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Protein

Neutrophil collagenase

Gene

MMP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Can degrade fibrillar type I, II, and III collagens.

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+Note: Binds 3 Ca2+ ions per subunit.
  • Zn2+Note: Binds 2 Zn2+ ions per subunit.

Enzyme regulationi

Cannot be activated without removal of the activation peptide.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi91Zinc 2; in inhibited form1
Metal bindingi157Calcium 11
Metal bindingi167Zinc 11 Publication1
Metal bindingi169Zinc 11 Publication1
Metal bindingi174Calcium 21 Publication1
Metal bindingi175Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi177Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi179Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi182Zinc 11 Publication1
Metal bindingi189Calcium 1; via carbonyl oxygen1
Metal bindingi191Calcium 1; via carbonyl oxygen1
Metal bindingi193Calcium 11
Metal bindingi195Zinc 11 Publication1
Metal bindingi197Calcium 21 Publication1
Metal bindingi200Calcium 21 Publication1
Metal bindingi217Zinc 2; catalytic1 Publication1
Active sitei2181
Metal bindingi221Zinc 2; catalytic1 Publication1
Metal bindingi227Zinc 2; catalytic1 Publication1
Metal bindingi286Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi378Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi425Calcium 3; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • metalloendopeptidase activity Source: InterPro
  • serine-type endopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • collagen catabolic process Source: Reactome
  • endodermal cell differentiation Source: UniProtKB
  • extracellular matrix disassembly Source: Reactome
  • 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

BioCyciZFISH:HS04191-MONOMER.
BRENDAi3.4.24.34. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiM10.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil collagenase (EC:3.4.24.34)
Alternative name(s):
Matrix metalloproteinase-8
Short name:
MMP-8
PMNL collagenase
Short name:
PMNL-CL
Gene namesi
Name:MMP8
Synonyms:CLG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:7175. MMP8.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4317.
MalaCardsiMMP8.
OpenTargetsiENSG00000118113.
PharmGKBiPA30888.

Chemistry databases

ChEMBLiCHEMBL4588.
DrugBankiDB00786. Marimastat.
GuidetoPHARMACOLOGYi1632.

Polymorphism and mutation databases

BioMutaiMMP8.
DMDMi116862.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 202 PublicationsAdd BLAST20
PropeptideiPRO_000002874421 – 100Activation peptideAdd BLAST80
ChainiPRO_0000028745101 – 467Neutrophil collagenaseAdd BLAST367

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi54N-linked (GlcNAc...)Curated1
Glycosylationi73N-linked (GlcNAc...)Curated1
Glycosylationi112N-linked (GlcNAc...)1
Glycosylationi204N-linked (GlcNAc...)Sequence analysis1
Glycosylationi246N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi279 ↔ 464Curated

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP22894.
PeptideAtlasiP22894.
PRIDEiP22894.
TopDownProteomicsiP22894.

PTM databases

iPTMnetiP22894.
PhosphoSitePlusiP22894.

Miscellaneous databases

PMAP-CutDBP22894.

Expressioni

Tissue specificityi

Neutrophils.

Gene expression databases

BgeeiENSG00000118113.
CleanExiHS_MMP8.
ExpressionAtlasiP22894. baseline and differential.
GenevisibleiP22894. HS.

Organism-specific databases

HPAiHPA021221.
HPA022935.

Interactioni

Protein-protein interaction databases

BioGridi110460. 1 interactor.
STRINGi9606.ENSP00000236826.

Chemistry databases

BindingDBiP22894.

