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P33434

- MMP2_MOUSE

UniProt

P33434 - MMP2_MOUSE

Protein

72 kDa type IV collagenase

Gene

Mmp2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 Feb 1994)
      Previous versions | rss
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    Functioni

    Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues By similarity.By similarity
    PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-v/beta-3 on the surface of blood vessels By similarity.By similarity
    Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.1 Publication

    Catalytic activityi

    Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.

    Cofactori

    Binds 4 calcium ions per subunit.By similarity
    Binds 2 zinc ions per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi102 – 1021Zinc 2; in inhibited formBy similarity
    Metal bindingi134 – 1341Calcium 1By similarity
    Metal bindingi168 – 1681Calcium 2By similarity
    Metal bindingi178 – 1781Zinc 1By similarity
    Metal bindingi180 – 1801Zinc 1By similarity
    Metal bindingi185 – 1851Calcium 3By similarity
    Metal bindingi186 – 1861Calcium 3; via carbonyl oxygenBy similarity
    Metal bindingi193 – 1931Zinc 1By similarity
    Metal bindingi200 – 2001Calcium 2; via carbonyl oxygenBy similarity
    Metal bindingi202 – 2021Calcium 2; via carbonyl oxygenBy similarity
    Metal bindingi204 – 2041Calcium 2By similarity
    Metal bindingi206 – 2061Zinc 1By similarity
    Metal bindingi208 – 2081Calcium 3By similarity
    Metal bindingi209 – 2091Calcium 1By similarity
    Metal bindingi211 – 2111Calcium 3By similarity
    Metal bindingi403 – 4031Zinc 2; catalyticBy similarity
    Active sitei404 – 4041PROSITE-ProRule annotation
    Metal bindingi407 – 4071Zinc 2; catalyticBy similarity
    Metal bindingi413 – 4131Zinc 2; catalyticBy similarity
    Metal bindingi478 – 4781Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi523 – 5231Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi571 – 5711Calcium 4; via carbonyl oxygenBy similarity
    Metal bindingi620 – 6201Calcium 4; via carbonyl oxygenBy similarity

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: MGI
    2. zinc ion binding Source: InterPro

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. blood vessel maturation Source: MGI
    3. bone trabecula formation Source: MGI
    4. cellular response to amino acid stimulus Source: MGI
    5. collagen catabolic process Source: MGI
    6. embryo implantation Source: MGI
    7. face morphogenesis Source: MGI
    8. intramembranous ossification Source: MGI
    9. positive regulation of innate immune response Source: MGI
    10. response to hypoxia Source: MGI
    11. skeletal system morphogenesis Source: MGI

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Angiogenesis, 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

    MEROPSiM10.003.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    72 kDa type IV collagenase (EC:3.4.24.24)
    Alternative name(s):
    72 kDa gelatinase
    Gelatinase A
    Matrix metalloproteinase-2
    Short name:
    MMP-2
    Cleaved into the following chain:
    Gene namesi
    Name:Mmp2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:97009. Mmp2.

    Subcellular locationi

    Isoform 1 : Secretedextracellular spaceextracellular matrix By similarity. Membrane By similarity. Nucleus By similarity
    Note: Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. extracellular space Source: MGI
    3. mitochondrion Source: MGI
    4. nucleus Source: UniProtKB-SubCell
    5. plasma membrane Source: MGI
    6. proteinaceous extracellular matrix Source: UniProtKB-SubCell
    7. sarcomere Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Extracellular matrix, Membrane, Mitochondrion, Nucleus, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2929Sequence AnalysisAdd
    BLAST
    Propeptidei30 – 10980Activation peptidePRO_0000028716Add
    BLAST
    Chaini110 – 66255372 kDa type IV collagenasePRO_0000028717Add
    BLAST
    Chaini445 – 662218PEXBy similarityPRO_0000391627Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi233 ↔ 259PROSITE-ProRule annotation
    Disulfide bondi247 ↔ 274PROSITE-ProRule annotation
    Disulfide bondi291 ↔ 317PROSITE-ProRule annotation
    Disulfide bondi305 ↔ 332PROSITE-ProRule annotation
    Disulfide bondi349 ↔ 375PROSITE-ProRule annotation
    Disulfide bondi363 ↔ 390PROSITE-ProRule annotation
    Disulfide bondi471 ↔ 662PROSITE-ProRule annotation
    Glycosylationi575 – 5751N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi644 – 6441N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro By similarity.By similarity
    The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3) By similarity. Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3 By similarity.By similarity

    Keywords - PTMi

    Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

    Proteomic databases

    PaxDbiP33434.
    PRIDEiP33434.

    PTM databases

    PhosphoSiteiP33434.

    Expressioni

    Developmental stagei

    Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.1 Publication

    Gene expression databases

    ArrayExpressiP33434.
    BgeeiP33434.
    CleanExiMM_MMP2.
    GenevestigatoriP33434.

