TOB1_HUMAN
ID TOB1_HUMAN Reviewed; 345 AA.
AC P50616; B2R9T0; D3DTY3; Q4KMQ0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Protein Tob1;
DE AltName: Full=Transducer of erbB-2 1;
GN Name=TOB1; Synonyms=TOB, TROB1;
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], FUNCTION, AND INTERACTION WITH ERBB2.
RX PubMed=8632892;
RA Matsuda S., Kawamura-Tsuzuku J., Ohsugi M., Yoshida M., Emi M.,
RA Nakamura Y., Onda M., Yoshida Y., Nishiyama A., Yamamoto T.;
RT "Tob, a novel protein that interacts with p185erbB2, is associated with
RT anti-proliferative activity.";
RL Oncogene 12:705-713(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Prostate, and Uterus;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP FUNCTION, AND INTERACTION WITH CNOT7; CPEB3 AND CPEB4.
RX PubMed=21336257; DOI=10.1038/emboj.2011.37;
RA Hosoda N., Funakoshi Y., Hirasawa M., Yamagishi R., Asano Y., Miyagawa R.,
RA Ogami K., Tsujimoto M., Hoshino S.;
RT "Anti-proliferative protein Tob negatively regulates CPEB3 target by
RT recruiting Caf1 deadenylase.";
RL EMBO J. 30:1311-1323(2011).
RN [11]
RP FUNCTION, INTERACTION WITH CNOT7 AND CNOT8, AND MUTAGENESIS OF TYR-45;
RP PHE-55; ASP-65; TRP-93 AND ASP-95.
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-115 IN COMPLEX WITH CNOT7.
RX PubMed=19276069; DOI=10.1074/jbc.m809250200;
RA Horiuchi M., Takeuchi K., Noda N., Muroya N., Suzuki T., Nakamura T.,
RA Kawamura-Tsuzuku J., Takahasi K., Yamamoto T., Inagaki F.;
RT "Structural basis for the antiproliferative activity of the Tob-hCaf1
RT complex.";
RL J. Biol. Chem. 284:13244-13255(2009).
CC -!- FUNCTION: Anti-proliferative protein; the function is mediated by
CC association with deadenylase subunits of the CCR4-NOT complex
CC (PubMed:8632892, PubMed:23236473). Mediates CPEB3-accelerated mRNA
CC deadenylation by binding to CPEB3 and recruiting CNOT7 which leads to
CC target mRNA deadenylation and decay (PubMed:21336257).
CC {ECO:0000269|PubMed:21336257, ECO:0000269|PubMed:23236473,
CC ECO:0000269|PubMed:8632892}.
CC -!- SUBUNIT: Interacts with ERBB2 (PubMed:8632892). Interacts with CNOT7
CC (PubMed:19276069, PubMed:21336257, PubMed:23236473). Interacts with
CC CPEB3 (via C-terminal RNA-binding region); recruits CNOT7 to CPEB3 to
CC form a ternary complex required for mRNA deadenylation and decay
CC (PubMed:21336257). Interacts with CNOT8 (PubMed:23236473). Interacts
CC with CPEB4 (PubMed:21336257). {ECO:0000269|PubMed:19276069,
CC ECO:0000269|PubMed:21336257, ECO:0000269|PubMed:23236473,
CC ECO:0000269|PubMed:8632892}.
CC -!- INTERACTION:
CC P50616; A5YKK6: CNOT1; NbExp=4; IntAct=EBI-723281, EBI-1222758;
CC P50616; O75175: CNOT3; NbExp=3; IntAct=EBI-723281, EBI-743073;
CC P50616; Q96LI5: CNOT6L; NbExp=4; IntAct=EBI-723281, EBI-1046635;
CC P50616; Q9UIV1: CNOT7; NbExp=9; IntAct=EBI-723281, EBI-2105113;
CC P50616; Q8NE35: CPEB3; NbExp=7; IntAct=EBI-723281, EBI-8596191;
CC P50616; Q17RY0: CPEB4; NbExp=2; IntAct=EBI-723281, EBI-2848203;
CC P50616; P22607: FGFR3; NbExp=3; IntAct=EBI-723281, EBI-348399;
CC P50616; P06396: GSN; NbExp=3; IntAct=EBI-723281, EBI-351506;
CC P50616; P11940: PABPC1; NbExp=5; IntAct=EBI-723281, EBI-81531;
CC P50616; Q13148: TARDBP; NbExp=4; IntAct=EBI-723281, EBI-372899;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Only a small fraction localizes to the cytoplasm except in late S-
CC phase where more than half of proteins become cytoplasmic.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylated on Ser and Thr residues.
