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P22894 (MMP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MMP8
Synonyms:CLG1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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.

Cofactor

Binds 3 calcium ions per subunit.

Binds 2 zinc ions per subunit.

Enzyme regulation

Cannot be activated without removal of the activation peptide.

Subcellular location

Cytoplasmic granule. Secretedextracellular spaceextracellular matrix Probable. Note: Stored in intracellular granules.

Tissue specificity

Neutrophils.

Domain

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 similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.4 Ref.5
Propeptide21 – 10080Activation peptide
PRO_0000028744
Chain101 – 467367Neutrophil collagenase
PRO_0000028745

Regions

Repeat276 – 32550Hemopexin 1
Repeat326 – 37247Hemopexin 2
Repeat374 – 42047Hemopexin 3
Repeat421 – 46444Hemopexin 4
Motif89 – 968Cysteine switch By similarity

Sites

Active site2181
Metal binding911Zinc 2; in inhibited form
Metal binding1571Calcium 1
Metal binding1671Zinc 1 Ref.10
Metal binding1691Zinc 1 Ref.10
Metal binding1741Calcium 2 Ref.10
Metal binding1751Calcium 2; via carbonyl oxygen Ref.10
Metal binding1771Calcium 2; via carbonyl oxygen Ref.10
Metal binding1791Calcium 2; via carbonyl oxygen Ref.10
Metal binding1821Zinc 1 Ref.10
Metal binding1891Calcium 1; via carbonyl oxygen
Metal binding1911Calcium 1; via carbonyl oxygen
Metal binding1931Calcium 1
Metal binding1951Zinc 1 Ref.10
Metal binding1971Calcium 2 Ref.10
Metal binding2001Calcium 2 Ref.10
Metal binding2171Zinc 2; catalytic Ref.10
Metal binding2211Zinc 2; catalytic Ref.10
Metal binding2271Zinc 2; catalytic Ref.10
Metal binding2861Calcium 3; via carbonyl oxygen By similarity
Metal binding3781Calcium 3; via carbonyl oxygen By similarity
Metal binding4251Calcium 3; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation541N-linked (GlcNAc...) Probable
Glycosylation731N-linked (GlcNAc...) Probable
Glycosylation1121N-linked (GlcNAc...)
Glycosylation2041N-linked (GlcNAc...) Potential
Glycosylation2461N-linked (GlcNAc...) Potential
Disulfide bond279 ↔ 464 Probable

Natural variations

Natural variant31S → C. Ref.2
Corresponds to variant rs17099450 [ dbSNP | Ensembl ].
VAR_025036
Natural variant321T → I. Ref.2 Ref.4
Corresponds to variant rs3765620 [ dbSNP | Ensembl ].
VAR_025037
Natural variant871K → E. Ref.2
Corresponds to variant rs1940475 [ dbSNP | Ensembl ].
VAR_006730
Natural variant1541G → E. Ref.2
Corresponds to variant rs35056226 [ dbSNP | Ensembl ].
VAR_025038
Natural variant1931D → V. Ref.2
Corresponds to variant rs34428739 [ dbSNP | Ensembl ].
VAR_025039
Natural variant2461N → Y. Ref.2
Corresponds to variant rs35243553 [ dbSNP | Ensembl ].
VAR_025040
Natural variant4361V → A. Ref.2
Corresponds to variant rs34009635 [ dbSNP | Ensembl ].
VAR_025041
Natural variant4601K → T. Ref.2
Corresponds to variant rs35866072 [ dbSNP | Ensembl ].
VAR_025042

Experimental info

Sequence conflict401F → I AA sequence Ref.4
Sequence conflict481Y → V AA sequence Ref.4

Secondary structure

.................................... 467
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22894 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 4D4602A53AD7F8BC

FASTA46753,412
        10         20         30         40         50         60 
MFSLKTLPFL LLLHVQISKA FPVSSKEKNT KTVQDYLEKF YQLPSNQYQS TRKNGTNVIV 

        70         80         90        100        110        120 
EKLKEMQRFF GLNVTGKPNE ETLDMMKKPR CGVPDSGGFM LTPGNPKWER TNLTYRIRNY 

       130        140        150        160        170        180 
TPQLSEAEVE RAIKDAFELW SVASPLIFTR ISQGEADINI AFYQRDHGDN SPFDGPNGIL 

       190        200        210        220        230        240 
AHAFQPGQGI GGDAHFDAEE TWTNTSANYN LFLVAAHEFG HSLGLAHSSD PGALMYPNYA 

       250        260        270        280        290        300 
FRETSNYSLP QDDIDGIQAI YGLSSNPIQP TGPSTPKPCD PSLTFDAITT LRGEILFFKD 

       310        320        330        340        350        360 
RYFWRRHPQL QRVEMNFISL FWPSLPTGIQ AAYEDFDRDL IFLFKGNQYW ALSGYDILQG 

       370        380        390        400        410        420 
YPKDISNYGF PSSVQAIDAA VFYRSKTYFF VNDQFWRYDN QRQFMEPGYP KSISGAFPGI 

