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P33435 (MMP13_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Collagenase 3

EC=3.4.24.-
Alternative name(s):
Matrix metalloproteinase-13
Short name=MMP-13
Gene names
Name:Mmp13
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length472 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6

Cofactor

Calcium. Can bind about 5 calcium ions per subunit. Ref.7

Binds 2 zinc ions per subunit. Ref.7

Subcellular location

Secretedextracellular spaceextracellular matrix Probable. Secreted Ref.2 Ref.3.

Tissue specificity

Detected in epidermal cells and stromal fibroblasts in wounded skin, but not in normal skin (at protein level). Detected in embryonic hypertrophic chondrocytes and newly recruited bone cells at primary ossification centers. After adult bone fracture, detected in periosteum and in chondrocytes in the cartilage. Detected in immature and mature osteoblasts in the fracture callus. Detected in calvaria from neonates. Detected in wounded skin, but not in normal skin. Ref.3 Ref.4 Ref.5

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 By similarity.

The C-terminal region binds to collagen By similarity.

Post-translational modification

The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro) By similarity.

N-glycosylated By similarity.

Disruption phenotype

No visible phenotype. Mice are born at the expected Mendelian rate, are fertile and have a normal life span. Mutant embryos show a delay in the development of the primary ossification centers. Besides, they display an increased length of the growth plates of the long bones from the hind limbs (Ref.3). Three week old mutant mice display an increased trabecular bone volume due to an increase in the length of the hypertrophic chondrocyte zone of the growth plate. This phenotype persists during several months (Ref.3 and Ref.2), but one year old mutant mice display no longer any difference relative to wild-type (Ref.2). After bone fractures, mutant mice show delays in carticage remodeling and resorption, as well as an increased volume of spongy bone mass. In addition, mutant mice show delayed healing of cutaneous wounds that is most evident three to seven days after wounding. The delay in wound healing and in re-epithelialization is exacerbated in mice lacking both Mmp13 and Mmp9. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Ontologies

Keywords
   Biological processCollagen degradation
   Cellular componentExtracellular matrix
Secreted
   DomainRepeat
Signal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbone mineralization

Inferred from mutant phenotype Ref.4. Source: UniProtKB

bone morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cartilage development

Inferred from mutant phenotype PubMed 15581614. Source: MGI

cellular protein metabolic process

Inferred from direct assay PubMed 11953314. Source: MGI

collagen catabolic process

Inferred from mutant phenotype Ref.4. Source: UniProtKB

endochondral ossification

Inferred from mutant phenotype Ref.4. Source: UniProtKB

extracellular matrix disassembly

Inferred from mutant phenotype Ref.4. Source: UniProtKB

proteolysis

Inferred from mutant phenotype Ref.4. Source: UniProtKB

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

collagen binding

Inferred from sequence or structural similarity. Source: UniProtKB

metalloendopeptidase activity

Inferred from direct assay PubMed 11953314PubMed 14702107. Source: MGI

peptidase activity

Inferred from direct assay PubMed 15581614. Source: MGI

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 10485Activation peptide
PRO_0000028790
Chain105 – 472368Collagenase 3
PRO_0000028791

Regions

Repeat282 – 33150Hemopexin 1
Repeat332 – 37847Hemopexin 2
Repeat380 – 42849Hemopexin 3
Repeat429 – 47244Hemopexin 4
Region177 – 24771Interaction with TIMP2 By similarity
Region269 – 472204Interaction with collagen By similarity
Motif95 – 1028Cysteine switch By similarity

Sites

Active site2241
Metal binding971Zinc 2; in inhibited form By similarity
Metal binding1291Calcium 1 By similarity
Metal binding1631Calcium 2; via carbonyl oxygen
Metal binding1731Zinc 1; via tele nitrogen
Metal binding1751Zinc 1
Metal binding1801Calcium 3
Metal binding1811Calcium 3; via carbonyl oxygen
Metal binding1831Calcium 3; via carbonyl oxygen
Metal binding1851Calcium 3; via carbonyl oxygen
Metal binding1881Zinc 1; via tele nitrogen
Metal binding1951Calcium 2; via carbonyl oxygen By similarity
Metal binding1971Calcium 2; via carbonyl oxygen
Metal binding1991Calcium 2 By similarity
Metal binding2011Zinc 1; via pros nitrogen
Metal binding2031Calcium 3
Metal binding2041Calcium 1 By similarity
Metal binding2061Calcium 1; via carbonyl oxygen By similarity
Metal binding2061Calcium 3
Metal binding2231Zinc 2; via tele nitrogen; catalytic
Metal binding2271Zinc 2; via tele nitrogen; catalytic
Metal binding2331Zinc 2; via tele nitrogen; catalytic
Metal binding2411Zinc 2; via carbonyl oxygen; catalytic By similarity
Metal binding2921Calcium 4; via carbonyl oxygen By similarity
Metal binding2941Calcium 5; via carbonyl oxygen By similarity
Metal binding3361Calcium 4; via carbonyl oxygen By similarity
Metal binding3381Calcium 5; via carbonyl oxygen By similarity
Metal binding3841Calcium 4; via carbonyl oxygen By similarity
Metal binding3861Calcium 5; via carbonyl oxygen By similarity
Metal binding4331Calcium 4; via carbonyl oxygen By similarity
Metal binding4351Calcium 5; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation1181N-linked (GlcNAc...) Potential
Glycosylation1531N-linked (GlcNAc...) Potential
Glycosylation4101N-linked (GlcNAc...) Potential
Disulfide bond285 ↔ 472 By similarity