CC -!- SIMILARITY: Belongs to the BTG family. {ECO:0000305}.
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DR EMBL; D38305; BAA07423.1; -; mRNA.
DR EMBL; CR536487; CAG38726.1; -; mRNA.
DR EMBL; CR541686; CAG46487.1; -; mRNA.
DR EMBL; BT019380; AAV38187.1; -; mRNA.
DR EMBL; BT019381; AAV38188.1; -; mRNA.
DR EMBL; AK313904; BAG36627.1; -; mRNA.
DR EMBL; CH471109; EAW94577.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94578.1; -; Genomic_DNA.
DR EMBL; BC031406; AAH31406.1; -; mRNA.
DR EMBL; BC070493; AAH70493.1; -; mRNA.
DR EMBL; BC098415; AAH98415.1; -; mRNA.
DR CCDS; CCDS11576.1; -.
DR RefSeq; NP_001230806.1; NM_001243877.1.
DR RefSeq; NP_001230814.1; NM_001243885.1.
DR RefSeq; NP_005740.1; NM_005749.3.
DR PDB; 2D5R; X-ray; 2.50 A; B=1-115.
DR PDB; 2Z15; X-ray; 2.30 A; A/B/C/D=1-117.
DR PDB; 5CI8; X-ray; 2.33 A; A=1-345.
DR PDB; 5CI9; X-ray; 2.30 A; A=1-345.
DR PDBsum; 2D5R; -.
DR PDBsum; 2Z15; -.
DR PDBsum; 5CI8; -.
DR PDBsum; 5CI9; -.
DR AlphaFoldDB; P50616; -.
DR SMR; P50616; -.
DR BioGRID; 115443; 41.
DR IntAct; P50616; 41.
DR MINT; P50616; -.
DR STRING; 9606.ENSP00000427695; -.
DR GlyGen; P50616; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50616; -.
DR PhosphoSitePlus; P50616; -.
DR BioMuta; TOB1; -.
DR DMDM; 1729989; -.
DR EPD; P50616; -.
DR jPOST; P50616; -.
DR MassIVE; P50616; -.
DR MaxQB; P50616; -.
DR PaxDb; P50616; -.
DR PeptideAtlas; P50616; -.
DR PRIDE; P50616; -.
DR ProteomicsDB; 56259; -.
DR Antibodypedia; 4398; 295 antibodies from 32 providers.
DR DNASU; 10140; -.
DR Ensembl; ENST00000268957.3; ENSP00000268957.3; ENSG00000141232.5.
DR Ensembl; ENST00000499247.3; ENSP00000427695.1; ENSG00000141232.5.
DR GeneID; 10140; -.
DR KEGG; hsa:10140; -.
DR MANE-Select; ENST00000499247.3; ENSP00000427695.1; NM_005749.4; NP_005740.1.
DR UCSC; uc002isw.4; human.
DR CTD; 10140; -.
DR DisGeNET; 10140; -.
DR GeneCards; TOB1; -.
DR HGNC; HGNC:11979; TOB1.
DR HPA; ENSG00000141232; Low tissue specificity.
DR MIM; 605523; gene.
DR neXtProt; NX_P50616; -.
DR OpenTargets; ENSG00000141232; -.
DR PharmGKB; PA36663; -.
DR VEuPathDB; HostDB:ENSG00000141232; -.
DR eggNOG; KOG4006; Eukaryota.
DR GeneTree; ENSGT00940000154208; -.
DR HOGENOM; CLU_034687_0_0_1; -.
DR InParanoid; P50616; -.
DR OMA; MKNSGRG; -.
DR OrthoDB; 1439942at2759; -.
DR PhylomeDB; P50616; -.
DR TreeFam; TF105274; -.
DR PathwayCommons; P50616; -.
DR SignaLink; P50616; -.
DR SIGNOR; P50616; -.
DR BioGRID-ORCS; 10140; 13 hits in 1077 CRISPR screens.
DR ChiTaRS; TOB1; human.
DR EvolutionaryTrace; P50616; -.
DR GeneWiki; TOB1; -.
DR GenomeRNAi; 10140; -.
DR Pharos; P50616; Tbio.
DR PRO; PR:P50616; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P50616; protein.
DR Bgee; ENSG00000141232; Expressed in mucosa of paranasal sinus and 204 other tissues.
DR Genevisible; P50616; HS.
DR GO; GO:0030014; C:CCR4-NOT complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0060212; P:negative regulation of nuclear-transcribed mRNA poly(A) tail shortening; IDA:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; IEA:Ensembl.
DR DisProt; DP00794; -.
DR Gene3D; 3.90.640.90; -; 1.
DR IDEAL; IID00453; -.
DR InterPro; IPR002087; Anti_prolifrtn.
DR InterPro; IPR036054; BTG-like_sf.
DR InterPro; IPR015677; Tob1.
DR InterPro; IPR015676; Tob1/2.
DR PANTHER; PTHR17537; PTHR17537; 1.
DR PANTHER; PTHR17537:SF6; PTHR17537:SF6; 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; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..345
FT /note="Protein Tob1"
FT /id="PRO_0000143812"
FT REGION 82..92
FT /note="Important for nuclear localization"
FT /evidence="ECO:0000250"
FT REGION 144..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..218
FT /note="Required for interaction with CPEB3"
FT /evidence="ECO:0000269|PubMed:21336257"
FT REGION 231..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 22..39
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 226..234
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 244..259
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 204
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VARIANT 319
FT /note="K -> R (in dbSNP:rs3316)"
FT /id="VAR_037840"
FT MUTAGEN 45
FT /note="Y->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 55
FT /note="F->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 65
FT /note="D->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 93
FT /note="W->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT MUTAGEN 95
FT /note="D->A: Impairs interaction with CNOT7 and CNOT8."
FT /evidence="ECO:0000269|PubMed:23236473"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:2Z15"
FT TURN 14..19
FT /evidence="ECO:0007829|PDB:2Z15"
FT HELIX 22..40
FT /evidence="ECO:0007829|PDB:2Z15"
FT TURN 49..52
FT /evidence="ECO:0007829|PDB:2Z15"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:2Z15"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:2Z15"
FT HELIX 66..73
FT /evidence="ECO:0007829|PDB:2Z15"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:2Z15"
FT HELIX 79..85
FT /evidence="ECO:0007829|PDB:2Z15"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:2Z15"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:2Z15"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:2Z15"
SQ SEQUENCE 345 AA; 38155 MW; 3C8AC51B49E1E69F CRC64;
MQLEIQVALN FIISYLYNKL PRRRVNIFGE ELERLLKKKY EGHWYPEKPY KGSGFRCIHI
GEKVDPVIEQ ASKESGLDID DVRGNLPQDL SVWIDPFEVS YQIGEKGPVK VLYVDDNNEN
GCELDKEIKN SFNPEAQVFM PISDPASSVS SSPSPPFGHS AAVSPTFMPR STQPLTFTTA
TFAATKFGST KMKNSGRSNK VARTSPINLG LNVNDLLKQK AISSSMHSLY GLGLGSQQQP
QQQQQPAQPP PPPPPPQQQQ QQKTSALSPN AKEFIFPNMQ GQGSSTNGMF PGDSPLNLSP
LQYSNAFDVF AAYGGLNEKS FVDGLNFSLN NMQYSNQQFQ PVMAN
