BTG2_HUMAN
ID BTG2_HUMAN Reviewed; 158 AA.
AC P78543; A0A024R986; Q3KR25; Q5VUT0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Protein BTG2;
DE AltName: Full=BTG family member 2;
DE AltName: Full=NGF-inducible anti-proliferative protein PC3;
GN Name=BTG2; Synonyms=PC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8944033; DOI=10.1038/ng1296-482;
RA Rouault J.-P., Falette N., Guehenneux F., Guillot C., Rimokh R., Wang Q.,
RA Berthet C., Moyret-Lalle C., Savatier P., Pain B., Shaw P., Berger R.,
RA Samarut J., Magaud J.-P., Ozturk M., Samarut C., Puisieux A.;
RT "Identification of BTG2, an antiproliferative p53-dependent component of
RT the DNA damage cellular response pathway.";
RL Nat. Genet. 14:482-486(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=11267995; DOI=10.1002/jcp.1062;
RA Tirone F.;
RT "The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family:
RT regulator in control of cell growth, differentiation, and DNA repair?";
RL J. Cell. Physiol. 187:155-165(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11814693; DOI=10.1016/s0378-1119(01)00825-3;
RA Duriez C., Falette N., Audoynaud C., Moyret-Lalle C., Bensaad K.,
RA Courtois S., Wang Q., Soussi T., Puisieux A.;
RT "The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional
RT regulation and evaluation as a candidate tumor suppressor gene.";
RL Gene 282:207-214(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH CNOT7.
RX PubMed=9712883; DOI=10.1074/jbc.273.35.22563;
RA Rouault J.P., Prevot D., Berthet C., Birot A.M., Billaud M., Magaud J.P.,
RA Corbo L.;
RT "Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the
RT murine homolog of a component of the yeast CCR4 transcriptional regulatory
RT complex.";
RL J. Biol. Chem. 273:22563-22569(1998).
RN [8]
RP INTERACTION WITH CNOT8.
RX PubMed=11136725; DOI=10.1074/jbc.m008201200;
RA Prevot D., Morel A.P., Voeltzel T., Rostan M.C., Rimokh R., Magaud J.P.,
RA Corbo L.;
RT "Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1,
RT the human homolog of a component of the yeast CCR4 transcriptional complex:
RT involvement in estrogen receptor alpha signaling pathway.";
RL J. Biol. Chem. 276:9640-9648(2001).
RN [9]
RP FUNCTION, AND INTERACTION WITH THE CCR4-NOT COMPLEX.
RX PubMed=12771185; DOI=10.1242/jcs.00480;
RA Morel A.-P., Sentis S., Bianchin C., Le Romancer M., Jonard L.,
RA Rostan M.-C., Rimokh R., Corbo L.;
RT "BTG2 antiproliferative protein interacts with the human CCR4 complex
RT existing in vivo in three cell-cycle-regulated forms.";
RL J. Cell Sci. 116:2929-2936(2003).
RN [10]
RP PHOSPHORYLATION AT SER-147 AND SER-149, MUTAGENESIS OF SER-147; PRO-148 AND
RP SER-149, INTERACTION WITH PIN1, AND FUNCTION.
RX PubMed=15788397; DOI=10.1074/jbc.m500318200;
RA Hong J.W., Ryu M.S., Lim I.K.;
RT "Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1
RT binding in cytoplasm and cell death.";
RL J. Biol. Chem. 280:21256-21263(2005).
RN [11]
RP FUNCTION.
RX PubMed=18337750; DOI=10.1038/emboj.2008.43;
RA Mauxion F., Faux C., Seraphin B.;
RT "The BTG2 protein is a general activator of mRNA deadenylation.";
RL EMBO J. 27:1039-1048(2008).
RN [12]
RP FUNCTION.
RX PubMed=18773938; DOI=10.1016/j.neulet.2008.08.065;
RA Miyata S., Mori Y., Tohyama M.;
RT "PRMT1 and Btg2 regulates neurite outgrowth of Neuro2a cells.";
RL Neurosci. Lett. 445:162-165(2008).
RN [13]
RP FUNCTION, INTERACTION WITH CNOT7 AND CNOT8, AND MUTAGENESIS OF HIS-53;
RP TYR-65; ASP-75; TRP-103 AND ASP-105.
RX PubMed=23236473; DOI=10.1371/journal.pone.0051331;
RA Doidge R., Mittal S., Aslam A., Winkler G.S.;
RT "The anti-proliferative activity of BTG/TOB proteins is mediated via the
RT Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not
RT complex.";
RL PLoS ONE 7:E51331-E51331(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 7-128, INTERACTION WITH CNOT7,
RP AND MUTAGENESIS OF TYR-65; TRP-103 AND GLU-115.