    Interactioni

    Subunit structurei

    Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B By similarity.By similarity

    Protein-protein interaction databases

    IntActiP33434. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliP33434.
    SMRiP33434. Positions 30-662.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini228 – 27649Fibronectin type-II 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini286 – 33449Fibronectin type-II 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini344 – 39249Fibronectin type-II 3PROSITE-ProRule annotationAdd
    BLAST
    Repeati474 – 51845Hemopexin 1Add
    BLAST
    Repeati519 – 56547Hemopexin 2Add
    BLAST
    Repeati567 – 61549Hemopexin 3Add
    BLAST
    Repeati616 – 66247Hemopexin 4Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni110 – 221112Collagenase-like 1Add
    BLAST
    Regioni222 – 396175Collagen-bindingAdd
    BLAST
    Regioni397 – 46771Collagenase-like 2Add
    BLAST
    Regioni414 – 662249Required for inhibitor TIMP2 bindingBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi100 – 1078Cysteine 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.

    Sequence similaritiesi

    Belongs to the peptidase M10A family.Curated
    Contains 3 fibronectin type-II domains.PROSITE-ProRule annotation
    Contains 4 hemopexin repeats.Curated

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG303159.
    HOGENOMiHOG000217926.
    HOVERGENiHBG052484.
    InParanoidiP33434.
    KOiK01398.
    OMAiPCKFPFR.
    OrthoDBiEOG70KGNX.
    PhylomeDBiP33434.
    TreeFamiTF315428.

    Family and domain databases

    Gene3Di1.10.101.10. 1 hit.
    2.10.10.10. 3 hits.
    2.110.10.10. 1 hit.
    3.40.390.10. 2 hits.
    InterProiIPR028708. 72kDa_collagenase.
    IPR000562. FN_type2_col-bd.
    IPR000585. Hemopexin-like_dom.
    IPR018487. Hemopexin-like_repeat.
    IPR018486. Hemopexin_CS.
    IPR013806. Kringle-like.
    IPR024079. MetalloPept_cat_dom.
    IPR001818. Pept_M10_metallopeptidase.
    IPR021190. Pept_M10A.
    IPR021158. Pept_M10A_Zn_BS.
    IPR006026. Peptidase_Metallo.
    IPR002477. Peptidoglycan-bd-like.
    [Graphical view]
    PANTHERiPTHR10201:SF29. PTHR10201:SF29. 1 hit.
    PfamiPF00040. fn2. 3 hits.
    PF00045. Hemopexin. 4 hits.
    PF00413. Peptidase_M10. 1 hit.
    PF01471. PG_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00138. MATRIXIN.
    SMARTiSM00059. FN2. 3 hits.
    SM00120. HX. 4 hits.
    SM00235. ZnMc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47090. SSF47090. 1 hit.
    SSF50923. SSF50923. 1 hit.
    SSF57440. SSF57440. 3 hits.
    PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
    PS00023. FN2_1. 3 hits.
    PS51092. FN2_2. 3 hits.
    PS00024. HEMOPEXIN. 1 hit.
    PS51642. HEMOPEXIN_2. 4 hits.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P33434-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MEARVAWGAL AGPLRVLCVL CCLLGRAIAA PSPIIKFPGD VAPKTDKELA    50
    VQYLNTFYGC PKESCNLFVL KDTLKKMQKF FGLPQTGDLD QNTIETMRKP 100
    RCGNPDVANY NFFPRKPKWD KNQITYRIIG YTPDLDPETV DDAFARALKV 150
    WSDVTPLRFS RIHDGEADIM INFGRWEHGD GYPFDGKDGL LAHAFAPGTG 200
    VGGDSHFDDD ELWTLGEGQV VRVKYGNADG EYCKFPFLFN GREYSSCTDT 250
    GRSDGFLWCS TTYNFEKDGK YGFCPHEALF TMGGNADGQP CKFPFRFQGT 300
    SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV 350
    FPFTFLGNKY ESCTSAGRND GKVWCATTTN YDDDRKWGFC PDQGYSLFLV 400
    AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSHDDIKG IQELYGPSPD 450
    ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI AQIRGEIFFF KDRFIWRTVT 500
    PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL 550
    ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM 600
    DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV 650
    KFGSIKSDWL GC 662
    Length:662
    Mass (Da):74,102
    Last modified:February 1, 1994 - v1
    Checksum:iC630A7DBDB272F02
    GO
    Isoform 2 (identifier: P33434-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-76: Missing.

    Note: Induced by oxidative stress.

