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P33436

- MMP2_RAT

UniProt

P33436 - MMP2_RAT

Protein

72 kDa type IV collagenase

Gene

Mmp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (01 May 2007)
      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/beta3 on the surface of blood vessels By similarity.By similarity

    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. fibronectin binding Source: RGD
    2. metalloendopeptidase activity Source: InterPro
    3. metallopeptidase activity Source: RGD
    4. peptidase activity Source: RGD
    5. zinc ion binding Source: InterPro

    GO - Biological processi

    1. anatomical structure regression Source: RGD
    2. angiogenesis Source: RGD
    3. cell migration Source: RGD
    4. cellular response to cytokine stimulus Source: RGD
    5. cellular response to estradiol stimulus Source: RGD
    6. cellular response to fluid shear stress Source: RGD
    7. cellular response to interleukin-1 Source: RGD
    8. collagen catabolic process Source: RGD
    9. female pregnancy Source: RGD
    10. luteinization Source: RGD
    11. negative regulation of cell adhesion Source: RGD
    12. negative regulation of vasoconstriction Source: RGD
    13. ovarian follicle development Source: RGD
    14. ovulation from ovarian follicle Source: RGD
    15. parturition Source: RGD
    16. peripheral nervous system axon regeneration Source: RGD
    17. positive regulation of apoptotic process Source: RGD
    18. positive regulation of cell migration Source: RGD
    19. prostate gland epithelium morphogenesis Source: RGD
    20. proteolysis Source: RGD
    21. response to activity Source: RGD
    22. response to cytokine Source: RGD
    23. response to drug Source: RGD
    24. response to electrical stimulus Source: RGD
    25. response to estrogen Source: RGD
    26. response to hydrogen peroxide Source: RGD
    27. response to hyperoxia Source: RGD
    28. response to hypoxia Source: RGD
    29. response to mechanical stimulus Source: RGD
    30. response to nicotine Source: RGD
    31. response to oxidative stress Source: RGD
    32. response to radiation Source: RGD
    33. response to retinoic acid Source: RGD
    34. tissue remodeling Source: RGD

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Angiogenesis, Collagen degradation

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi621316. Mmp2.

    Subcellular locationi

    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: RGD
    2. extracellular space Source: RGD
    3. membrane Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB-SubCell
    5. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Membrane, Nucleus, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2929Sequence AnalysisAdd
    BLAST
    Propeptidei30 – 10980Activation peptidePRO_0000028720Add
    BLAST
    Chaini110 – 66255372 kDa type IV collagenasePRO_0000028721Add
    BLAST
    Chaini445 – 662218PEXBy similarityPRO_0000391629Add
    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 integrin integrinv/beta3 By similarity.By similarity

    Keywords - PTMi

    Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

    Proteomic databases

    PaxDbiP33436.
    PRIDEiP33436.

    Expressioni

    Gene expression databases

    GenevestigatoriP33436.

    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

    Structurei

    3D structure databases

    ProteinModelPortaliP33436.
    SMRiP33436. 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.
    HOVERGENiHBG052484.
    KOiK01398.
    PhylomeDBiP33436.

    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]

    Sequencei

    Sequence statusi: Complete.

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

    P33436-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEARLVWGVL VGPLRVLCVL CCLLGHAIAA PSPIIKFPGD VSPKTDKELA    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 TMGGNGDGQP CKFPFRFQGT 300
    SYNSCTTEGR TDGYRWCGTT EDYDRDKKYG FCPETAMSTV GGNSEGAPCV 350
    FPFTFLGNKY ESCTSAGRSD GKVWCATTTN YDDDRKWGFC PDQGYSLFLV 400
    AAHEFGHAMG LEHSQDPGAL MAPIYTYTKN FRLSNDDIKG IQELYGPSPD 450
    ADTDTGTGPT PTLGPVTPEI CKQDIVFDGI AQIRGEIFFF KDRFIWRTVT 500
    PRDKPTGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWVYSASTL 550
    ERGYPKPLTS LGLPPDVQQV DAAFNWSKNK KTYIFSGDKF WRYNEVKKKM 600
    DPGFPKLIAD SWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV 650
    KFGSIKSDWL GC 662
    Length:662
    Mass (Da):74,149
    Last modified:May 1, 2007 - v2
    Checksum:iC56BD787473FC03E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti42 – 421S → A in CAA50583. (PubMed:7916617)Curated
    Sequence conflicti286 – 2861G → A in CAA50583. (PubMed:7916617)Curated
    Sequence conflicti369 – 3691S → N in CAA50583. (PubMed:7916617)Curated
    Sequence conflicti435 – 4351N → H in CAA50583. (PubMed:7916617)Curated
    Sequence conflicti586 – 5861S → A in CAA50583. (PubMed:7916617)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X71466 mRNA. Translation: CAA50583.1.
    U65656 mRNA. Translation: AAB41692.1.
    BC074013 mRNA. Translation: AAH74013.1.
    PIRiS34780.
    RefSeqiNP_112316.2. NM_031054.2.
    UniGeneiRn.6422.

    Genome annotation databases

    GeneIDi81686.
    KEGGirno:81686.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X71466 mRNA. Translation: CAA50583.1 .
    U65656 mRNA. Translation: AAB41692.1 .
    BC074013 mRNA. Translation: AAH74013.1 .
    PIRi S34780.
    RefSeqi NP_112316.2. NM_031054.2.
    UniGenei Rn.6422.

    3D structure databases

    ProteinModelPortali P33436.
    SMRi P33436. Positions 30-662.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P33436.
    ChEMBLi CHEMBL1075175.

    Protein family/group databases

    MEROPSi M10.003.

    Proteomic databases

    PaxDbi P33436.
    PRIDEi P33436.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 81686.
    KEGGi rno:81686.

    Organism-specific databases

    CTDi 4313.
    RGDi 621316. Mmp2.

    Phylogenomic databases

    eggNOGi NOG303159.
    HOVERGENi HBG052484.
    KOi K01398.
    PhylomeDBi P33436.

    Miscellaneous databases

    NextBioi 615320.
    PROi P33436.

    Gene expression databases

    Genevestigatori P33436.

    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. "Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells."
      Marti H.P., McNeil L., Davies M., Martin J., Lovett D.H.
      Biochem. J. 291:441-446(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The cloning of the cDNA encoding rat gelatinase A from a rat skin wound cDNA library."
      Okada A., Basset P.
      Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar.
      Tissue: Skin.
    3. "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].
      Tissue: Lung.

    Entry informationi

    Entry nameiMMP2_RAT
    AccessioniPrimary (citable) accession number: P33436
    Secondary accession number(s): P97581, Q6GMM9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: May 1, 2007
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 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. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3