RX PubMed=18974182; DOI=10.1093/nar/gkn825;
RA Yang X., Morita M., Wang H., Suzuki T., Yang W., Luo Y., Zhao C., Yu Y.,
RA Bartlam M., Yamamoto T., Rao Z.;
RT "Crystal structures of human BTG2 and mouse TIS21 involved in suppression
RT of CAF1 deadenylase activity.";
RL Nucleic Acids Res. 36:6872-6881(2008).
CC -!- FUNCTION: Anti-proliferative protein; the function is mediated by
CC association with deadenylase subunits of the CCR4-NOT complex.
CC Activates mRNA deadenylation in a CNOT6 and CNOT7-dependent manner. In
CC vitro can inhibit deadenylase activity of CNOT7 and CNOT8. Involved in
CC cell cycle regulation. Could be involved in the growth arrest and
CC differentiation of the neuronal precursors (By similarity). Modulates
CC transcription regulation mediated by ESR1. Involved in mitochondrial
CC depolarization and neurite outgrowth. {ECO:0000250,
CC ECO:0000269|PubMed:12771185, ECO:0000269|PubMed:15788397,
CC ECO:0000269|PubMed:18337750, ECO:0000269|PubMed:18773938,
CC ECO:0000269|PubMed:23236473}.
CC -!- SUBUNIT: Interacts with PRKCABP (By similarity). Interacts with CNOT7
CC and CNOT8; indicative for an association with the CCR4-NOT complex.
CC Interacts with PIN1, inducing mitochondrial depolarization.
CC {ECO:0000250, ECO:0000269|PubMed:11136725, ECO:0000269|PubMed:12771185,
CC ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:18974182,
CC ECO:0000269|PubMed:23236473, ECO:0000269|PubMed:9712883}.
CC -!- INTERACTION:
CC P78543; P10275: AR; NbExp=4; IntAct=EBI-1047576, EBI-608057;
CC P78543; Q9UIV1: CNOT7; NbExp=8; IntAct=EBI-1047576, EBI-2105113;
CC P78543; Q9UFF9: CNOT8; NbExp=5; IntAct=EBI-1047576, EBI-742299;
CC P78543; Q60809: Cnot7; Xeno; NbExp=5; IntAct=EBI-1047576, EBI-2104739;
CC -!- PTM: Phosphorylated at Ser-147 by MAPK1/ERK2 and MAPK3/ERK1, and at
CC Ser-149 by MAPK14, leading to PIN1-binding and mitochondrial
CC depolarization. {ECO:0000269|PubMed:15788397}.
CC -!- SIMILARITY: Belongs to the BTG family. {ECO:0000305}.
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DR EMBL; U72649; AAB37580.1; -; mRNA.
DR EMBL; Y09943; CAA71074.1; -; mRNA.
DR EMBL; AF361937; AAL05626.1; -; Genomic_DNA.
DR EMBL; AL513326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91475.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91476.1; -; Genomic_DNA.
DR EMBL; BC105948; AAI05949.1; -; mRNA.
DR EMBL; BC105949; AAI05950.1; -; mRNA.
DR CCDS; CCDS1437.1; -.
DR RefSeq; NP_006754.1; NM_006763.2.
DR PDB; 3DJU; X-ray; 2.26 A; B=7-128.
DR PDB; 3E9V; X-ray; 1.70 A; A=8-127.
DR PDBsum; 3DJU; -.
DR PDBsum; 3E9V; -.
DR AlphaFoldDB; P78543; -.
DR SMR; P78543; -.
DR BioGRID; 113593; 21.
DR ELM; P78543; -.
DR IntAct; P78543; 5.
DR MINT; P78543; -.
DR STRING; 9606.ENSP00000290551; -.
DR GlyGen; P78543; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P78543; -.
DR PhosphoSitePlus; P78543; -.
DR BioMuta; BTG2; -.
DR DMDM; 3023409; -.
DR EPD; P78543; -.
DR MassIVE; P78543; -.
DR MaxQB; P78543; -.
DR PaxDb; P78543; -.
DR PeptideAtlas; P78543; -.
DR PRIDE; P78543; -.
DR ProteomicsDB; 57645; -.
DR Antibodypedia; 1189; 330 antibodies from 29 providers.
DR DNASU; 7832; -.
DR Ensembl; ENST00000290551.5; ENSP00000290551.4; ENSG00000159388.6.
DR Ensembl; ENST00000475157.1; ENSP00000433553.1; ENSG00000159388.6.
DR GeneID; 7832; -.
DR KEGG; hsa:7832; -.
DR MANE-Select; ENST00000290551.5; ENSP00000290551.4; NM_006763.3; NP_006754.1.
DR UCSC; uc001gzq.4; human.
