TBRG1_HUMAN
ID TBRG1_HUMAN Reviewed; 411 AA.
AC Q3YBR2; Q53GJ5; Q66ZJ6; Q69YS7; Q8TCS4; Q8TEI4; Q96SV0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Transforming growth factor beta regulator 1;
DE AltName: Full=Nuclear interactor of ARF and Mdm2;
GN Name=TBRG1; Synonyms=NIAM;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INTERACTION WITH CDKN2A AND MDM2, AND UBIQUITINATION.
RC TISSUE=Pancreas;
RX PubMed=17110379; DOI=10.1074/jbc.m609612200;
RA Tompkins V.S., Hagen J., Frazier A.A., Lushnikova T., Fitzgerald M.P.,
RA di Tommaso A.D., Ladeveze V., Domann F.E., Eischen C.M., Quelle D.E.;
RT "A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains
RT chromosomal stability.";
RL J. Biol. Chem. 282:1322-1333(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Zhou G., Li M., Li H., Shen C., Zhong G., Lin L., Yang S.;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 220-411.
RC TISSUE=Amygdala, and Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP INTERACTION WITH CDKN2A.
RX PubMed=16582619;
RA Tompkins V., Hagen J., Zediak V.P., Quelle D.E.;
RT "Identification of novel ARF binding proteins by two-hybrid screening.";
RL Cell Cycle 5:641-646(2006).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-10, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP 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 [10]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 179-324.
RX PubMed=20506279; DOI=10.1002/pro.404;
RA Garcia-Alai M.M., Allen M.D., Joerger A.C., Bycroft M.;
RT "The structure of the FYR domain of transforming growth factor beta
RT regulator 1.";
RL Protein Sci. 19:1432-1438(2010).
CC -!- FUNCTION: Acts as a growth inhibitor. Can activate p53/TP53, causes G1
CC arrest and collaborates with CDKN2A to restrict proliferation, but does
CC not require either protein to inhibit DNA synthesis. Redistributes
CC CDKN2A into the nucleoplasm. Involved in maintaining chromosomal
CC stability. {ECO:0000269|PubMed:17110379}.
CC -!- SUBUNIT: Interacts with CDKN2A and MDM2. {ECO:0000269|PubMed:16582619,
CC ECO:0000269|PubMed:17110379}.
CC -!- INTERACTION:
CC Q3YBR2; O14645: DNALI1; NbExp=3; IntAct=EBI-2800552, EBI-395638;
CC Q3YBR2; O14901: KLF11; NbExp=3; IntAct=EBI-2800552, EBI-948266;
CC Q3YBR2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2800552, EBI-25882629;
CC Q3YBR2; Q8NB12: SMYD1; NbExp=3; IntAct=EBI-2800552, EBI-8463848;
CC Q3YBR2; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-2800552, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17110379}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3YBR2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3YBR2-2; Sequence=VSP_022645;
CC Name=3;
CC IsoId=Q3YBR2-3; Sequence=VSP_022644;
CC -!- TISSUE SPECIFICITY: Widely expressed at low levels in most tissues,
CC with highest levels in pancreas, lung and liver. Expression is
CC decreased in primary tumors including lung, liver, breast, pancreas and
CC kidney carcinomas, chronic lymphocytic leukemia and diffuse large B-
CC cell lymphoma. {ECO:0000269|PubMed:17110379}.
CC -!- PTM: Ubiquitinated; mediated by MDM2 and leading to its subsequent
CC proteasomal degradation. {ECO:0000269|PubMed:17110379}.
CC -!- SIMILARITY: Belongs to the TBRG1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84966.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; DQ144542; AAZ76016.1; -; mRNA.
DR EMBL; AK027527; BAB55177.1; -; mRNA.
DR EMBL; AK074140; BAB84966.1; ALT_FRAME; mRNA.
DR EMBL; AY696294; AAU10523.1; -; mRNA.
DR EMBL; AK222936; BAD96656.1; -; mRNA.
DR EMBL; BC109269; AAI09270.1; -; mRNA.
DR EMBL; AL713631; CAD28450.1; -; mRNA.
DR EMBL; AL831881; CAH10595.1; -; mRNA.
DR CCDS; CCDS8448.2; -. [Q3YBR2-1]
DR RefSeq; NP_116200.2; NM_032811.2. [Q3YBR2-1]
DR RefSeq; XP_016873931.1; XM_017018442.1. [Q3YBR2-2]
DR PDB; 2WZO; X-ray; 1.60 A; A=179-324.
DR PDBsum; 2WZO; -.
DR AlphaFoldDB; Q3YBR2; -.
DR SMR; Q3YBR2; -.
DR BioGRID; 124337; 22.
DR IntAct; Q3YBR2; 21.
DR STRING; 9606.ENSP00000409016; -.
DR iPTMnet; Q3YBR2; -.
DR PhosphoSitePlus; Q3YBR2; -.
DR BioMuta; TBRG1; -.
DR DMDM; 121943045; -.
DR EPD; Q3YBR2; -.
DR jPOST; Q3YBR2; -.
DR MassIVE; Q3YBR2; -.
DR MaxQB; Q3YBR2; -.
DR PaxDb; Q3YBR2; -.
DR PeptideAtlas; Q3YBR2; -.
DR PRIDE; Q3YBR2; -.
DR ProteomicsDB; 61892; -. [Q3YBR2-1]
DR ProteomicsDB; 61893; -. [Q3YBR2-2]
DR ProteomicsDB; 61894; -. [Q3YBR2-3]
DR Antibodypedia; 45986; 147 antibodies from 25 providers.
