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P12032

- TIMP1_MOUSE

UniProt

P12032 - TIMP1_MOUSE

Protein

Metalloproteinase inhibitor 1

Gene

Timp1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 2 (01 May 1991)
      Previous versions | rss
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    Functioni

    Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14 By similarity. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi25 – 251Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

    GO - Molecular functioni

    1. cytokine activity Source: UniProtKB
    2. metal ion binding Source: UniProtKB-KW
    3. metalloendopeptidase inhibitor activity Source: UniProtKB

    GO - Biological processi

    1. aging Source: Ensembl
    2. cell activation Source: Ensembl
    3. negative regulation of apoptotic process Source: Ensembl
    4. negative regulation of endopeptidase activity Source: UniProtKB
    5. negative regulation of membrane protein ectodomain proteolysis Source: Ensembl
    6. negative regulation of metalloenzyme activity Source: UniProtKB
    7. negative regulation of trophoblast cell migration Source: Ensembl
    8. positive regulation of cell proliferation Source: UniProtKB
    9. regulation of integrin-mediated signaling pathway Source: UniProtKB
    10. response to cytokine Source: Ensembl
    11. response to peptide hormone Source: Ensembl
    12. wound healing Source: Ensembl

    Keywords - Molecular functioni

    Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_199000. Activation of Matrix Metalloproteinases.

    Protein family/group databases

    MEROPSiI35.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Metalloproteinase inhibitor 1
    Alternative name(s):
    Collagenase inhibitor 16C8 fibroblast
    Erythroid-potentiating activity
    Short name:
    EPA
    TPA-S1
    TPA-induced protein
    Tissue inhibitor of metalloproteinases 1
    Short name:
    TIMP-1
    Gene namesi
    Name:Timp1
    Synonyms:Timp, Timp-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:98752. Timp1.

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. basement membrane Source: MGI
    2. extracellular space Source: UniProtKB
    3. proteinaceous extracellular matrix Source: MGI

    Keywords - Cellular componenti

    Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Add
    BLAST
    Chaini25 – 205181Metalloproteinase inhibitor 1PRO_0000034325Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi25 ↔ 94PROSITE-ProRule annotation
    Disulfide bondi27 ↔ 123PROSITE-ProRule annotation
    Disulfide bondi37 ↔ 148PROSITE-ProRule annotation
    Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi102 – 1021N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi151 ↔ 197PROSITE-ProRule annotation
    Disulfide bondi156 ↔ 161PROSITE-ProRule annotation
    Disulfide bondi169 ↔ 189PROSITE-ProRule annotation

    Post-translational modificationi

    The activity of TIMP1 is dependent on the presence of disulfide bonds.By similarity
    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP12032.
    PRIDEiP12032.

    PTM databases

    PhosphoSiteiP12032.

    Expressioni

    Tissue specificityi

    Found in fetal and adult tissues. Highest levels are found in bone. Also found in lung, ovary and uterus.

    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

    Inductioni

    Regulated by tumor promoters and mitogens through protein kinase C. Also induced by viruses.

    Gene expression databases

    BgeeiP12032.
    CleanExiMM_TIMP1.
    GenevestigatoriP12032.

    Interactioni

    Subunit structurei

    Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14 By similarity. Interacts with CD63; identified in a complex with CD63 and ITGB1.By similarity1 Publication

    Protein-protein interaction databases

    MINTiMINT-4996416.
    STRINGi10090.ENSMUSP00000110999.

    Structurei

    3D structure databases

    ProteinModelPortaliP12032.
    SMRiP12032. Positions 25-202.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 148124NTRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni25 – 295Involved in metalloproteinase-bindingBy similarity
    Regioni91 – 922Involved in metalloproteinase-bindingBy similarity

    Sequence similaritiesi

    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG259409.
    GeneTreeiENSGT00390000004555.
    HOGENOMiHOG000285981.
    HOVERGENiHBG068749.
    InParanoidiP12032.
    KOiK16451.
    OMAiDKGFQSR.
    OrthoDBiEOG79GT74.
    PhylomeDBiP12032.
    TreeFamiTF317409.

    Family and domain databases

    Gene3Di3.90.370.10. 1 hit.
    InterProiIPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR015611. TIMP1.
    IPR027465. TIMP_C_dom.
    [Graphical view]
    PANTHERiPTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF20. PTHR11844:SF20. 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.

    P12032-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMAPFASLAS GILLLLSLIA SSKACSCAPP HPQTAFCNSD LVIRAKFMGS    50
    PEINETTLYQ RYKIKMTKML KGFKAVGNAA DIRYAYTPVM ESLCGYAHKS 100
    QNRSEEFLIT GRLRNGNLHI SACSFLVPWR TLSPAQQRAF SKTYSAGCGV 150
    CTVFPCLSIP CKLESDTHCL WTDQVLVGSE DYQSRHFACL PRNPGLCTWR 200
    SLGAR 205
    Length:205
    Mass (Da):22,628
    Last modified:May 1, 1991 - v2
    Checksum:iFACA952D49A50FD7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti52 – 521E → R in AAB42179. (PubMed:3034603)Curated
    Sequence conflicti66 – 661M → MM in AAB42179. (PubMed:3034603)Curated
    Sequence conflicti117 – 1182NL → KF in AAB42179. (PubMed:3034603)Curated
    Sequence conflicti121 – 1211S → N in AAB42179. (PubMed:3034603)Curated
    Sequence conflicti139 – 1391A → V(PubMed:3034603)Curated
    Sequence conflicti143 – 1431T → KN(PubMed:3034603)Curated
    Sequence conflicti194 – 1941P → L(PubMed:3034603)Curated
    Sequence conflicti194 – 1941P → L(PubMed:6179042)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M28312
    , M28308, M28309, M28310, M28311 Genomic DNA. Translation: AAB42179.1.
    X04684 mRNA. Translation: CAA28387.1.
    M17243 mRNA. Translation: AAA40471.1.
    BC008107 mRNA. Translation: AAH08107.1.
    BC034260 mRNA. Translation: AAH34260.1.
    BC051260 mRNA. Translation: AAH51260.1.
    V00755 mRNA. Translation: CAA24132.1.
    CCDSiCCDS30046.1.
    PIRiA26917. A26106.
    RefSeqiNP_001037849.1. NM_001044384.1.
    NP_035723.2. NM_011593.2.
    UniGeneiMm.8245.