DR CTD; 7832; -.
DR DisGeNET; 7832; -.
DR GeneCards; BTG2; -.
DR HGNC; HGNC:1131; BTG2.
DR HPA; ENSG00000159388; Low tissue specificity.
DR MIM; 601597; gene.
DR neXtProt; NX_P78543; -.
DR OpenTargets; ENSG00000159388; -.
DR PharmGKB; PA25451; -.
DR VEuPathDB; HostDB:ENSG00000159388; -.
DR eggNOG; KOG4006; Eukaryota.
DR GeneTree; ENSGT00950000182952; -.
DR HOGENOM; CLU_079660_4_0_1; -.
DR InParanoid; P78543; -.
DR OMA; SYGMLTC; -.
DR OrthoDB; 1439942at2759; -.
DR PhylomeDB; P78543; -.
DR TreeFam; TF105272; -.
DR PathwayCommons; P78543; -.
DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR SignaLink; P78543; -.
DR SIGNOR; P78543; -.
DR BioGRID-ORCS; 7832; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; BTG2; human.
DR EvolutionaryTrace; P78543; -.
DR GeneWiki; BTG2; -.
DR GenomeRNAi; 7832; -.
DR Pharos; P78543; Tbio.
DR PRO; PR:P78543; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P78543; protein.
DR Bgee; ENSG00000159388; Expressed in mucosa of stomach and 202 other tissues.
DR Genevisible; P78543; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
DR GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0061351; P:neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IDA:MGI.
DR GO; GO:0006479; P:protein methylation; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR Gene3D; 3.90.640.90; -; 1.
DR InterPro; IPR002087; Anti_prolifrtn.
DR InterPro; IPR033332; BTG.
DR InterPro; IPR036054; BTG-like_sf.
DR InterPro; IPR033328; BTG2.
DR PANTHER; PTHR22978; PTHR22978; 1.
DR PANTHER; PTHR22978:SF29; PTHR22978:SF29; 1.
DR Pfam; PF07742; BTG; 1.
DR PRINTS; PR00310; ANTIPRLFBTG1.
DR SMART; SM00099; btg1; 1.
DR SUPFAM; SSF160696; SSF160696; 1.
DR PROSITE; PS00960; BTG_1; 1.
DR PROSITE; PS01203; BTG_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..158
FT /note="Protein BTG2"
FT /id="PRO_0000143804"
FT MOD_RES 147
FT /note="Phosphoserine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000269|PubMed:15788397"
FT MOD_RES 149
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:15788397"
FT VARIANT 153
FT /note="V -> M (in dbSNP:rs12039961)"
FT /id="VAR_048437"
FT MUTAGEN 53
FT /note="H->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 65
FT /note="Y->A: Abolishes interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:18974182,
FT ECO:0000269|PubMed:23236473"
FT MUTAGEN 75
FT /note="D->A: Abolishes interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 103
FT /note="W->A: Abolishes interaction with CNOT7 and CNOT8;
FT impairs anti-proliferative activity."
FT /evidence="ECO:0000269|PubMed:18974182,
FT ECO:0000269|PubMed:23236473"
FT MUTAGEN 105
FT /note="D->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 115
FT /note="E->A: Impairs interaction with CNOT7. Inhibits CNOT7
FT mRNA deadenylase activity."
FT /evidence="ECO:0000269|PubMed:18974182"
FT MUTAGEN 147
FT /note="S->A: Impairs phosphorylation by MAPK1 and MAPK3,
FT and decreases PIN1-binding."
FT /evidence="ECO:0000269|PubMed:15788397"
FT MUTAGEN 148
FT /note="P->A: Impairs PIN1-binding."
FT /evidence="ECO:0000269|PubMed:15788397"
FT MUTAGEN 149
FT /note="S->A: Impairs phosphorylation by MAPK14, and
FT decreases PIN1-binding."
FT /evidence="ECO:0000269|PubMed:15788397"
FT HELIX 10..27
FT /evidence="ECO:0007829|PDB:3E9V"
FT HELIX 32..50
FT /evidence="ECO:0007829|PDB:3E9V"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:3E9V"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:3E9V"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:3E9V"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:3E9V"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:3E9V"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:3E9V"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:3E9V"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:3E9V"
SQ SEQUENCE 158 AA; 17416 MW; FFAA1844CC360209 CRC64;
MSHGKGTDML PEIAAAVGFL SSLLRTRGCV SEQRLKVFSG ALQEALTEHY KHHWFPEKPS
KGSGYRCIRI NHKMDPIISR VASQIGLSQP QLHQLLPSEL TLWVDPYEVS YRIGEDGSIC
VLYEEAPLAA SCGLLTCKNQ VLLGRSSPSK NYVMAVSS