Structurei

Secondary structure

1467
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi107 – 109Combined sources3
Beta strandi111 – 117Combined sources7
Beta strandi122 – 124Combined sources3
Helixi126 – 141Combined sources16
Beta strandi147 – 150Combined sources4
Beta strandi152 – 154Combined sources3
Beta strandi157 – 163Combined sources7
Beta strandi168 – 170Combined sources3
Beta strandi175 – 178Combined sources4
Beta strandi181 – 183Combined sources3
Beta strandi186 – 188Combined sources3
Turni189 – 192Combined sources4
Beta strandi194 – 197Combined sources4
Beta strandi203 – 208Combined sources6
Helixi211 – 223Combined sources13
Beta strandi236 – 238Combined sources3
Beta strandi244 – 246Combined sources3
Helixi251 – 261Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A85X-ray2.00A105-262[»]
1A86X-ray2.00A105-262[»]
1BZSX-ray1.70A99-262[»]
1I73X-ray1.40A100-262[»]
1I76X-ray1.20A100-262[»]
1JANX-ray2.50A99-262[»]
1JAOX-ray2.40A100-262[»]
1JAPX-ray1.82A100-262[»]
1JAQX-ray2.40A100-262[»]
1JH1X-ray2.70A105-262[»]
1JJ9X-ray2.00A100-262[»]
1KBCX-ray1.80A/B99-262[»]
1MMBX-ray2.10A100-262[»]
1MNCX-ray2.10A101-263[»]
1ZP5X-ray1.80A100-262[»]
1ZS0X-ray1.56A100-262[»]
1ZVXX-ray1.87A100-262[»]
2OY2X-ray1.50A/F105-262[»]
2OY4X-ray1.70A/F105-262[»]
3DNGX-ray2.00A/B100-262[»]
3DPEX-ray1.60A100-262[»]
3DPFX-ray2.10A/B100-262[»]
3TT4X-ray1.88A104-262[»]
4QKZX-ray1.20A100-262[»]
ProteinModelPortaliP22894.
SMRiP22894.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22894.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati276 – 325Hemopexin 1Add BLAST50
Repeati326 – 372Hemopexin 2Add BLAST47
Repeati374 – 420Hemopexin 3Add BLAST47
Repeati421 – 464Hemopexin 4Add BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi89 – 96Cysteine switchBy similarity8

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

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiP22894.
KOiK01402.
OMAiEETWTKT.
OrthoDBiEOG091G03DP.
PhylomeDBiP22894.
TreeFamiTF315428.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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.

P22894-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFSLKTLPFL LLLHVQISKA FPVSSKEKNT KTVQDYLEKF YQLPSNQYQS
60 70 80 90 100
TRKNGTNVIV EKLKEMQRFF GLNVTGKPNE ETLDMMKKPR CGVPDSGGFM
110 120 130 140 150
LTPGNPKWER TNLTYRIRNY TPQLSEAEVE RAIKDAFELW SVASPLIFTR
160 170 180 190 200
ISQGEADINI AFYQRDHGDN SPFDGPNGIL AHAFQPGQGI GGDAHFDAEE
210 220 230 240 250
TWTNTSANYN LFLVAAHEFG HSLGLAHSSD PGALMYPNYA FRETSNYSLP
260 270 280 290 300
QDDIDGIQAI YGLSSNPIQP TGPSTPKPCD PSLTFDAITT LRGEILFFKD
310 320 330 340 350
RYFWRRHPQL QRVEMNFISL FWPSLPTGIQ AAYEDFDRDL IFLFKGNQYW
360 370 380 390 400
ALSGYDILQG YPKDISNYGF PSSVQAIDAA VFYRSKTYFF VNDQFWRYDN
410 420 430 440 450
QRQFMEPGYP KSISGAFPGI ESKVDAVFQQ EHFFHVFSGP RYYAFDLIAQ
460
RVTRVARGNK WLNCRYG
Length:467
Mass (Da):53,412
Last modified:August 1, 1991 - v1
Checksum:i4D4602A53AD7F8BC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40F → I AA sequence (PubMed:2159879).Curated1
Sequence conflicti48Y → V AA sequence (PubMed:2159879).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0250363S → C.1 PublicationCorresponds to variant rs17099450dbSNPEnsembl.1
Natural variantiVAR_02503732T → I.2 PublicationsCorresponds to variant rs3765620dbSNPEnsembl.1
Natural variantiVAR_00673087K → E.1 PublicationCorresponds to variant rs1940475dbSNPEnsembl.1
Natural variantiVAR_025038154G → E.1 PublicationCorresponds to variant rs35056226dbSNPEnsembl.1
Natural variantiVAR_025039193D → V.1 PublicationCorresponds to variant rs34428739dbSNPEnsembl.1
Natural variantiVAR_025040246N → Y.1 PublicationCorresponds to variant rs35243553dbSNPEnsembl.1
Natural variantiVAR_025041436V → A.1 PublicationCorresponds to variant rs34009635dbSNPEnsembl.1
Natural variantiVAR_025042460K → T.1 PublicationCorresponds to variant rs35866072dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05556 mRNA. Translation: AAA88021.1.
DQ141306 Genomic DNA. Translation: AAZ38714.1.
BC074988 mRNA. Translation: AAH74988.1.
BC074989 mRNA. Translation: AAH74989.1.
CCDSiCCDS8320.1.
PIRiA37073. KCHUN.
RefSeqiNP_001291370.1. NM_001304441.1.
NP_001291371.1. NM_001304442.1.
NP_002415.1. NM_002424.2.
UniGeneiHs.161839.

