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P30121

- TIMP2_RAT

UniProt

P30121 - TIMP2_RAT

Protein

Metalloproteinase inhibitor 2

Gene

Timp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 3 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi27 – 271Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

    GO - Molecular functioni

    1. enzyme activator activity Source: Ensembl
    2. integrin binding Source: RGD
    3. metal ion binding Source: UniProtKB-KW
    4. metalloendopeptidase inhibitor activity Source: RGD

    GO - Biological processi

    1. aging Source: RGD
    2. cellular response to organic substance Source: Ensembl
    3. central nervous system development Source: RGD
    4. negative regulation of cell proliferation Source: RGD
    5. negative regulation of endopeptidase activity Source: GOC
    6. negative regulation of mitotic cell cycle Source: RGD
    7. negative regulation of proteolysis Source: RGD
    8. negative regulation of Ras protein signal transduction Source: RGD
    9. positive regulation of adenylate cyclase activity Source: RGD
    10. positive regulation of MAPK cascade Source: RGD
    11. positive regulation of neuron differentiation Source: RGD
    12. regulation of Rap protein signal transduction Source: RGD
    13. response to cytokine Source: RGD
    14. response to drug Source: RGD
    15. spermatogenesis Source: RGD

    Keywords - Molecular functioni

    Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_198590. Activation of Matrix Metalloproteinases.

    Protein family/group databases

    MEROPSiI35.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Metalloproteinase inhibitor 2
    Alternative name(s):
    Tissue inhibitor of metalloproteinases 2
    Short name:
    TIMP-2
    Gene namesi
    Name:Timp2
    Synonyms:Timp-2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi61312. Timp2.

    Subcellular locationi

    GO - Cellular componenti

    1. basement membrane Source: Ensembl
    2. cell surface Source: RGD
    3. extracellular space Source: RGD
    4. growth cone Source: RGD
    5. neuronal cell body Source: RGD
    6. neuron projection Source: RGD

    Keywords - Cellular componenti

    Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 26261 PublicationAdd
    BLAST
    Chaini27 – 220194Metalloproteinase inhibitor 2PRO_0000034337Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi27 ↔ 98PROSITE-ProRule annotation
    Disulfide bondi29 ↔ 127PROSITE-ProRule annotation
    Disulfide bondi39 ↔ 152PROSITE-ProRule annotation
    Disulfide bondi154 ↔ 201PROSITE-ProRule annotation
    Disulfide bondi159 ↔ 164PROSITE-ProRule annotation
    Disulfide bondi172 ↔ 193PROSITE-ProRule annotation

    Post-translational modificationi

    The activity of TIMP2 is dependent on the presence of disulfide bonds.

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiP30121.

    Expressioni

    Gene expression databases

    GenevestigatoriP30121.

    Interactioni

    Subunit structurei

    Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000004290.

    Structurei

    3D structure databases

    ProteinModelPortaliP30121.
    SMRiP30121. Positions 27-208.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 152126NTRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni27 – 315Involved in metalloproteinase-bindingBy similarity
    Regioni95 – 962Involved in metalloproteinase-bindingBy similarity

    Sequence similaritiesi

    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG243625.
    GeneTreeiENSGT00390000004555.
    HOGENOMiHOG000285981.
    HOVERGENiHBG068749.
    OMAiSAPEECL.
    OrthoDBiEOG79GT74.
    PhylomeDBiP30121.

    Family and domain databases

    Gene3Di3.90.370.10. 1 hit.
    InterProiIPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR015613. TIMP2.
    IPR027465. TIMP_C_dom.
    [Graphical view]
    PANTHERiPTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF7. PTHR11844:SF7. 1 hit.
    PfamiPF00965. TIMP. 1 hit.
    [Graphical view]
    SMARTiSM00206. NTR. 1 hit.
    [Graphical view]
    SUPFAMiSSF50242. SSF50242. 1 hit.
    PROSITEiPS50189. NTR. 1 hit.
    PS00288. TIMP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P30121-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGAAARSLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV    50
    SEKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV 100
    SLDVGGKKEY LIAGKAEGDG KMHITLCDFI VPWDTLSITQ KKSLNHRYQM 150
    GCECKITRCP MIPCYISSPD ECLWMDWVTE KSINGHQAKF FACIKRSDGS 200
    CAWYRGAAPP KQEFLDIEDP 220
    Length:220
    Mass (Da):24,356
    Last modified:October 1, 1996 - v3
    Checksum:i1C97A3F050C3AE7D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti7 – 71S → T in AAA21553. (PubMed:8203893)Curated
    Sequence conflicti153 – 1531E → Q in AAA21553. (PubMed:8203893)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U14526 mRNA. Translation: AAA21553.1.
    L31884 mRNA. Translation: AAA84581.1.
    S72594 mRNA. Translation: AAC60687.1.
    S82718 mRNA. Translation: AAB49507.1.
    AJ409332 mRNA. Translation: CAC35060.1.
    BC084714 mRNA. Translation: AAH84714.1.
    PIRiS45683.
    RefSeqiNP_068824.1. NM_021989.2.
    UniGeneiRn.10161.

