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Protein

Neutrophil collagenase

Gene

Mmp8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Can degrade fibrillar type I, II, and III collagens. May play a role in the degradation of collagen fibers during uterine involution.

Catalytic activityi

Cleavage of interstitial collagens in the triple helical domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen more slowly than type I.

Cofactori

Protein has several cofactor binding sites:
  • Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit.By similarity
  • Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Enzyme regulationi

Cannot be activated without removal of the activation peptide. Activated by matrilysin.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi91 – 911Zinc 2; in inhibited formBy similarity
Metal bindingi157 – 1571Calcium 1By similarity
Metal bindingi167 – 1671Zinc 1By similarity
Metal bindingi169 – 1691Zinc 1By similarity
Metal bindingi174 – 1741Calcium 2By similarity
Metal bindingi175 – 1751Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi177 – 1771Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi179 – 1791Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi182 – 1821Zinc 1By similarity
Metal bindingi189 – 1891Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi191 – 1911Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi193 – 1931Calcium 1By similarity
Metal bindingi195 – 1951Zinc 1By similarity
Metal bindingi197 – 1971Calcium 2By similarity
Metal bindingi200 – 2001Calcium 2By similarity
Metal bindingi217 – 2171Zinc 2; catalyticBy similarity
Active sitei218 – 2181PROSITE-ProRule annotation
Metal bindingi221 – 2211Zinc 2; catalyticBy similarity
Metal bindingi227 – 2271Zinc 2; catalyticBy similarity
Metal bindingi286 – 2861Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi378 – 3781Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi425 – 4251Calcium 3; via carbonyl oxygenBy similarity

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. metalloendopeptidase activity Source: InterPro
  3. serine-type endopeptidase activity Source: UniProtKB
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. collagen catabolic process Source: UniProtKB-KW
  2. endodermal cell differentiation Source: Ensembl
  3. proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Collagen degradation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_313067. Collagen degradation.
REACT_332323. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil collagenase (EC:3.4.24.34)
Alternative name(s):
Collagenase 2
Matrix metalloproteinase-8
Short name:
MMP-8
Gene namesi
Name:Mmp8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1202395. Mmp8.

Subcellular locationi

Cytoplasmic granule. Secretedextracellular spaceextracellular matrix
Note: Stored in intracellular granules and released during inflammatory conditions.

GO - Cellular componenti

  1. extracellular space Source: UniProtKB
  2. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020By similarityAdd
BLAST
Propeptidei21 – 10080Activation peptidePRO_0000028746Add
BLAST
Chaini101 – 465365Neutrophil collagenasePRO_0000028747Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi55 – 551N-linked (GlcNAc...)Sequence Analysis
Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi279 ↔ 464By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PRIDEiO70138.

PTM databases

PhosphoSiteiO70138.

Expressioni

Tissue specificityi

Neutrophils. Expressed in uterus. Low levels in kidney and muscle.

Developmental stagei

Expressed in late embryogenesis and in the involuting postpartum uterus.

Gene expression databases

BgeeiO70138.
CleanExiMM_MMP8.
GenevestigatoriO70138.

Structurei

3D structure databases

ProteinModelPortaliO70138.
SMRiO70138. Positions 32-464.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati276 – 32550Hemopexin 1Add
BLAST
Repeati326 – 37247Hemopexin 2Add
BLAST
Repeati374 – 42047Hemopexin 3Add
BLAST
Repeati421 – 46444Hemopexin 4Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi89 – 968Cysteine switchBy similarity

