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P39876

- TIMP3_MOUSE

UniProt

P39876 - TIMP3_MOUSE

Protein

Metalloproteinase inhibitor 3

Gene

Timp3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      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. May form part of a tissue-specific acute response to remodeling stimuli.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi24 – 241Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. cellular response to organic substance Source: MGI
    2. negative regulation of membrane protein ectodomain proteolysis Source: Ensembl

    Keywords - Molecular functioni

    Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiI35.003.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Metalloproteinase inhibitor 3
    Alternative name(s):
    Tissue inhibitor of metalloproteinases 3
    Short name:
    TIMP-3
    Gene namesi
    Name:Timp3
    Synonyms:Sun, Timp-3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:98754. Timp3.

    Subcellular locationi

    GO - Cellular componenti

    1. basement membrane Source: MGI

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 211188Metalloproteinase inhibitor 3PRO_0000034344Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi24 ↔ 91PROSITE-ProRule annotation
    Disulfide bondi26 ↔ 118PROSITE-ProRule annotation
    Disulfide bondi36 ↔ 143PROSITE-ProRule annotation
    Disulfide bondi145 ↔ 192PROSITE-ProRule annotation
    Disulfide bondi150 ↔ 155PROSITE-ProRule annotation
    Disulfide bondi163 ↔ 184PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    MaxQBiP39876.
    PaxDbiP39876.
    PRIDEiP39876.

    PTM databases

    PhosphoSiteiP39876.

    Expressioni

    Tissue specificityi

    Highest levels are found in kidney, lung and brain followed by ovary and uterus. Low levels are found in bone.

    Inductioni

    Highly induced by phorbol ester (PMA), EGF and transforming growth factor-beta 1. Also induced by dexamethasone.

    Gene expression databases

    ArrayExpressiP39876.
    BgeeiP39876.
    CleanExiMM_TIMP3.
    GenevestigatoriP39876.

    Interactioni

    Subunit structurei

    Interacts with EFEMP1.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP39876.
    SMRiP39876. Positions 24-199.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 143120NTRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni24 – 285Involved in metalloproteinase-bindingBy similarity
    Regioni88 – 892Involved in metalloproteinase-bindingBy similarity
    Regioni105 – 18884Mediates interaction with EFEMP1By similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG250837.
    HOGENOMiHOG000285981.
    HOVERGENiHBG068749.
    InParanoidiP39876.
    KOiK16866.
    OMAiKEGYCSW.
    OrthoDBiEOG79GT74.
    PhylomeDBiP39876.
    TreeFamiTF317409.

    Family and domain databases

    Gene3Di3.90.370.10. 1 hit.
    InterProiIPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR027465. TIMP_C_dom.
    IPR015612. Tissue_inhib_metalloprotease_3.
    [Graphical view]
    PANTHERiPTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF6. PTHR11844:SF6. 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.

    P39876-1 [UniParc]FASTAAdd to Basket

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    MTPWLGLVVL LSCWSLGHWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK    50
    LVKEGPFGTL VYTIKQMKMY RGFSKMPHVQ YIHTEASESL CGLKLEVNKY 100
    QYLLTGRVYE GKMYTGLCNF VERWDHLTLS QRKGLNYRYH LGCNCKIKSC 150
    YYLPCFVTSK NECLWTDMLS NFGYPGYQSK HYACIRQKGG YCSWYRGWAP 200
    PDKSISNATD P 211
    Length:211
    Mass (Da):24,182
    Last modified:February 1, 1995 - v1
    Checksum:i184EDF5B8D69B07B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti31 – 311P → S in AAH14713. (PubMed:15489334)Curated
    Sequence conflicti53 – 531K → T in AAH14713. (PubMed:15489334)Curated
    Sequence conflicti148 – 1481K → N in AAH14713. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27424 mRNA. Translation: AAA40447.1.
    Z30970 mRNA. Translation: CAA83218.1.
    L19622 mRNA. Translation: AAC37669.1.
    U26437
    , U26433, U26434, U26435, U26436 Genomic DNA. Translation: AAA85860.1.
    AK083905 mRNA. Translation: BAC39055.1.
    BC014713 mRNA. Translation: AAH14713.1.
    CCDSiCCDS24097.1.
    PIRiA53532.
    RefSeqiNP_035725.1. NM_011595.2.
    UniGeneiMm.4871.