    Genome annotation databases

    EnsembliENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000003148.
    GeneIDi29543.
    KEGGirno:29543.
    UCSCiRGD:61312. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U14526 mRNA. Translation: AAA21553.1 .
    L31884 mRNA. Translation: AAA84581.1 .
    S72594 mRNA. Translation: AAC60687.1 .
    S82718 mRNA. Translation: AAB49507.1 .
    AJ409332 mRNA. Translation: CAC35060.1 .
    BC084714 mRNA. Translation: AAH84714.1 .
    PIRi S45683.
    RefSeqi NP_068824.1. NM_021989.2.
    UniGenei Rn.10161.

    3D structure databases

    ProteinModelPortali P30121.
    SMRi P30121. Positions 27-208.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000004290.

    Protein family/group databases

    MEROPSi I35.002.

    Proteomic databases

    PaxDbi P30121.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000004290 ; ENSRNOP00000004290 ; ENSRNOG00000003148 .
    GeneIDi 29543.
    KEGGi rno:29543.
    UCSCi RGD:61312. rat.

    Organism-specific databases

    CTDi 7077.
    RGDi 61312. Timp2.

    Phylogenomic databases

    eggNOGi NOG243625.
    GeneTreei ENSGT00390000004555.
    HOGENOMi HOG000285981.
    HOVERGENi HBG068749.
    OMAi SAPEECL.
    OrthoDBi EOG79GT74.
    PhylomeDBi P30121.

    Enzyme and pathway databases

    Reactomei REACT_198590. Activation of Matrix Metalloproteinases.

    Miscellaneous databases

    NextBioi 609549.
    PROi P30121.

    Gene expression databases

    Genevestigatori P30121.

    Family and domain databases

    Gene3Di 3.90.370.10. 1 hit.
    InterProi IPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR015613. TIMP2.
    IPR027465. TIMP_C_dom.
    [Graphical view ]
    PANTHERi PTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF7. PTHR11844:SF7. 1 hit.
    Pfami PF00965. TIMP. 1 hit.
    [Graphical view ]
    SMARTi SM00206. NTR. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50242. SSF50242. 1 hit.
    PROSITEi PS50189. NTR. 1 hit.
    PS00288. TIMP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells."
      Cook T.F., Burke J.S., Bergman K.D., Quinn C.O., Jeffrey J.J., Partridge N.C.
      Arch. Biochem. Biophys. 311:313-320(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Bone.
    2. Gibbons K.L., O'Grady R.L., Piper A.A.
      Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Mammary gland.
    3. "Cloning of the rat tissue inhibitor of metalloproteinases type 2 (TIMP-2) gene: analysis of its expression in normal and transformed thyroid cells."
      Santoro M., Battaglia C., Zhang L., Carlomagno F., Martelli M.L., Salvatore D., Fusco A.
      Exp. Cell Res. 213:398-403(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Purification, cDNA cloning, and developmental changes in the steady-state mRNA level of rat testicular tissue inhibitor of metalloproteases-2 (TIMP-2)."
      Grima J., Calcagno K., Cheng C.Y.
      J. Androl. 17:263-275(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Testis.
    5. "Cardiac remodeling after long term norepinephrine treatment in rats."
      Briest W., Hoelzl A., Rassler B., Deten A., Leicht M., Baba H.A., Zimmer H.G.
      Cardiovasc. Res. 52:265-273(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Heart.
    6. "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: Ovary.
    7. "Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases."
      Roswit W.T., McCourt D.W., Partridge N.C., Jeffrey J.J.
      Arch. Biochem. Biophys. 292:402-410(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 27-48.

    Entry informationi

    Entry nameiTIMP2_RAT
    AccessioniPrimary (citable) accession number: P30121
    Secondary accession number(s): Q546J4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 114 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3