Domaini

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG258253.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiO70138.
KOiK01402.
OMAiYAFREPS.
OrthoDBiEOG7XPZ57.
TreeFamiTF315428.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028709. MMP8.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF137. PTHR10201:SF137. 1 hit.
PfamiPF00045. Hemopexin. 3 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O70138-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFRLKTLPLL IFLHTQLANA FPVPEHLEEK NIKTAENYLR KFYNLPSNQF
60 70 80 90 100
RSSRNATMVA EKLKEMQRFF SLAETGKLDA ATMGIMEMPR CGVPDSGDFL
110 120 130 140 150
LTPGSPKWTH TNLTYRIINH TPQLSRAEVK TAIEKAFHVW SVASPLTFTE
160 170 180 190 200
ILQGEADINI AFVSRDHGDN SPFDGPNGIL AHAFQPGQGI GGDAHFDSEE
210 220 230 240 250
TWTQDSKNYN LFLVAAHEFG HSLGLSHSTD PGALMYPNYA YREPSTYSLP
260 270 280 290 300
QDDINGIQTI YGPSDNPIQP TGPSTPKACD PHLRFDATTT LRGEIYFFKD
310 320 330 340 350
KYFWRRHPQL RTVDLNFISL FWPFLPNGLQ AAYEDFDRDL VFLFKGRQYW
360 370 380 390 400
ALSGYDLQQG YPRDISNYGF PRSVQAIDAA VSYNGKTYFF INNQCWRYDN
410 420 430 440 450
QRRSMDPGYP KSIPSMFPGV NCRVDAVFLQ DSFFLFFSGP QYFAFNFVSH
460
RVTRVARSNL WLNCS
Length:465
Mass (Da):53,126
Last modified:July 27, 2011 - v2
Checksum:i448AEC59639E9237
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti116 – 1161R → W in AAC12707 (PubMed:9516153).Curated
Sequence conflicti300 – 3001D → E in AAC12707 (PubMed:9516153).Curated
Sequence conflicti324 – 3241F → G in AAC12707 (PubMed:9516153).Curated
Sequence conflicti401 – 4011Q → E in AAC12707 (PubMed:9516153).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96696 mRNA. Translation: AAC12707.1.
Y13342 mRNA. Translation: CAA73786.1.
AK089234 mRNA. Translation: BAC40805.1.
AK137468 mRNA. Translation: BAE23365.1.
AK154937 mRNA. Translation: BAE32938.1.
CH466522 Genomic DNA. Translation: EDL24937.1.
BC042742 mRNA. Translation: AAH42742.1.
CCDSiCCDS22808.1.
RefSeqiNP_032637.3. NM_008611.4.
UniGeneiMm.16415.

Genome annotation databases

EnsembliENSMUST00000018765; ENSMUSP00000018765; ENSMUSG00000005800.
GeneIDi17394.
KEGGimmu:17394.
UCSCiuc009ocr.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96696 mRNA. Translation: AAC12707.1.
Y13342 mRNA. Translation: CAA73786.1.
AK089234 mRNA. Translation: BAC40805.1.
AK137468 mRNA. Translation: BAE23365.1.
AK154937 mRNA. Translation: BAE32938.1.
CH466522 Genomic DNA. Translation: EDL24937.1.
BC042742 mRNA. Translation: AAH42742.1.
CCDSiCCDS22808.1.
RefSeqiNP_032637.3. NM_008611.4.
UniGeneiMm.16415.

3D structure databases

ProteinModelPortaliO70138.
SMRiO70138. Positions 32-464.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM10.002.

PTM databases

PhosphoSiteiO70138.

Proteomic databases

PRIDEiO70138.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000018765; ENSMUSP00000018765; ENSMUSG00000005800.
GeneIDi17394.
KEGGimmu:17394.
UCSCiuc009ocr.2. mouse.

Organism-specific databases

CTDi4317.
MGIiMGI:1202395. Mmp8.

Phylogenomic databases

eggNOGiNOG258253.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiO70138.
KOiK01402.
OMAiYAFREPS.
OrthoDBiEOG7XPZ57.
TreeFamiTF315428.

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_313067. Collagen degradation.
REACT_332323. Activation of Matrix Metalloproteinases.

Miscellaneous databases

ChiTaRSiMmp8. mouse.
NextBioi292028.
PROiO70138.
SOURCEiSearch...

Gene expression databases

BgeeiO70138.
CleanExiMM_MMP8.
GenevestigatoriO70138.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028709. MMP8.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF137. PTHR10201:SF137. 1 hit.
PfamiPF00045. Hemopexin. 3 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of the cDNA for mouse neutrophil collagenase: demonstration of shared negative regulatory pathways for neutrophil secondary granule protein gene expression."
    Lawson N.D., Khanna-Gupta A., Berliner N.
    Blood 91:2517-2524(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Collagenase 2 (MMP-8) expression in murine tissue-remodelling processes. Analysis of its potential role in postpartum involution of the uterus."
    Balbin M., Fueyo A., Knaeuper V., Pendas A.M., Lopez J.M., Jimenez M.G., Murphy G., Lopez-Otin C.
    J. Biol. Chem. 273:23959-23968(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: 129/Sv.
    Tissue: Embryo.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Bone and Dendritic cell.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: 129.
    Tissue: Mammary tumor.

Entry informationi

Entry nameiMMP8_MOUSE
AccessioniPrimary (citable) accession number: O70138
Secondary accession number(s): O88733, Q6GTR5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.