       430        440        450        460 
ESKVDAVFQQ EHFFHVFSGP RYYAFDLIAQ RVTRVARGNK WLNCRYG 

« Hide

References

« Hide 'large scale' references
[1]"Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases."
Hasty K.A., Pourmotabbed T.F., Goldberg G.I., Thompson J.P., Spinella D.G., Stevens R.M., Mainardi C.L.
J. Biol. Chem. 265:11421-11424(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 314-337; 347-363 AND 424-441.
Tissue: Neutrophil.
[2]NIEHS SNPs program
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-3; ILE-32; GLU-87; GLU-154; VAL-193; TYR-246; ALA-436 AND THR-460.
[3]"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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[4]"Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms."
Knaeuper V., Kraemer S., Reinke H., Tschesche H.
Eur. J. Biochem. 189:295-300(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-140, VARIANT ILE-32.
Tissue: Neutrophil.
[5]"Mercurial activation of human polymorphonuclear leucocyte procollagenase."
Blaeser J., Knaeuper V., Osthues A., Reinke H., Tschesche H.
Eur. J. Biochem. 202:1223-1230(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-103.
Tissue: Neutrophil.
[6]"Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase."
Mallya S.K., Mookthiar K.A., Gao Y., Brew K., Dioszegi M., Birkedal-Hansen H., van Wart H.E.
Biochemistry 29:10628-10634(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 85-120, CHARACTERIZATION.
Tissue: Neutrophil.
[7]"Partial amino acid sequence of human PMN leukocyte procollagenase."
Knaeuper V., Kraemer S., Reinke H., Tschesche H.
Biol. Chem. Hoppe-Seyler 371:295-304(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[8]Erratum
Knaeuper V., Kraemer S., Reinke H., Tschesche H.
Biol. Chem. Hoppe-Seyler 371:733-733(1990) [PubMed] [Europe PMC] [Abstract]
[9]"Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL procollagenase gives evidence of a cysteine-switch mechanism."
Blaeser J., Triebel S., Reinke H., Tschesche H.
FEBS Lett. 313:59-61(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: CYSTEINE-SWITCH MECHANISM.
Tissue: Neutrophil.
[10]"The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity."
Bode W., Reinemer P., Huber R., Klein T., Schnierer S., Tschesche H.
EMBO J. 13:1263-1269(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-262.
[11]"Structural implications for the role of the N-terminus in the 'superactivation' of collagenases. A crystallographic study."
Reinemer P., Grams F., Huber R., Kleine T., Schnierer S., Piper M., Tschesche H., Bode W.
FEBS Lett. 338:227-233(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 100-262.
[12]"Structure of human neutrophil collagenase reveals large S1' specificity pocket."
Stams T., Spurlino J.C., Smith D.L., Wahl R.C., Ho T.F., Qoronfleh M.W., Banks T.M., Rubin B.
Nat. Struct. Biol. 1:119-123(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 100-262.
[13]"1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile."
Betz M., Huxley P., Davies S.J., Mushtaq Y., Pieper M., Tschesche H., Bode W., Gomis-Rueth F.-X.
Eur. J. Biochem. 247:356-363(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 100-262.
[14]"Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data."
Brandstetter H., Engh R.A., von Roedern E.G., Moroder L., Huber R., Bode W., Grams F.
Protein Sci. 7:1303-1309(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-262.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05556 mRNA. Translation: AAA88021.1.
DQ141306 Genomic DNA. Translation: AAZ38714.1.
BC074988 mRNA. Translation: AAH74988.1.
BC074989 mRNA. Translation: AAH74989.1.
CCDSCCDS8320.1.
PIRKCHUN. A37073.
RefSeqNP_002415.1. NM_002424.2.
UniGeneHs.161839.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP22894.
SMRP22894. Positions 33-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110460. 2 interactions.
STRING9606.ENSP00000236826.

Chemistry

BindingDBP22894.
ChEMBLCHEMBL2095216.
GuidetoPHARMACOLOGY1632.

Protein family/group databases

MEROPSM10.002.

PTM databases

PhosphoSiteP22894.

Polymorphism databases

DMDM116862.

Proteomic databases

PaxDbP22894.
PeptideAtlasP22894.
PRIDEP22894.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000236826; ENSP00000236826; ENSG00000118113.
GeneID4317.
KEGGhsa:4317.
UCSCuc001phe.2. human.

Organism-specific databases

CTD4317.
GeneCardsGC11M102617.
HGNCHGNC:7175. MMP8.
HPAHPA021221.
HPA022935.
MIM120355. gene.
neXtProtNX_P22894.
PharmGKBPA30888.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258253.
HOGENOMHOG000217927.
HOVERGENHBG052484.
InParanoidP22894.
KOK01402.
OMAYAFREPS.
OrthoDBEOG7XPZ57.
PhylomeDBP22894.
TreeFamTF315428.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressP22894.
BgeeP22894.
CleanExHS_MMP8.
GenevestigatorP22894.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. 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]
PANTHERPTHR10201:SF137. PTHR10201:SF137. 1 hit.
PfamPF00045. Hemopexin. 3 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSPR00138. MATRIXIN.
SMARTSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22894.
GeneWikiMMP8.
GenomeRNAi4317.
NextBio16985.
PMAP-CutDBP22894.
PROP22894.
SOURCESearch...

Entry information

Entry nameMMP8_HUMAN
AccessionPrimary (citable) accession number: P22894
Secondary accession number(s): Q45F99
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: July 9, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM