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P78543

- BTG2_HUMAN

UniProt

P78543 - BTG2_HUMAN

Protein

Protein BTG2

Gene

BTG2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex. Activates mRNA deadenyltion in a CNOT6 and CNOT7-dependent manner. In vitro can inhibit deadenylase activity of CNOT7 and CNOT8. Involved in cell cycle regulation. Could be involved in the growth arrest and differentiation of the neuronal precursors By similarity. Modulates transcription regulation mediated by ESR1. Involved in mitochondrial depolarization and neurite outgrowth.By similarity5 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl

    GO - Biological processi

    1. anterior/posterior pattern specification Source: Ensembl
    2. associative learning Source: Ensembl
    3. cellular response to DNA damage stimulus Source: MGI
    4. central nervous system neuron development Source: Ensembl
    5. dentate gyrus development Source: Ensembl
    6. DNA repair Source: ProtInc
    7. negative regulation of cell proliferation Source: UniProtKB
    8. negative regulation of neural precursor cell proliferation Source: Ensembl
    9. negative regulation of neuron apoptotic process Source: Ensembl
    10. negative regulation of translation Source: UniProtKB
    11. neuron projection development Source: UniProtKB
    12. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: MGI
    13. protein methylation Source: Ensembl
    14. response to electrical stimulus Source: Ensembl
    15. response to mechanical stimulus Source: Ensembl
    16. response to organic cyclic compound Source: Ensembl
    17. response to peptide hormone Source: Ensembl
    18. skeletal muscle cell differentiation Source: Ensembl

    Keywords - Biological processi

    Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein BTG2
    Alternative name(s):
    BTG family member 2
    NGF-inducible anti-proliferative protein PC3
    Gene namesi
    Name:BTG2
    Synonyms:PC3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:1131. BTG2.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi53 – 531H → A: Impairs interaction with CNOT7 and CNOT8. 1 Publication
    Mutagenesisi65 – 651Y → A: Abolishes interaction with CNOT7 and CNOT8. 2 Publications
    Mutagenesisi75 – 751D → A: Abolishes interaction with CNOT7 and CNOT8. 1 Publication
    Mutagenesisi103 – 1031W → A: Abolishes interaction with CNOT7 and CNOT8; impairs anti-proliferative activity. 2 Publications
    Mutagenesisi105 – 1051D → A: Impairs interaction with CNOT7 and CNOT8. 1 Publication
    Mutagenesisi115 – 1151E → A: Impairs interaction with CNOT7. Inhibits CNOT7 mRNA deadenylase activity. 1 Publication
    Mutagenesisi147 – 1471S → A: Impairs phosphorylation by MAPK1 and MAPK3, and decreases PIN1-binding. 1 Publication
    Mutagenesisi148 – 1481P → A: Impairs PIN1-binding. 1 Publication
    Mutagenesisi149 – 1491S → A: Impairs phosphorylation by MAPK14, and decreases PIN1-binding. 1 Publication

    Organism-specific databases

    PharmGKBiPA25451.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 158158Protein BTG2PRO_0000143804Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei147 – 1471Phosphoserine; by MAPK1 and MAPK31 Publication
    Modified residuei149 – 1491Phosphoserine; by MAPK141 Publication

    Post-translational modificationi

    Phosphorylated at Ser-147 by MAPK1/ERK2 and MAPK3/ERK1, and at Ser-149 by MAPK14, leading to PIN1-binding and mitochondrial depolarization.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP78543.
    PRIDEiP78543.

    PTM databases

    PhosphoSiteiP78543.

    Expressioni

    Gene expression databases

    BgeeiP78543.
    CleanExiHS_BTG2.
    GenevestigatoriP78543.

    Organism-specific databases

    HPAiHPA002355.

    Interactioni

    Subunit structurei

    Interacts with PRKCABP By similarity. Interacts with CNOT7 and CNOT8; indicative for an asscociation with the CCR4-NOT complex. Interacts with PIN1, inducing mitochondrial depolarization.By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARP102754EBI-1047576,EBI-608057
    CNOT7Q9UIV12EBI-1047576,EBI-2105113
    Cnot7Q608095EBI-1047576,EBI-2104739From a different organism.
    CNOT8Q9UFF92EBI-1047576,EBI-742299

    Protein-protein interaction databases

    BioGridi113593. 20 interactions.
    IntActiP78543. 5 interactions.
    MINTiMINT-155716.
    STRINGi9606.ENSP00000290551.