DR DNASU; 84897; -.
DR Ensembl; ENST00000441174.8; ENSP00000409016.3; ENSG00000154144.13. [Q3YBR2-1]
DR GeneID; 84897; -.
DR KEGG; hsa:84897; -.
DR MANE-Select; ENST00000441174.8; ENSP00000409016.3; NM_032811.3; NP_116200.2.
DR UCSC; uc001qak.5; human. [Q3YBR2-1]
DR CTD; 84897; -.
DR DisGeNET; 84897; -.
DR GeneCards; TBRG1; -.
DR HGNC; HGNC:29551; TBRG1.
DR HPA; ENSG00000154144; Low tissue specificity.
DR MIM; 610614; gene.
DR neXtProt; NX_Q3YBR2; -.
DR OpenTargets; ENSG00000154144; -.
DR PharmGKB; PA134926528; -.
DR VEuPathDB; HostDB:ENSG00000154144; -.
DR eggNOG; KOG4443; Eukaryota.
DR GeneTree; ENSGT00390000013374; -.
DR HOGENOM; CLU_037126_0_0_1; -.
DR InParanoid; Q3YBR2; -.
DR OMA; FFGISHP; -.
DR OrthoDB; 1397649at2759; -.
DR PhylomeDB; Q3YBR2; -.
DR TreeFam; TF324736; -.
DR PathwayCommons; Q3YBR2; -.
DR SignaLink; Q3YBR2; -.
DR BioGRID-ORCS; 84897; 9 hits in 1080 CRISPR screens.
DR ChiTaRS; TBRG1; human.
DR EvolutionaryTrace; Q3YBR2; -.
DR GeneWiki; TBRG1; -.
DR GenomeRNAi; 84897; -.
DR Pharos; Q3YBR2; Tbio.
DR PRO; PR:Q3YBR2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q3YBR2; protein.
DR Bgee; ENSG00000154144; Expressed in granulocyte and 178 other tissues.
DR ExpressionAtlas; Q3YBR2; baseline and differential.
DR Genevisible; Q3YBR2; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IMP:HGNC-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:HGNC-UCL.
DR GO; GO:1990173; P:protein localization to nucleoplasm; IDA:HGNC-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:HGNC-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:HGNC-UCL.
DR InterPro; IPR003889; FYrich_C.
DR InterPro; IPR003888; FYrich_N.
DR InterPro; IPR040092; TBRG1.
DR PANTHER; PTHR22715; PTHR22715; 1.
DR Pfam; PF05965; FYRC; 1.
DR Pfam; PF05964; FYRN; 1.
DR SMART; SM00542; FYRC; 1.
DR SMART; SM00541; FYRN; 1.
DR PROSITE; PS51543; FYRC; 1.
DR PROSITE; PS51542; FYRN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Nucleus;
KW Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CHAIN 2..411
FT /note="Transforming growth factor beta regulator 1"
FT /id="PRO_0000274218"
FT DOMAIN 182..241
FT /note="FYR N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875"
FT DOMAIN 242..321
FT /note="FYR C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..146
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..224
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022644"
FT VAR_SEQ 1..197
FT /note="MSLLDGLASSPRAPLQSSKARMKKLPKKSQNEKYRLKYLRLRKAAKATVFEN
FT AAICDEIARLEEKFLKAKEERRYLLKKLLQLQALTEGEVQAAAPSHSSSLPLTYGVASS
FT VGTIQGAGPISGPSTGAEEPFGKKTKKEKKEKGKENNKLEVLKKTCKKKKMAGGARKLV
FT QPIALDPSGRPVFPIGLGGLTVYSLGE -> MVWPALWELYRELGLFQGPALGLRNHLG
FT RKLRRRKKKKAKRTTNWK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_022645"
FT CONFLICT 406
FT /note="P -> S (in Ref. 4; BAD96656)"
FT /evidence="ECO:0000305"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:2WZO"
FT STRAND 190..197
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:2WZO"
FT STRAND 214..223
FT /evidence="ECO:0007829|PDB:2WZO"
FT STRAND 230..240
FT /evidence="ECO:0007829|PDB:2WZO"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:2WZO"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 264..279
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 290..294
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 299..305
FT /evidence="ECO:0007829|PDB:2WZO"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:2WZO"
SQ SEQUENCE 411 AA; 44946 MW; C6FDE7D7961E78C4 CRC64;
MSLLDGLASS PRAPLQSSKA RMKKLPKKSQ NEKYRLKYLR LRKAAKATVF ENAAICDEIA
RLEEKFLKAK EERRYLLKKL LQLQALTEGE VQAAAPSHSS SLPLTYGVAS SVGTIQGAGP
ISGPSTGAEE PFGKKTKKEK KEKGKENNKL EVLKKTCKKK KMAGGARKLV QPIALDPSGR
PVFPIGLGGL TVYSLGEIIT DRPGFHDESA IYPVGYCSTR IYASMKCPDQ KCLYTCQIKD
GGVQPQFEIV PEDDPQNAIV SSSADACHAE LLRTISTTMG KLMPNLLPAG ADFFGFSHPA
IHNLIQSCPG ARKCINYQWV KFDVCKPGDG QLPEGLPEND AAMSFEAFQR QIFDEDQNDP
LLPGSLDLPE LQPAAFVSSY QPMYLTHEPL VDTHLQHLKS PSQGSPIQSS D