Genome annotation databases

EnsembliENST00000236826; ENSP00000236826; ENSG00000118113.
GeneIDi4317.
KEGGihsa:4317.
UCSCiuc001phe.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05556 mRNA. Translation: AAA88021.1.
DQ141306 Genomic DNA. Translation: AAZ38714.1.
BC074988 mRNA. Translation: AAH74988.1.
BC074989 mRNA. Translation: AAH74989.1.
CCDSiCCDS8320.1.
PIRiA37073. KCHUN.
RefSeqiNP_001291370.1. NM_001304441.1.
NP_001291371.1. NM_001304442.1.
NP_002415.1. NM_002424.2.
UniGeneiHs.161839.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A85X-ray2.00A105-262[»]
1A86X-ray2.00A105-262[»]
1BZSX-ray1.70A99-262[»]
1I73X-ray1.40A100-262[»]
1I76X-ray1.20A100-262[»]
1JANX-ray2.50A99-262[»]
1JAOX-ray2.40A100-262[»]
1JAPX-ray1.82A100-262[»]
1JAQX-ray2.40A100-262[»]
1JH1X-ray2.70A105-262[»]
1JJ9X-ray2.00A100-262[»]
1KBCX-ray1.80A/B99-262[»]
1MMBX-ray2.10A100-262[»]
1MNCX-ray2.10A101-263[»]
1ZP5X-ray1.80A100-262[»]
1ZS0X-ray1.56A100-262[»]
1ZVXX-ray1.87A100-262[»]
2OY2X-ray1.50A/F105-262[»]
2OY4X-ray1.70A/F105-262[»]
3DNGX-ray2.00A/B100-262[»]
3DPEX-ray1.60A100-262[»]
3DPFX-ray2.10A/B100-262[»]
3TT4X-ray1.88A104-262[»]
4QKZX-ray1.20A100-262[»]
ProteinModelPortaliP22894.
SMRiP22894.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110460. 1 interactor.
STRINGi9606.ENSP00000236826.

Chemistry databases

BindingDBiP22894.
ChEMBLiCHEMBL4588.
DrugBankiDB00786. Marimastat.
GuidetoPHARMACOLOGYi1632.

Protein family/group databases

MEROPSiM10.002.

PTM databases

iPTMnetiP22894.
PhosphoSitePlusiP22894.

Polymorphism and mutation databases

BioMutaiMMP8.
DMDMi116862.

Proteomic databases

PaxDbiP22894.
PeptideAtlasiP22894.
PRIDEiP22894.
TopDownProteomicsiP22894.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236826; ENSP00000236826; ENSG00000118113.
GeneIDi4317.
KEGGihsa:4317.
UCSCiuc001phe.2. human.

Organism-specific databases

CTDi4317.
DisGeNETi4317.
GeneCardsiMMP8.
HGNCiHGNC:7175. MMP8.
HPAiHPA021221.
HPA022935.
MalaCardsiMMP8.
MIMi120355. gene.
neXtProtiNX_P22894.
OpenTargetsiENSG00000118113.
PharmGKBiPA30888.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiP22894.
KOiK01402.
OMAiEETWTKT.
OrthoDBiEOG091G03DP.
PhylomeDBiP22894.
TreeFamiTF315428.

Enzyme and pathway databases

BioCyciZFISH:HS04191-MONOMER.
BRENDAi3.4.24.34. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiP22894.
GeneWikiiMMP8.
GenomeRNAii4317.
PMAP-CutDBP22894.
PROiP22894.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118113.
CleanExiHS_MMP8.
ExpressionAtlasiP22894. baseline and differential.
GenevisibleiP22894. HS.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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...

Entry informationi

Entry nameiMMP8_HUMAN
AccessioniPrimary (citable) accession number: P22894
Secondary accession number(s): Q45F99
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 30, 2016
This is version 176 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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 one 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.