    Structurei

    Secondary structure

    1
    158
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi10 – 2718
    Helixi32 – 5019
    Turni59 – 624
    Helixi63 – 664
    Beta strandi71 – 733
    Helixi76 – 849
    Helixi89 – 957
    Beta strandi100 – 1056
    Beta strandi108 – 1147
    Beta strandi119 – 1246

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3DJUX-ray2.26B7-128[»]
    3E9VX-ray1.70A8-127[»]
    ProteinModelPortaliP78543.
    SMRiP78543. Positions 8-127.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP78543.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the BTG family.Curated

    Phylogenomic databases

    eggNOGiNOG287298.
    HOGENOMiHOG000290200.
    HOVERGENiHBG004907.
    InParanoidiP78543.
    KOiK14443.
    OMAiPSKNYIM.
    OrthoDBiEOG72RN0S.
    PhylomeDBiP78543.
    TreeFamiTF105272.

    Family and domain databases

    InterProiIPR002087. Anti_prolifrtn.
    [Graphical view]
    PfamiPF07742. BTG. 1 hit.
    [Graphical view]
    PRINTSiPR00310. ANTIPRLFBTG1.
    SMARTiSM00099. btg1. 1 hit.
    [Graphical view]
    PROSITEiPS00960. BTG_1. 1 hit.
    PS01203. BTG_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P78543-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSHGKGTDML PEIAAAVGFL SSLLRTRGCV SEQRLKVFSG ALQEALTEHY    50
    KHHWFPEKPS KGSGYRCIRI NHKMDPIISR VASQIGLSQP QLHQLLPSEL 100
    TLWVDPYEVS YRIGEDGSIC VLYEEAPLAA SCGLLTCKNQ VLLGRSSPSK 150
    NYVMAVSS 158
    Length:158
    Mass (Da):17,416
    Last modified:May 1, 1997 - v1
    Checksum:iFFAA1844CC360209
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti153 – 1531V → M.
    Corresponds to variant rs12039961 [ dbSNP | Ensembl ].
    VAR_048437

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U72649 mRNA. Translation: AAB37580.1.
    Y09943 mRNA. Translation: CAA71074.1.
    AF361937 Genomic DNA. Translation: AAL05626.1.
    AL513326 Genomic DNA. Translation: CAH70451.1.
    CH471067 Genomic DNA. Translation: EAW91475.1.
    CH471067 Genomic DNA. Translation: EAW91476.1.
    BC105948 mRNA. Translation: AAI05949.1.
    BC105949 mRNA. Translation: AAI05950.1.
    CCDSiCCDS1437.1.
    RefSeqiNP_006754.1. NM_006763.2.
    UniGeneiHs.519162.

    Genome annotation databases

    EnsembliENST00000290551; ENSP00000290551; ENSG00000159388.
    ENST00000475157; ENSP00000433553; ENSG00000159388.
    GeneIDi7832.
    KEGGihsa:7832.
    UCSCiuc001gzq.3. human.

    Polymorphism databases

    DMDMi3023409.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U72649 mRNA. Translation: AAB37580.1 .
    Y09943 mRNA. Translation: CAA71074.1 .
    AF361937 Genomic DNA. Translation: AAL05626.1 .
    AL513326 Genomic DNA. Translation: CAH70451.1 .
    CH471067 Genomic DNA. Translation: EAW91475.1 .
    CH471067 Genomic DNA. Translation: EAW91476.1 .
    BC105948 mRNA. Translation: AAI05949.1 .
    BC105949 mRNA. Translation: AAI05950.1 .
    CCDSi CCDS1437.1.
    RefSeqi NP_006754.1. NM_006763.2.
    UniGenei Hs.519162.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3DJU X-ray 2.26 B 7-128 [» ]
    3E9V X-ray 1.70 A 8-127 [» ]
    ProteinModelPortali P78543.
    SMRi P78543. Positions 8-127.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113593. 20 interactions.
    IntActi P78543. 5 interactions.
    MINTi MINT-155716.
    STRINGi 9606.ENSP00000290551.

    PTM databases

    PhosphoSitei P78543.

    Polymorphism databases

    DMDMi 3023409.

    Proteomic databases

    PaxDbi P78543.
    PRIDEi P78543.

    Protocols and materials databases

    DNASUi 7832.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000290551 ; ENSP00000290551 ; ENSG00000159388 .
    ENST00000475157 ; ENSP00000433553 ; ENSG00000159388 .
    GeneIDi 7832.
    KEGGi hsa:7832.
    UCSCi uc001gzq.3. human.