    Genome annotation databases

    EnsembliENSMUST00000009530; ENSMUSP00000009530; ENSMUSG00000001131.
    ENSMUST00000115342; ENSMUSP00000110999; ENSMUSG00000001131.
    GeneIDi21857.
    KEGGimmu:21857.
    UCSCiuc009sty.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M28312
    , M28308 , M28309 , M28310 , M28311 Genomic DNA. Translation: AAB42179.1 .
    X04684 mRNA. Translation: CAA28387.1 .
    M17243 mRNA. Translation: AAA40471.1 .
    BC008107 mRNA. Translation: AAH08107.1 .
    BC034260 mRNA. Translation: AAH34260.1 .
    BC051260 mRNA. Translation: AAH51260.1 .
    V00755 mRNA. Translation: CAA24132.1 .
    CCDSi CCDS30046.1.
    PIRi A26917. A26106.
    RefSeqi NP_001037849.1. NM_001044384.1.
    NP_035723.2. NM_011593.2.
    UniGenei Mm.8245.

    3D structure databases

    ProteinModelPortali P12032.
    SMRi P12032. Positions 25-202.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4996416.
    STRINGi 10090.ENSMUSP00000110999.

    Protein family/group databases

    MEROPSi I35.001.

    PTM databases

    PhosphoSitei P12032.

    Proteomic databases

    PaxDbi P12032.
    PRIDEi P12032.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000009530 ; ENSMUSP00000009530 ; ENSMUSG00000001131 .
    ENSMUST00000115342 ; ENSMUSP00000110999 ; ENSMUSG00000001131 .
    GeneIDi 21857.
    KEGGi mmu:21857.
    UCSCi uc009sty.1. mouse.

    Organism-specific databases

    CTDi 7076.
    MGIi MGI:98752. Timp1.

    Phylogenomic databases

    eggNOGi NOG259409.
    GeneTreei ENSGT00390000004555.
    HOGENOMi HOG000285981.
    HOVERGENi HBG068749.
    InParanoidi P12032.
    KOi K16451.
    OMAi DKGFQSR.
    OrthoDBi EOG79GT74.
    PhylomeDBi P12032.
    TreeFami TF317409.

    Enzyme and pathway databases

    Reactomei REACT_199000. Activation of Matrix Metalloproteinases.

    Miscellaneous databases

    NextBioi 301350.
    PROi P12032.
    SOURCEi Search...

    Gene expression databases

    Bgeei P12032.
    CleanExi MM_TIMP1.
    Genevestigatori P12032.

    Family and domain databases

    Gene3Di 3.90.370.10. 1 hit.
    InterProi IPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR015611. TIMP1.
    IPR027465. TIMP_C_dom.
    [Graphical view ]
    PANTHERi PTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF20. PTHR11844:SF20. 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. "Characterization and expression of a murine gene homologous to human EPA/TIMP: a virus-induced gene in the mouse."
      Gewert D.R., Coulombe B., Castelino M., Skup D., Williams B.R.G.
      EMBO J. 6:651-657(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "A growth-responsive gene (16C8) in normal mouse fibroblasts homologous to a human collagenase inhibitor with erythroid-potentiating activity: evidence for inducible and constitutive transcripts."
      Edwards D.R., Waterhouse P., Holman M.L., Denhardt D.T.
      Nucleic Acids Res. 14:8863-8878(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fibroblast.
    3. "Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C."
      Johnson M.D., Housey G.M., Kirschmeier P.T., Weinstein I.B.
      Mol. Cell. Biol. 7:2821-2829(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C3H.
    4. "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].
      Strain: FVB/N.
      Tissue: Mammary gland and Osteoblast.
    5. "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: PARTIAL NUCLEOTIDE SEQUENCE, DEVELOPMENTAL STAGE.
      Tissue: Embryo.
    6. "Molecular cloning of partial cDNA copies of two distinct mouse IFN-beta mRNAs."
      Skup D., Windass J.D., Sor F.S., George H., Williams B.R., Fukuhara H., de Maeyer-Guignard J., de Maeyer E.
      Nucleic Acids Res. 10:3069-3084(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 168-205.
    7. "Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation."
      Toricelli M., Melo F.H., Peres G.B., Silva D.C., Jasiulionis M.G.
      Mol. Cancer 12:22-22(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CD63, IDENTIFICATION IN A COMPLEX WITH CD63 AND ITGB1.

    Entry informationi

    Entry nameiTIMP1_MOUSE
    AccessioniPrimary (citable) accession number: P12032
    Secondary accession number(s): P20064, Q61720
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: May 1, 1991
    Last modified: October 1, 2014
    This is version 137 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3