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P33435

- MMP13_MOUSE

UniProt

P33435 - MMP13_MOUSE

Protein

Collagenase 3

Gene

Mmp13

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Feb 1994)
      Previous versions | rss
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    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

    Calcium. Can bind about 5 calcium ions per subunit.1 Publication
    Binds 2 zinc ions per subunit.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi97 – 971Zinc 2; in inhibited formBy similarity
    Metal bindingi129 – 1291Calcium 1By similarity
    Metal bindingi163 – 1631Calcium 2; via carbonyl oxygen
    Metal bindingi173 – 1731Zinc 1; via tele nitrogen1 Publication
    Metal bindingi175 – 1751Zinc 11 Publication
    Metal bindingi180 – 1801Calcium 3
    Metal bindingi181 – 1811Calcium 3; via carbonyl oxygen
    Metal bindingi183 – 1831Calcium 3; via carbonyl oxygen
    Metal bindingi185 – 1851Calcium 3; via carbonyl oxygen
    Metal bindingi188 – 1881Zinc 1; via tele nitrogen1 Publication
    Metal bindingi195 – 1951Calcium 2; via carbonyl oxygenBy similarity
    Metal bindingi197 – 1971Calcium 2; via carbonyl oxygen
    Metal bindingi199 – 1991Calcium 2By similarity
    Metal bindingi201 – 2011Zinc 1; via pros nitrogen1 Publication
    Metal bindingi203 – 2031Calcium 3
    Metal bindingi204 – 2041Calcium 1By similarity
    Metal bindingi206 – 2061Calcium 1; via carbonyl oxygenBy similarity
    Metal bindingi206 – 2061Calcium 3
    Metal bindingi223 – 2231Zinc 2; via tele nitrogen; catalytic1 Publication
    Active sitei224 – 2241
    Metal bindingi227 – 2271Zinc 2; via tele nitrogen; catalytic1 Publication
    Metal bindingi233 – 2331Zinc 2; via tele nitrogen; catalytic1 Publication
    Metal bindingi241 – 2411Zinc 2; via carbonyl oxygen; catalyticBy similarity
    Metal bindingi292 – 2921Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi294 – 2941Calcium 5; via carbonyl oxygenBy similarity
    Metal bindingi336 – 3361Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi338 – 3381Calcium 5; via carbonyl oxygenBy similarity
    Metal bindingi384 – 3841Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi386 – 3861Calcium 5; via carbonyl oxygenBy similarity
    Metal bindingi433 – 4331Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi435 – 4351Calcium 5; via carbonyl oxygenBy similarity

    GO - Molecular functioni

    1. calcium ion binding Source: UniProtKB
    2. collagen binding Source: UniProtKB
    3. metalloendopeptidase activity Source: MGI
    4. peptidase activity Source: MGI
    5. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. bone mineralization Source: UniProtKB
    2. bone morphogenesis Source: UniProtKB
    3. cartilage development Source: MGI
    4. cellular protein metabolic process Source: MGI
    5. collagen catabolic process Source: UniProtKB
    6. endochondral ossification Source: UniProtKB
    7. extracellular matrix disassembly Source: UniProtKB
    8. proteolysis Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Collagen degradation

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_199000. Activation of Matrix Metalloproteinases.
    REACT_199052. Degradation of the extracellular matrix.
    REACT_199055. Collagen degradation.

    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
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1340026. Mmp13.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Propeptidei20 – 10485Activation peptide1 PublicationPRO_0000028790Add
    BLAST
    Chaini105 – 472368Collagenase 3PRO_0000028791Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi118 – 1181N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi285 ↔ 472By similarity
    Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence Analysis

    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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PRIDEiP33435.

    PTM databases

    PhosphoSiteiP33435.

    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

    ArrayExpressiP33435.
    BgeeiP33435.
    CleanExiMM_MMP13.
    GenevestigatoriP33435.

    Structurei

    Secondary structure

    1
    472
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi117 – 1237
    Helixi132 – 14716
    Beta strandi153 – 1564
    Beta strandi158 – 1603
    Beta strandi163 – 1697
    Beta strandi174 – 1763
    Beta strandi181 – 1844
    Beta strandi187 – 1893
    Beta strandi192 – 1943
    Turni195 – 1984
    Beta strandi200 – 2034
    Beta strandi208 – 2169
    Helixi217 – 22913
    Beta strandi242 – 2443
    Helixi257 – 26711

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CXVX-ray2.00A/B105-268[»]
    ProteinModelPortaliP33435.
    SMRiP33435. Positions 36-472.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP33435.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati282 – 33150Hemopexin 1Add
    BLAST
    Repeati332 – 37847Hemopexin 2Add
    BLAST
    Repeati380 – 42849Hemopexin 3Add
    BLAST
    Repeati429 – 47244Hemopexin 4Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni177 – 24771Interaction with TIMP2By similarityAdd
    BLAST
    Regioni269 – 472204Interaction with collagenBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi95 – 1028Cysteine switchBy similarity

    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

    eggNOGiNOG299356.
    HOGENOMiHOG000217927.
    HOVERGENiHBG052484.
    InParanoidiP33435.
    KOiK07994.
    OMAiNQVWSYD.
    OrthoDBiEOG7XPZ57.
    PhylomeDBiP33435.
    TreeFamiTF315428.