    Show »
    Length:586
    Mass (Da):65,883
    Checksum:iB8EE47CF5723C3D6
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7676Missing in isoform 2. CuratedVSP_044632Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84324 mRNA. Translation: AAA39338.1.
    BC070430 mRNA. Translation: AAH70430.1.
    CCDSiCCDS22523.1. [P33434-1]
    PIRiA42496.
    RefSeqiNP_032636.1. NM_008610.2. [P33434-1]
    UniGeneiMm.29564.

    Genome annotation databases

    EnsembliENSMUST00000034187; ENSMUSP00000034187; ENSMUSG00000031740. [P33434-1]
    GeneIDi17390.
    KEGGimmu:17390.
    UCSCiuc009mue.1. mouse. [P33434-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84324 mRNA. Translation: AAA39338.1 .
    BC070430 mRNA. Translation: AAH70430.1 .
    CCDSi CCDS22523.1. [P33434-1 ]
    PIRi A42496.
    RefSeqi NP_032636.1. NM_008610.2. [P33434-1 ]
    UniGenei Mm.29564.

    3D structure databases

    ProteinModelPortali P33434.
    SMRi P33434. Positions 30-662.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P33434. 1 interaction.

    Chemistry

    BindingDBi P33434.
    ChEMBLi CHEMBL3095.

    Protein family/group databases

    MEROPSi M10.003.

    PTM databases

    PhosphoSitei P33434.

    Proteomic databases

    PaxDbi P33434.
    PRIDEi P33434.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000034187 ; ENSMUSP00000034187 ; ENSMUSG00000031740 . [P33434-1 ]
    GeneIDi 17390.
    KEGGi mmu:17390.
    UCSCi uc009mue.1. mouse. [P33434-1 ]

    Organism-specific databases

    CTDi 4313.
    MGIi MGI:97009. Mmp2.

    Phylogenomic databases

    eggNOGi NOG303159.
    HOGENOMi HOG000217926.
    HOVERGENi HBG052484.
    InParanoidi P33434.
    KOi K01398.
    OMAi PCKFPFR.
    OrthoDBi EOG70KGNX.
    PhylomeDBi P33434.
    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 MMP2. mouse.
    NextBioi 292012.
    PROi P33434.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P33434.
    Bgeei P33434.
    CleanExi MM_MMP2.
    Genevestigatori P33434.

    Family and domain databases

    Gene3Di 1.10.101.10. 1 hit.
    2.10.10.10. 3 hits.
    2.110.10.10. 1 hit.
    3.40.390.10. 2 hits.
    InterProi IPR028708. 72kDa_collagenase.
    IPR000562. FN_type2_col-bd.
    IPR000585. Hemopexin-like_dom.
    IPR018487. Hemopexin-like_repeat.
    IPR018486. Hemopexin_CS.
    IPR013806. Kringle-like.
    IPR024079. MetalloPept_cat_dom.
    IPR001818. Pept_M10_metallopeptidase.
    IPR021190. Pept_M10A.
    IPR021158. Pept_M10A_Zn_BS.
    IPR006026. Peptidase_Metallo.
    IPR002477. Peptidoglycan-bd-like.
    [Graphical view ]
    PANTHERi PTHR10201:SF29. PTHR10201:SF29. 1 hit.
    Pfami PF00040. fn2. 3 hits.
    PF00045. Hemopexin. 4 hits.
    PF00413. Peptidase_M10. 1 hit.
    PF01471. PG_binding_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00138. MATRIXIN.
    SMARTi SM00059. FN2. 3 hits.
    SM00120. HX. 4 hits.
    SM00235. ZnMc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47090. SSF47090. 1 hit.
    SSF50923. SSF50923. 1 hit.
    SSF57440. SSF57440. 3 hits.
    PROSITEi PS00546. CYSTEINE_SWITCH. 1 hit.
    PS00023. FN2_1. 3 hits.
    PS51092. FN2_2. 3 hits.
    PS00024. HEMOPEXIN. 1 hit.
    PS51642. HEMOPEXIN_2. 4 hits.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of murine 72-kDa type IV collagenase and its expression during mouse development."
      Reponen P., Sahlberg C., Huhtala P., Hurskainen T., Thesleff I., Tryggvason K.
      J. Biol. Chem. 267:7856-7862(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "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] (ISOFORM 1).
      Strain: C57BL/6.
      Tissue: Brain.
    3. "Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development."
      Brenner C.A., Adler R.R., Rappolee D.A., Pedersen R.A., Werb Z.
      Genes Dev. 3:848-859(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.
      Tissue: Embryo.
    4. "A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity."
      Lovett D.H., Mahimkar R., Raffai R.L., Cape L., Maklashina E., Cecchini G., Karliner J.S.
      PLoS ONE 7:E34177-E34177(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiMMP2_MOUSE
    AccessioniPrimary (citable) accession number: P33434
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: October 1, 2014
    This is version 141 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

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3