Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P45452

- MMP13_HUMAN

UniProt

P45452 - MMP13_HUMAN

Protein

Collagenase 3

Gene

MMP13

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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.12 Publications

    Cofactori

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

    Enzyme regulationi

    Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi96 – 961Zinc 2; in inhibited formBy similarity
    Metal bindingi128 – 1281Calcium 113 Publications
    Metal bindingi162 – 1621Calcium 2; via carbonyl oxygen13 Publications
    Metal bindingi172 – 1721Zinc 1; via tele nitrogen12 Publications
    Metal bindingi174 – 1741Zinc 112 Publications
    Metal bindingi179 – 1791Calcium 313 Publications
    Metal bindingi180 – 1801Calcium 3; via carbonyl oxygen13 Publications
    Metal bindingi182 – 1821Calcium 3; via carbonyl oxygen13 Publications
    Metal bindingi184 – 1841Calcium 3; via carbonyl oxygen13 Publications
    Metal bindingi187 – 1871Zinc 1; via tele nitrogen12 Publications
    Metal bindingi194 – 1941Calcium 2; via carbonyl oxygen13 Publications
    Metal bindingi196 – 1961Calcium 2; via carbonyl oxygen13 Publications
    Metal bindingi198 – 1981Calcium 213 Publications
    Metal bindingi200 – 2001Zinc 1; via pros nitrogen12 Publications
    Metal bindingi202 – 2021Calcium 313 Publications
    Metal bindingi203 – 2031Calcium 113 Publications
    Metal bindingi205 – 2051Calcium 1; via carbonyl oxygen13 Publications
    Metal bindingi205 – 2051Calcium 313 Publications
    Metal bindingi222 – 2221Zinc 2; via tele nitrogen; catalytic12 Publications
    Active sitei223 – 22311 Publication
    Metal bindingi226 – 2261Zinc 2; via tele nitrogen; catalytic12 Publications
    Metal bindingi232 – 2321Zinc 2; via tele nitrogen; catalytic12 Publications
    Metal bindingi240 – 2401Zinc 2; via carbonyl oxygen; catalytic12 Publications
    Metal bindingi291 – 2911Calcium 4; via carbonyl oxygen13 Publications
    Metal bindingi293 – 2931Calcium 5; via carbonyl oxygen13 Publications
    Metal bindingi335 – 3351Calcium 4; via carbonyl oxygen13 Publications
    Metal bindingi337 – 3371Calcium 5; via carbonyl oxygen13 Publications
    Metal bindingi383 – 3831Calcium 4; via carbonyl oxygen13 Publications
    Metal bindingi385 – 3851Calcium 5; via carbonyl oxygen13 Publications
    Metal bindingi432 – 4321Calcium 4; via carbonyl oxygen13 Publications
    Metal bindingi434 – 4341Calcium 5; via carbonyl oxygen13 Publications

    GO - Molecular functioni

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

    GO - Biological processi

    1. bone mineralization Source: Ensembl
    2. bone morphogenesis Source: UniProtKB
    3. cartilage development Source: Ensembl
    4. cellular protein metabolic process Source: Ensembl
    5. collagen catabolic process Source: UniProtKB
    6. extracellular matrix disassembly Source: UniProtKB
    7. extracellular matrix organization Source: Reactome
    8. proteolysis Source: ProtInc

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Collagen degradation

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_118572. Degradation of the extracellular matrix.
    REACT_118682. Activation of Matrix Metalloproteinases.
    REACT_150180. Assembly of collagen fibrils and other multimeric structures.
    REACT_150401. Collagen degradation.
    REACT_222620. 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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:7159. MMP13.

    Subcellular locationi

    Secretedextracellular spaceextracellular matrix 1 Publication. Secreted 1 Publication

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:602111]: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti75 – 751F → S in SEMD-MO; abnormal intracellular autoactivation and autodegradation within the ER/Golgi resulting in the secretion of small and inactive fragments. 1 Publication
    VAR_032753
    Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti74 – 741F → S in MANDP1. 1 Publication
    VAR_063432
    Natural varianti91 – 911M → T in MANDP1. 1 Publication
    VAR_063433
    Natural varianti232 – 2321H → N in MANDP1. 1 Publication
    VAR_063434

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi223 – 2231E → A: Abolishes enzyme activity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi602111. phenotype.
    Orphaneti1040. Metaphyseal anadysplasia.
    93356. Spondyloepimetaphyseal dysplasia, Missouri type.
    PharmGKBiPA30871.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 19191 PublicationAdd
    BLAST
    Propeptidei20 – 10384Activation peptide1 PublicationPRO_0000028788Add
    BLAST
    Chaini104 – 471368Collagenase 3PRO_0000028789Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi117 – 1171N-linked (GlcNAc...)1 Publication
    Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi284 ↔ 4712 Publications

    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).
    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiP45452.
    PRIDEiP45452.

    PTM databases

    PhosphoSiteiP45452.

    Miscellaneous databases

    PMAP-CutDBP45452.

    Expressioni

    Tissue specificityi

    Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue.4 Publications

    Inductioni

    Up-regulated by TNF and IL1B.2 Publications

    Gene expression databases

    ArrayExpressiP45452.
    BgeeiP45452.
    CleanExiHS_MMP13.
    GenevestigatoriP45452.

    Interactioni

    Subunit structurei

    Monomer. Interacts with TIMP1, TIMP2 and TIMP3. Binds (via the C-terminal region) to collagen.15 Publications

    Protein-protein interaction databases

    BioGridi110465. 1 interaction.
    STRINGi9606.ENSP00000260302.

    Structurei

    Secondary structure

    1
    471
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions