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Protein

Collagenase 3

Gene

Mmp13

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

Functioni

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.5 Publications

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi97Zinc 2; in inhibited formBy similarity1
Metal bindingi129Calcium 1By similarity1
Metal bindingi163Calcium 2; via carbonyl oxygen1
Metal bindingi173Zinc 1; via tele nitrogen1 Publication1
Metal bindingi175Zinc 11 Publication1
Metal bindingi180Calcium 31
Metal bindingi181Calcium 3; via carbonyl oxygen1
Metal bindingi183Calcium 3; via carbonyl oxygen1
Metal bindingi185Calcium 3; via carbonyl oxygen1
Metal bindingi188Zinc 1; via tele nitrogen1 Publication1
Metal bindingi195Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi197Calcium 2; via carbonyl oxygen1
Metal bindingi199Calcium 2By similarity1
Metal bindingi201Zinc 1; via pros nitrogen1 Publication1
Metal bindingi203Calcium 31
Metal bindingi204Calcium 1By similarity1
Metal bindingi206Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi206Calcium 31
Metal bindingi223Zinc 2; via tele nitrogen; catalytic1 Publication1
Active sitei2241
Metal bindingi227Zinc 2; via tele nitrogen; catalytic1 Publication1
Metal bindingi233Zinc 2; via tele nitrogen; catalytic1 Publication1
Metal bindingi241Zinc 2; via carbonyl oxygen; catalyticBy similarity1
Metal bindingi292Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi294Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi336Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi338Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi384Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi386Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi433Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi435Calcium 5; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • collagen binding Source: UniProtKB
  • metalloendopeptidase activity Source: MGI
  • peptidase activity Source: MGI
  • serine-type endopeptidase activity Source: Reactome
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • bone mineralization Source: UniProtKB
  • bone morphogenesis Source: UniProtKB
  • cartilage development Source: MGI
  • cellular protein metabolic process Source: MGI
  • collagen catabolic process Source: UniProtKB
  • endochondral ossification Source: UniProtKB
  • extracellular matrix disassembly Source: UniProtKB
  • growth plate cartilage development Source: MGI
  • 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

BRENDAi3.4.24.B4. 3474.
ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474228. Degradation of the extracellular matrix.
R-MMU-1592389. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.013.

Names & Taxonomyi

Protein namesi
Recommended name:
Collagenase 3 (EC:3.4.24.-)
Alternative name(s):
Matrix metalloproteinase-13
Short name:
MMP-13
Gene namesi
Name:Mmp13
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1340026. Mmp13.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Disruption phenotypei

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 (PubMed:15563592). 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 (PubMed:15563592 and PubMed:15539485), but one year old mutant mice display no longer any difference relative to wild-type (PubMed:15539485). 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 Mmp9.5 Publications

Chemistry databases

ChEMBLiCHEMBL3638350.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000002879020 – 104Activation peptide1 PublicationAdd BLAST85
ChainiPRO_0000028791105 – 472Collagenase 3Add BLAST368

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi118N-linked (GlcNAc...)Sequence analysis1
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi285 ↔ 472By similarity
Modified residuei367Phosphotyrosine; by PKDCCBy similarity1
Glycosylationi410N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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).By similarity
N-glycosylated.By similarity
Tyrosine phosphorylated by PKDCC/VLK.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiP33435.
PRIDEiP33435.

PTM databases

PhosphoSitePlusiP33435.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiENSMUSG00000050578.
CleanExiMM_MMP13.
ExpressionAtlasiP33435. baseline and differential.
GenevisibleiP33435. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000015394.

Chemistry databases

BindingDBiP33435.

Structurei

Secondary structure

1472
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi117 – 123Combined sources7
Helixi132 – 147Combined sources16
Beta strandi153 – 156Combined sources4
Beta strandi158 – 160Combined sources3
Beta strandi163 – 169Combined sources7
Beta strandi174 – 176Combined sources3
Beta strandi181 – 184Combined sources4
Beta strandi187 – 189Combined sources3
Beta strandi192 – 194Combined sources3
Turni195 – 198Combined sources4
Beta strandi200 – 203Combined sources4
Beta strandi208 – 216Combined sources9
Helixi217 – 229Combined sources13
Beta strandi242 – 244Combined sources3
Helixi257 – 267Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CXVX-ray2.00A/B105-268[»]
ProteinModelPortaliP33435.
SMRiP33435.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP33435.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati282 – 331Hemopexin 1Add BLAST50
Repeati332 – 378Hemopexin 2Add BLAST47
Repeati380 – 428Hemopexin 3Add BLAST49
Repeati429 – 472Hemopexin 4Add BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni177 – 247Interaction with TIMP2By similarityAdd BLAST71
Regioni269 – 472Interaction with collagenBy similarityAdd BLAST204