    Family and domain databases

    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.
    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:SF130. PTHR10201:SF130. 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

    MHSAILATFF LLSWTPCWSL PLPYGDDDDD DLSEEDLVFA EHYLKSYYHP    50
    ATLAGILKKS TVTSTVDRLR EMQSFFGLEV TGKLDDPTLD IMRKPRCGVP 100
    DVGEYNVFPR TLKWSQTNLT YRIVNYTPDM SHSEVEKAFR KAFKVWSDVT 150
    PLNFTRIYDG TADIMISFGT KEHGDFYPFD GPSGLLAHAF PPGPNYGGDA 200
    HFDDDETWTS SSKGYNLFIV AAHELGHSLG LDHSKDPGAL MFPIYTYTGK 250
    SHFMLPDDDV QGIQFLYGPG DEDPNPKHPK TPEKCDPALS LDAITSLRGE 300
    TMIFKDRFFW RLHPQQVEAE LFLTKSFWPE LPNHVDAAYE HPSRDLMFIF 350
    RGRKFWALNG YDILEGYPRK ISDLGFPKEV KRLSAAVHFE NTGKTLFFSE 400
    NHVWSYDDVN QTMDKDYPRL IEEEFPGIGN KVDAVYEKNG YIYFFNGPIQ 450
    FEYSIWSNRI VRVMPTNSIL WC 472
    Length:472
    Mass (Da):54,182
    Last modified:February 1, 1994 - v1
    Checksum:i67F437B89B4D0DBD
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X66473 mRNA. Translation: CAA47102.1 .
    CCDSi CCDS22803.1.
    PIRi S29243.
    RefSeqi NP_032633.1. NM_008607.2.
    UniGenei Mm.5022.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CXV X-ray 2.00 A/B 105-268 [» ]
    ProteinModelPortali P33435.
    SMRi P33435. Positions 36-472.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi M10.013.

    PTM databases

    PhosphoSitei P33435.

    Proteomic databases

    PRIDEi P33435.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000015394 ; ENSMUSP00000015394 ; ENSMUSG00000050578 .
    GeneIDi 17386.
    KEGGi mmu:17386.
    UCSCi uc009ocg.2. mouse.

    Organism-specific databases

    CTDi 4322.
    MGIi MGI:1340026. Mmp13.

    Phylogenomic databases

    eggNOGi NOG299356.
    HOGENOMi HOG000217927.
    HOVERGENi HBG052484.
    InParanoidi P33435.
    KOi K07994.
    OMAi NQVWSYD.
    OrthoDBi EOG7XPZ57.
    PhylomeDBi P33435.
    TreeFami TF315428.

    Enzyme and pathway databases

    Reactomei REACT_199000. Activation of Matrix Metalloproteinases.
    REACT_199052. Degradation of the extracellular matrix.
    REACT_199055. Collagen degradation.

    Miscellaneous databases

    ChiTaRSi MMP13. mouse.
    EvolutionaryTracei P33435.
    NextBioi 291996.
    PROi P33435.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P33435.
    Bgeei P33435.
    CleanExi MM_MMP13.
    Genevestigatori P33435.

    Family and domain databases

    Gene3Di 2.110.10.10. 1 hit.
    3.40.390.10. 1 hit.
    InterProi IPR028711. 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 ]
    PANTHERi PTHR10201:SF130. PTHR10201:SF130. 1 hit.
    Pfami PF00045. Hemopexin. 4 hits.
    PF00413. Peptidase_M10. 1 hit.
    PF01471. PG_binding_1. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001191. Peptidase_M10A_matrix. 1 hit.
    PRINTSi PR00138. MATRIXIN.
    SMARTi SM00120. HX. 4 hits.
    SM00235. ZnMc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47090. SSF47090. 1 hit.
    SSF50923. SSF50923. 1 hit.
    PROSITEi PS00546. CYSTEINE_SWITCH. 1 hit.
    PS00024. HEMOPEXIN. 1 hit.
    PS51642. HEMOPEXIN_2. 4 hits.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-268 IN COMPLEX WITH ZINC AND CALCIUM IONS, COFACTOR.

    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: October 1, 2014
    This is version 135 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

    External Data

    Dasty 3