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Protein

Neutrophil collagenase

Gene

MMP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Activity 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

  • endopeptidase activity Source: ARUK-UCL
  • metalloendopeptidase activity Source: Reactome
  • serine-type endopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCollagen degradation
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000118113.11
HGNCiHGNC:7175 MMP8
MIMi120355 gene
neXtProtiNX_P22894

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4317
MalaCardsiMMP8
OpenTargetsiENSG00000118113
PharmGKBiPA30888

Chemistry databases

ChEMBLiCHEMBL4588
DrugBankiDB02326 1-Hydroxyamine-2-Isobutylmalonic Acid
DB02953 2-Thiomethyl-3-Phenylpropanoic Acid
DB08476 3-AMINO-AZACYCLOTRIDECAN-2-ONE
DB07900 3-FORMYL-2-HYDROXY-5-METHYL-HEXANOIC ACID HYDROXYAMIDE
DB03880 Batimastat
DB03636 Glycinamid
DB00786 Marimastat
DB08403 METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID
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...) asparagineCurated1
Glycosylationi73N-linked (GlcNAc...) asparagineCurated1
Glycosylationi112N-linked (GlcNAc...) asparagine1
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi246N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi279 ↔ 464Curated

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP22894
PeptideAtlasiP22894
PRIDEiP22894
ProteomicsDBi54047
TopDownProteomicsiP22894

PTM databases

iPTMnetiP22894
PhosphoSitePlusiP22894

Miscellaneous databases

PMAP-CutDBiP22894

Expressioni

Tissue specificityi

Neutrophils.

Gene expression databases

BgeeiENSG00000118113 Expressed in 79 organ(s), highest expression level in bone marrow
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

3D structure databases

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

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
Gene3Di1.10.101.10, 1 hit
2.110.10.10, 1 hit
3.40.390.10, 2 hits
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028709 MMP8
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021158 Pept_M10A_Zn_BS
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
IPR036366 PGBDSf
PANTHERiPTHR10201:SF137 PTHR10201:SF137, 1 hit
PfamiView protein in Pfam
PF00045 Hemopexin, 3 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00546 CYSTEINE_SWITCH, 1 hit
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C1M3H7C1M3_HUMAN
Matrix metalloproteinase
MMP8
344Annotation score:
E9PJB3E9PJB3_HUMAN
Matrix metalloproteinase
MMP8
56Annotation score:
E9PL87E9PL87_HUMAN
Matrix metalloproteinase
MMP8
36Annotation score:
E9PIY7E9PIY7_HUMAN
Matrix metalloproteinase
MMP8
43Annotation score:

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 → C1 PublicationCorresponds to variant dbSNP:rs17099450Ensembl.1
Natural variantiVAR_02503732T → I2 PublicationsCorresponds to variant dbSNP:rs3765620EnsemblClinVar.1
Natural variantiVAR_00673087K → E1 PublicationCorresponds to variant dbSNP:rs1940475EnsemblClinVar.1
Natural variantiVAR_025038154G → E1 PublicationCorresponds to variant dbSNP:rs35056226Ensembl.1
Natural variantiVAR_025039193D → V1 PublicationCorresponds to variant dbSNP:rs34428739Ensembl.1
Natural variantiVAR_025040246N → Y1 PublicationCorresponds to variant dbSNP:rs35243553Ensembl.1
Natural variantiVAR_025041436V → A1 PublicationCorresponds to variant dbSNP:rs34009635Ensembl.1
Natural variantiVAR_025042460K → T1 PublicationCorresponds to variant dbSNP:rs35866072Ensembl.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

Similar proteinsi

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[»]
5H8XX-ray1.30A100-262[»]
ProteinModelPortaliP22894
SMRiP22894
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110460, 1 interactor
STRINGi9606.ENSP00000236826

Chemistry databases

BindingDBiP22894
ChEMBLiCHEMBL4588
DrugBankiDB02326 1-Hydroxyamine-2-Isobutylmalonic Acid
DB02953 2-Thiomethyl-3-Phenylpropanoic Acid
DB08476 3-AMINO-AZACYCLOTRIDECAN-2-ONE
DB07900 3-FORMYL-2-HYDROXY-5-METHYL-HEXANOIC ACID HYDROXYAMIDE
DB03880 Batimastat
DB03636 Glycinamid
DB00786 Marimastat
DB08403 METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID
GuidetoPHARMACOLOGYi1632

Protein family/group databases

MEROPSiM10.002

PTM databases

iPTMnetiP22894
PhosphoSitePlusiP22894

Polymorphism and mutation databases

BioMutaiMMP8
DMDMi116862

Proteomic databases

PaxDbiP22894
PeptideAtlasiP22894
PRIDEiP22894
ProteomicsDBi54047
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
EuPathDBiHostDB:ENSG00000118113.11
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

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-CutDBiP22894
PROiPR:P22894
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118113 Expressed in 79 organ(s), highest expression level in bone marrow
CleanExiHS_MMP8
ExpressionAtlasiP22894 baseline and differential
GenevisibleiP22894 HS

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di1.10.101.10, 1 hit
2.110.10.10, 1 hit
3.40.390.10, 2 hits
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028709 MMP8
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021158 Pept_M10A_Zn_BS
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
IPR036366 PGBDSf
PANTHERiPTHR10201:SF137 PTHR10201:SF137, 1 hit
PfamiView protein in Pfam
PF00045 Hemopexin, 3 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00546 CYSTEINE_SWITCH, 1 hit
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMMP8_HUMAN
AccessioniPrimary (citable) accession number: P22894
Secondary accession number(s): Q45F99
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 7, 2018
This is version 190 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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