    Organism-specific databases

    CTDi 7832.
    GeneCardsi GC01P203274.
    HGNCi HGNC:1131. BTG2.
    HPAi HPA002355.
    MIMi 601597. gene.
    neXtProti NX_P78543.
    PharmGKBi PA25451.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG287298.
    HOGENOMi HOG000290200.
    HOVERGENi HBG004907.
    InParanoidi P78543.
    KOi K14443.
    OMAi PSKNYIM.
    OrthoDBi EOG72RN0S.
    PhylomeDBi P78543.
    TreeFami TF105272.

    Miscellaneous databases

    EvolutionaryTracei P78543.
    GeneWikii BTG2.
    GenomeRNAii 7832.
    NextBioi 30230.
    PROi P78543.
    SOURCEi Search...

    Gene expression databases

    Bgeei P78543.
    CleanExi HS_BTG2.
    Genevestigatori P78543.

    Family and domain databases

    InterProi IPR002087. Anti_prolifrtn.
    [Graphical view ]
    Pfami PF07742. BTG. 1 hit.
    [Graphical view ]
    PRINTSi PR00310. ANTIPRLFBTG1.
    SMARTi SM00099. btg1. 1 hit.
    [Graphical view ]
    PROSITEi PS00960. BTG_1. 1 hit.
    PS01203. BTG_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway."
      Rouault J.-P., Falette N., Guehenneux F., Guillot C., Rimokh R., Wang Q., Berthet C., Moyret-Lalle C., Savatier P., Pain B., Shaw P., Berger R., Samarut J., Magaud J.-P., Ozturk M., Samarut C., Puisieux A.
      Nat. Genet. 14:482-486(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair?"
      Tirone F.
      J. Cell. Physiol. 187:155-165(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal liver.
    3. "The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene."
      Duriez C., Falette N., Audoynaud C., Moyret-Lalle C., Bensaad K., Courtois S., Wang Q., Soussi T., Puisieux A.
      Gene 282:207-214(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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].
    7. "Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex."
      Rouault J.P., Prevot D., Berthet C., Birot A.M., Billaud M., Magaud J.P., Corbo L.
      J. Biol. Chem. 273:22563-22569(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CNOT7.
    8. "Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway."
      Prevot D., Morel A.P., Voeltzel T., Rostan M.C., Rimokh R., Magaud J.P., Corbo L.
      J. Biol. Chem. 276:9640-9648(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CNOT8.
    9. "BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms."
      Morel A.-P., Sentis S., Bianchin C., Le Romancer M., Jonard L., Rostan M.-C., Rimokh R., Corbo L.
      J. Cell Sci. 116:2929-2936(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH THE CCR4-NOT COMPLEX.
    10. "Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1 binding in cytoplasm and cell death."
      Hong J.W., Ryu M.S., Lim I.K.
      J. Biol. Chem. 280:21256-21263(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-147 AND SER-149, MUTAGENESIS OF SER-147; PRO-148 AND SER-149, INTERACTION WITH PIN1, FUNCTION.
    11. "The BTG2 protein is a general activator of mRNA deadenylation."
      Mauxion F., Faux C., Seraphin B.
      EMBO J. 27:1039-1048(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "PRMT1 and Btg2 regulates neurite outgrowth of Neuro2a cells."
      Miyata S., Mori Y., Tohyama M.
      Neurosci. Lett. 445:162-165(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex."
      Doidge R., Mittal S., Aslam A., Winkler G.S.
      PLoS ONE 7:E51331-E51331(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CNOT7 AND CNOT8, MUTAGENESIS OF HIS-53; TYR-65; ASP-75; TRP-103 AND ASP-105.
    14. "Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity."
      Yang X., Morita M., Wang H., Suzuki T., Yang W., Luo Y., Zhao C., Yu Y., Bartlam M., Yamamoto T., Rao Z.
      Nucleic Acids Res. 36:6872-6881(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 7-128, INTERACTION WITH CNOT7, MUTAGENESIS OF TYR-65; TRP-103 AND GLU-115.

    Entry informationi

    Entry nameiBTG2_HUMAN
    AccessioniPrimary (citable) accession number: P78543
    Secondary accession number(s): A0A024R986, Q3KR25, Q5VUT0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: May 1, 1997
    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
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3