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi95 – 102Cysteine 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 (By similarity).By similarity
The C-terminal region binds to collagen.By similarity

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.
InParanoidiP33435.
KOiK07994.
OMAiMLPDDDV.
OrthoDBiEOG091G03DP.
PhylomeDBiP33435.
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.
InterProiIPR028711. Collagenase_3.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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]
PANTHERiPTHR10201:SF165. PTHR10201:SF165. 1 hit.
PfamiPF00045. Hemopexin. 4 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.

P33435-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHSAILATFF LLSWTPCWSL PLPYGDDDDD DLSEEDLVFA EHYLKSYYHP
60 70 80 90 100
ATLAGILKKS TVTSTVDRLR EMQSFFGLEV TGKLDDPTLD IMRKPRCGVP
110 120 130 140 150
DVGEYNVFPR TLKWSQTNLT YRIVNYTPDM SHSEVEKAFR KAFKVWSDVT
160 170 180 190 200
PLNFTRIYDG TADIMISFGT KEHGDFYPFD GPSGLLAHAF PPGPNYGGDA
210 220 230 240 250
HFDDDETWTS SSKGYNLFIV AAHELGHSLG LDHSKDPGAL MFPIYTYTGK
260 270 280 290 300
SHFMLPDDDV QGIQFLYGPG DEDPNPKHPK TPEKCDPALS LDAITSLRGE
310 320 330 340 350
TMIFKDRFFW RLHPQQVEAE LFLTKSFWPE LPNHVDAAYE HPSRDLMFIF
360 370 380 390 400
RGRKFWALNG YDILEGYPRK ISDLGFPKEV KRLSAAVHFE NTGKTLFFSE
410 420 430 440 450
NHVWSYDDVN QTMDKDYPRL IEEEFPGIGN KVDAVYEKNG YIYFFNGPIQ
460 470
FEYSIWSNRI VRVMPTNSIL WC
Length:472
Mass (Da):54,182
Last modified:February 1, 1994 - v1
Checksum:i67F437B89B4D0DBD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66473 mRNA. Translation: CAA47102.1.
CCDSiCCDS22803.1.
PIRiS29243.
RefSeqiNP_032633.1. NM_008607.2.
UniGeneiMm.5022.

Genome annotation databases

EnsembliENSMUST00000015394; ENSMUSP00000015394; ENSMUSG00000050578.
GeneIDi17386.
KEGGimmu:17386.
UCSCiuc009ocg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66473 mRNA. Translation: CAA47102.1.
CCDSiCCDS22803.1.
PIRiS29243.
RefSeqiNP_032633.1. NM_008607.2.
UniGeneiMm.5022.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CXVX-ray2.00A/B105-268[»]
ProteinModelPortaliP33435.
SMRiP33435.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000015394.

Chemistry databases

BindingDBiP33435.
ChEMBLiCHEMBL3638350.

Protein family/group databases

MEROPSiM10.013.

PTM databases

PhosphoSitePlusiP33435.

Proteomic databases

PaxDbiP33435.
PRIDEiP33435.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015394; ENSMUSP00000015394; ENSMUSG00000050578.
GeneIDi17386.
KEGGimmu:17386.
UCSCiuc009ocg.2. mouse.

Organism-specific databases

CTDi4322.
MGIiMGI:1340026. Mmp13.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217927.
HOVERGENiHBG052484.
InParanoidiP33435.
KOiK07994.
OMAiMLPDDDV.
OrthoDBiEOG091G03DP.
PhylomeDBiP33435.
TreeFamiTF315428.

Enzyme and pathway databases

BRENDAi3.4.24.B4. 3474.
ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474228. Degradation of the extracellular matrix.
R-MMU-1592389. Activation of Matrix Metalloproteinases.

Miscellaneous databases

ChiTaRSiMmp13. mouse.
EvolutionaryTraceiP33435.
PROiP33435.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000050578.
CleanExiMM_MMP13.
ExpressionAtlasiP33435. baseline and differential.
GenevisibleiP33435. MM.

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.
InterProiIPR028711. Collagenase_3.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
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]
PANTHERiPTHR10201:SF165. PTHR10201:SF165. 1 hit.
PfamiPF00045. Hemopexin. 4 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 nameiMMP13_MOUSE
AccessioniPrimary (citable) accession number: P33435
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. 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.