MMP8_MOUSE
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 03-AUG-2022, entry version 176.
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 GlyGen; O70138; 2 sites.
DR PhosphoSitePlus; O70138; -.
DR MaxQB; O70138; -.
DR PaxDb; O70138; -.
DR PRIDE; O70138; -.
DR ProteomicsDB; 295695; -.
DR Antibodypedia; 18018; 679 antibodies from 40 providers.
DR DNASU; 17394; -.
DR Ensembl; ENSMUST00000018765; ENSMUSP00000018765; ENSMUSG00000005800.
DR GeneID; 17394; -.
DR KEGG; mmu:17394; -.
DR UCSC; uc009ocr.2; mouse.
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; 1075463at2759; -.
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 73 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 tissues.
DR Genevisible; O70138; MM.
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; ISO:MGI.
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:0008270; F:zinc ion binding; ISO:MGI.
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:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:ARUK-UCL.
DR GO; GO:0043388; P:positive regulation of DNA binding; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:ARUK-UCL.
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:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:ARUK-UCL.
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; IMP:ARUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; 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; 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; 3.
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..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