    Genome annotation databases

    EnsembliENSMUST00000020234; ENSMUSP00000020234; ENSMUSG00000020044.
    GeneIDi21859.
    KEGGimmu:21859.
    UCSCiuc007gnr.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27424 mRNA. Translation: AAA40447.1 .
    Z30970 mRNA. Translation: CAA83218.1 .
    L19622 mRNA. Translation: AAC37669.1 .
    U26437
    , U26433 , U26434 , U26435 , U26436 Genomic DNA. Translation: AAA85860.1 .
    AK083905 mRNA. Translation: BAC39055.1 .
    BC014713 mRNA. Translation: AAH14713.1 .
    CCDSi CCDS24097.1.
    PIRi A53532.
    RefSeqi NP_035725.1. NM_011595.2.
    UniGenei Mm.4871.

    3D structure databases

    ProteinModelPortali P39876.
    SMRi P39876. Positions 24-199.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi I35.003.

    PTM databases

    PhosphoSitei P39876.

    Proteomic databases

    MaxQBi P39876.
    PaxDbi P39876.
    PRIDEi P39876.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000020234 ; ENSMUSP00000020234 ; ENSMUSG00000020044 .
    GeneIDi 21859.
    KEGGi mmu:21859.
    UCSCi uc007gnr.1. mouse.

    Organism-specific databases

    CTDi 7078.
    MGIi MGI:98754. Timp3.

    Phylogenomic databases

    eggNOGi NOG250837.
    HOGENOMi HOG000285981.
    HOVERGENi HBG068749.
    InParanoidi P39876.
    KOi K16866.
    OMAi KEGYCSW.
    OrthoDBi EOG79GT74.
    PhylomeDBi P39876.
    TreeFami TF317409.

    Miscellaneous databases

    NextBioi 301360.
    PROi P39876.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P39876.
    Bgeei P39876.
    CleanExi MM_TIMP3.
    Genevestigatori P39876.

    Family and domain databases

    Gene3Di 3.90.370.10. 1 hit.
    InterProi IPR001134. Netrin_domain.
    IPR001820. Prot_inh_TIMP.
    IPR008993. TIMP-like_OB-fold.
    IPR027465. TIMP_C_dom.
    IPR015612. Tissue_inhib_metalloprotease_3.
    [Graphical view ]
    PANTHERi PTHR11844. PTHR11844. 1 hit.
    PTHR11844:SF6. PTHR11844:SF6. 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. "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues."
      Leco K.J., Khokha R., Pavloff N., Hawkes S.P., Edwards D.R.
      J. Biol. Chem. 269:9352-9360(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Molecular cloning of five messenger RNAs differentially expressed in preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to human tissue inhibitor of metalloproteinases-3."
      Sun Y., Hegamyer G., Colburn N.H.
      Cancer Res. 54:1139-1144(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE.
      Strain: BALB/c.
      Tissue: Lung and Skin.
    3. "Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10."
      Apte S.S., Hayashi K., Seldin M.F., Mattei M.-G., Hayashi M., Olsen B.R.
      Dev. Dyn. 200:177-197(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lung.
    4. "Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered gene methylation."
      Sun Y., Hegamyer G., Kim H., Sithanandam K., Li H., Watts R., Colburn N.H.
      J. Biol. Chem. 270:19312-19319(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family."
      Apte S.S., Olsen B.R., Murphy G.
      J. Biol. Chem. 270:14313-14318(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/Sv.
    6. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Spinal ganglion.
    7. "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: Kidney.

    Entry informationi

    Entry nameiTIMP3_MOUSE
    AccessioniPrimary (citable) accession number: P39876
    Secondary accession number(s): Q91WL9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 124 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3