O70138; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; O70138; Protein.
DR   Bgee; ENSMUSG00000005800; Expressed in granulocyte and 75 other cell types or tissues.
DR   GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR   GO; GO:0004175; F:endopeptidase activity; IMP:ARUK-UCL.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; ISO:MGI.
DR   GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0043120; F:tumor necrosis factor binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:ARUK-UCL.
DR   GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR   GO; GO:0035987; P:endodermal cell differentiation; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:1903980; P:positive regulation of microglial cell activation; IMP:ARUK-UCL.
DR   GO; GO:0150078; P:positive regulation of neuroinflammatory response; IMP:ARUK-UCL.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR   GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:ARUK-UCL.
DR   GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   CDD; cd00094; HX; 1.
DR   CDD; cd04278; ZnMc_MMP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.110.10.10; Hemopexin-like domain; 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; 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; MATRIX METALLOPROTEINASE; 1.
DR   PANTHER; PTHR10201:SF137; NEUTROPHIL COLLAGENASE; 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; SSF50923; Hemopexin-like domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF47090; PGBD-like; 1.
DR   PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR   PROSITE; PS00024; HEMOPEXIN; 1.
DR   PROSITE; PS51642; HEMOPEXIN_2; 4.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; O70138; MM.
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..100
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028746"
FT   CHAIN           101..465
FT                   /note="Neutrophil collagenase"
FT                   /id="PRO_0000028747"
FT   REPEAT          276..325
FT                   /note="Hemopexin 1"
FT   REPEAT          326..372
FT                   /note="Hemopexin 2"
FT   REPEAT          374..420
FT                   /note="Hemopexin 3"
FT   REPEAT          421..464
FT                   /note="Hemopexin 4"
FT   MOTIF           89..96
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        218
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         91
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         157
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         167
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         174
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
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         177
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         179
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         189
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         191
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         193
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         195
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         197
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         200
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         217
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         221
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         227
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         286
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         378
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         425
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        55
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        112
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        279..464
FT                   /evidence="ECO:0000250"
FT   CONFLICT        116
FT                   /note="R -> W (in Ref. 1; AAC12707)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        300
FT                   /note="D -> E (in Ref. 1; AAC12707)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        324
FT                   /note="F -> G (in Ref. 1; AAC12707)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        401
FT                   /note="Q -> E (in Ref. 1; AAC12707)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   465 AA;  53126 MW;  448AEC59639E9237 CRC64;
     MFRLKTLPLL IFLHTQLANA FPVPEHLEEK NIKTAENYLR KFYNLPSNQF RSSRNATMVA
     EKLKEMQRFF SLAETGKLDA ATMGIMEMPR CGVPDSGDFL LTPGSPKWTH TNLTYRIINH
     TPQLSRAEVK TAIEKAFHVW SVASPLTFTE ILQGEADINI AFVSRDHGDN SPFDGPNGIL
     AHAFQPGQGI GGDAHFDSEE TWTQDSKNYN LFLVAAHEFG HSLGLSHSTD PGALMYPNYA
     YREPSTYSLP QDDINGIQTI YGPSDNPIQP TGPSTPKACD PHLRFDATTT LRGEIYFFKD
     KYFWRRHPQL RTVDLNFISL FWPFLPNGLQ AAYEDFDRDL VFLFKGRQYW ALSGYDLQQG
     YPRDISNYGF PRSVQAIDAA VSYNGKTYFF INNQCWRYDN QRRSMDPGYP KSIPSMFPGV
     NCRVDAVFLQ DSFFLFFSGP QYFAFNFVSH RVTRVARSNL WLNCS
//