Secondary structure

............................. 472
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P33435 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 67F437B89B4D0DBD

FASTA47254,182
        10         20         30         40         50         60 
MHSAILATFF LLSWTPCWSL PLPYGDDDDD DLSEEDLVFA EHYLKSYYHP ATLAGILKKS 

        70         80         90        100        110        120 
TVTSTVDRLR EMQSFFGLEV TGKLDDPTLD IMRKPRCGVP DVGEYNVFPR TLKWSQTNLT 

       130        140        150        160        170        180 
YRIVNYTPDM SHSEVEKAFR KAFKVWSDVT PLNFTRIYDG TADIMISFGT KEHGDFYPFD 

       190        200        210        220        230        240 
GPSGLLAHAF PPGPNYGGDA HFDDDETWTS SSKGYNLFIV AAHELGHSLG LDHSKDPGAL 

       250        260        270        280        290        300 
MFPIYTYTGK SHFMLPDDDV QGIQFLYGPG DEDPNPKHPK TPEKCDPALS LDAITSLRGE 

       310        320        330        340        350        360 
TMIFKDRFFW RLHPQQVEAE LFLTKSFWPE LPNHVDAAYE HPSRDLMFIF RGRKFWALNG 

       370        380        390        400        410        420 
YDILEGYPRK ISDLGFPKEV KRLSAAVHFE NTGKTLFFSE NHVWSYDDVN QTMDKDYPRL 

       430        440        450        460        470 
IEEEFPGIGN KVDAVYEKNG YIYFFNGPIQ FEYSIWSNRI VRVMPTNSIL WC 

« Hide

References

[1]"Cloning and sequencing of mouse collagenase cDNA. Divergence of mouse and rat collagenases from the other mammalian collagenases."
Henriet P., Rousseau G.G., Eeckhout Y.
FEBS Lett. 310:175-178(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 105-119 AND 266-275.
Strain: NMRI.
Tissue: Calvaria.
[2]"Altered endochondral bone development in matrix metalloproteinase 13-deficient mice."
Stickens D., Behonick D.J., Ortega N., Heyer B., Hartenstein B., Yu Y., Fosang A.J., Schorpp-Kistner M., Angel P., Werb Z.
Development 131:5883-5895(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
[3]"Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification."
Inada M., Wang Y., Byrne M.H., Rahman M.U., Miyaura C., Lopez-Otin C., Krane S.M.
Proc. Natl. Acad. Sci. U.S.A. 101:17192-17197(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration."
Behonick D.J., Xing Z., Lieu S., Buckley J.M., Lotz J.C., Marcucio R.S., Werb Z., Miclau T., Colnot C.
PLoS ONE 2:E1150-E1150(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[5]"MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing."
Hattori N., Mochizuki S., Kishi K., Nakajima T., Takaishi H., D'Armiento J., Okada Y.
Am. J. Pathol. 175:533-546(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[6]"MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability."
Toriseva M., Laato M., Carpen O., Ruohonen S.T., Savontaus E., Inada M., Krane S.M., Kahari V.M.
PLoS ONE 7:E42596-E42596(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"Structure of recombinant mouse collagenase-3 (MMP-13)."
Botos I., Meyer E., Swanson S.M., Lemaitre V., Eeckhout Y., Meyer E.F.
J. Mol. Biol. 292:837-844(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-268 IN COMPLEX WITH ZINC AND CALCIUM IONS, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66473 mRNA. Translation: CAA47102.1.
CCDSCCDS22803.1.
PIRS29243.
RefSeqNP_032633.1. NM_008607.2.
UniGeneMm.5022.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CXVX-ray2.00A/B105-268[»]
ProteinModelPortalP33435.
SMRP33435. Positions 36-472.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSM10.013.

PTM databases

PhosphoSiteP33435.

Proteomic databases

PRIDEP33435.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000015394; ENSMUSP00000015394; ENSMUSG00000050578.
GeneID17386.
KEGGmmu:17386.
UCSCuc009ocg.2. mouse.

Organism-specific databases

CTD4322.
MGIMGI:1340026. Mmp13.

Phylogenomic databases

eggNOGNOG299356.
HOGENOMHOG000217927.
HOVERGENHBG052484.
InParanoidP33435.
KOK07994.
OMANQVWSYD.
OrthoDBEOG7XPZ57.
PhylomeDBP33435.
TreeFamTF315428.

Enzyme and pathway databases

ReactomeREACT_206066. Extracellular matrix organization.

Gene expression databases

ArrayExpressP33435.
BgeeP33435.
CleanExMM_MMP13.
GenevestigatorP33435.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR028711. Collagenase_3.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
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:SF130. PTHR10201:SF130. 1 hit.
PfamPF00045. Hemopexin. 4 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

ChiTaRSMMP13. mouse.
EvolutionaryTraceP33435.
NextBio291996.
PROP33435.
SOURCESearch...

Entry information

Entry nameMMP13_MOUSE
AccessionPrimary (citable) accession number: P33435
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot