TNR6C_HUMAN
ID TNR6C_HUMAN Reviewed; 1690 AA.
AC Q9HCJ0; G3XAB8; Q86UE5; Q8N3D8; Q96MU9;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Trinucleotide repeat-containing gene 6C protein;
GN Name=TNRC6C; Synonyms=KIAA1582;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORM 1).
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
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 (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 627-1690 (ISOFORM 1).
RC TISSUE=Melanoma;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 728-1690 (ISOFORM 2).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1146-1690 (ISOFORM 2).
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 [8]
RP INTERACTION WITH PABPC1 AND EIF4G1.
RX PubMed=19716330; DOI=10.1016/j.molcel.2009.08.004;
RA Fabian M.R., Mathonnet G., Sundermeier T., Mathys H., Zipprich J.T.,
RA Svitkin Y.V., Rivas F., Jinek M., Wohlschlegel J., Doudna J.A., Chen C.Y.,
RA Shyu A.B., Yates J.R. III, Hannon G.J., Filipowicz W., Duchaine T.F.,
RA Sonenberg N.;
RT "Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent
RT deadenylation.";
RL Mol. Cell 35:868-880(2009).
RN [9]
RP FUNCTION, INTERACTION WITH ARGONAUTE PROTEINS, AND MUTAGENESIS OF HIS-1537;
RP PHE-1543 AND TYR-1556.
RX PubMed=19304925; DOI=10.1261/rna.1448009;
RA Zipprich J.T., Bhattacharyya S., Mathys H., Filipowicz W.;
RT "Importance of the C-terminal domain of the human GW182 protein TNRC6C for
RT translational repression.";
RL RNA 15:781-793(2009).
RN [10]
RP INTERACTION WITH AGO1; AGO2; AGO3 AND AGO4.
RX PubMed=19383768; DOI=10.1261/rna.1606309;
RA Lazzaretti D., Tournier I., Izaurralde E.;
RT "The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound
RT transcripts independently of Argonaute proteins.";
RL RNA 15:1059-1066(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714, 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 [12]
RP FUNCTION, AND INTERACTION WITH CNOT1 AND PAN3.
RX PubMed=21981923; DOI=10.1016/j.molcel.2011.09.007;
RA Braun J.E., Huntzinger E., Fauser M., Izaurralde E.;
RT "GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA
RT targets.";
RL Mol. Cell 44:120-133(2011).
RN [13]
RP FUNCTION, INTERACTION WITH CNOT1, AND MUTAGENESIS OF 1294-GLN--TRP-1300;
RP 1388-GLU-PHE-1389; 1395-TRP-LYS-1396; 1647-LEU--GLY-1449 AND
RP 1658-LEU--GLY-1660.
RX PubMed=21984185; DOI=10.1038/nsmb.2149;
RA Fabian M.R., Cieplak M.K., Frank F., Morita M., Green J., Srikumar T.,
RA Nagar B., Yamamoto T., Raught B., Duchaine T.F., Sonenberg N.;
RT "miRNA-mediated deadenylation is orchestrated by GW182 through two
RT conserved motifs that interact with CCR4-NOT.";
RL Nat. Struct. Mol. Biol. 18:1211-1217(2011).
RN [14]
RP FUNCTION, INTERACTION WITH PABPC1 AND THE CCR4-NOT COMPLEX, AND MUTAGENESIS
RP OF TRP-1445; TRP-1487; TRP-1494; TRP-1504; TRP-1515; TRP-1605 AND TRP-1648.
RX PubMed=21984184; DOI=10.1038/nsmb.2166;
RA Chekulaeva M., Mathys H., Zipprich J.T., Attig J., Colic M., Parker R.,
RA Filipowicz W.;
RT "miRNA repression involves GW182-mediated recruitment of CCR4-NOT through
RT conserved W-containing motifs.";
RL Nat. Struct. Mol. Biol. 18:1218-1226(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714 AND SER-1011, AND
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-777, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-313, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [18]
RP STRUCTURE BY NMR OF 927-998.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the UBA domain in the human trinucleotide repeat
RT containing 6C protein (HTNRC6C).";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Plays a role in RNA-mediated gene silencing by micro-RNAs
CC (miRNAs). Required for miRNA-dependent translational repression of
CC complementary mRNAs by argonaute family proteins. As scaffoldng protein
CC associates with argonaute proteins bound to partially complementary
CC mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase
CC complexes. {ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923,
CC ECO:0000269|PubMed:21984184, ECO:0000269|PubMed:21984185}.
CC -!- SUBUNIT: Interacts with one or more of the argonaute family proteins
CC AGO1, AGO2, AGO3 and AGO4. Interacts with PABPC1 and EIF4G1. Interacts
CC with CNOT1; the interaction is direct and mediates the association with
CC the CCR4-NOT complex. Interacts with PAN3; the interaction mediates the
CC association with the PAN complex. {ECO:0000269|PubMed:19304925,
CC ECO:0000269|PubMed:19383768, ECO:0000269|PubMed:19716330,
CC ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:21984184,
CC ECO:0000269|PubMed:21984185}.
CC -!- INTERACTION:
CC Q9HCJ0; Q9UKV8: AGO2; NbExp=4; IntAct=EBI-6507625, EBI-528269;
CC Q9HCJ0; A5YKK6: CNOT1; NbExp=16; IntAct=EBI-6507625, EBI-1222758;
CC Q9HCJ0; Q9H9A5: CNOT10; NbExp=10; IntAct=EBI-6507625, EBI-1054261;
CC Q9HCJ0; Q9NZN8: CNOT2; NbExp=4; IntAct=EBI-6507625, EBI-743033;
CC Q9HCJ0; O75175: CNOT3; NbExp=10; IntAct=EBI-6507625, EBI-743073;
CC Q9HCJ0; Q9ULM6: CNOT6; NbExp=2; IntAct=EBI-6507625, EBI-2104530;
CC Q9HCJ0; Q96LI5: CNOT6L; NbExp=6; IntAct=EBI-6507625, EBI-1046635;
CC Q9HCJ0; Q9UIV1: CNOT7; NbExp=9; IntAct=EBI-6507625, EBI-2105113;
CC Q9HCJ0; P11940: PABPC1; NbExp=22; IntAct=EBI-6507625, EBI-81531;
CC Q9HCJ0; Q504Q3: PAN2; NbExp=7; IntAct=EBI-6507625, EBI-1058976;
CC Q9HCJ0; Q58A45: PAN3; NbExp=4; IntAct=EBI-6507625, EBI-2513054;
CC Q9HCJ0; Q8CJG0: Ago2; Xeno; NbExp=3; IntAct=EBI-6507625, EBI-528299;
CC Q9HCJ0; P21187: pAbp; Xeno; NbExp=5; IntAct=EBI-6507625, EBI-103658;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HCJ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HCJ0-2; Sequence=VSP_054230, VSP_023322;
CC -!- DOMAIN: The silencing domain, also known as C-terminal effector domain
CC (CED), can act in autonomous repression, including both translational
CC inhibition and mRNA degradation.
CC -!- SIMILARITY: Belongs to the GW182 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13408.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB71179.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB046802; BAB13408.2; ALT_INIT; mRNA.
DR EMBL; AC021593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC015804; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89480.1; -; Genomic_DNA.
DR EMBL; AL834429; CAD39090.1; -; mRNA.
DR EMBL; BC045631; AAH45631.1; -; mRNA.
DR EMBL; AK056421; BAB71179.1; ALT_INIT; mRNA.
DR CCDS; CCDS45798.1; -. [Q9HCJ0-1]
DR CCDS; CCDS45799.1; -. [Q9HCJ0-2]
DR RefSeq; NP_001136112.1; NM_001142640.1. [Q9HCJ0-2]
DR RefSeq; NP_061869.2; NM_018996.3. [Q9HCJ0-1]
DR PDB; 2DKL; NMR; -; A=927-998.
DR PDB; 2X04; X-ray; 1.49 A; C/D=1382-1399.
DR PDB; 3KTP; X-ray; 1.50 A; B=1380-1401.
DR PDBsum; 2DKL; -.
DR PDBsum; 2X04; -.
DR PDBsum; 3KTP; -.
DR AlphaFoldDB; Q9HCJ0; -.
DR SMR; Q9HCJ0; -.
DR BioGRID; 121716; 126.
DR DIP; DIP-48569N; -.
DR ELM; Q9HCJ0; -.
DR IntAct; Q9HCJ0; 45.
DR MINT; Q9HCJ0; -.
DR STRING; 9606.ENSP00000336783; -.
DR GlyGen; Q9HCJ0; 11 sites, 2 O-linked glycans (11 sites).
DR iPTMnet; Q9HCJ0; -.
DR PhosphoSitePlus; Q9HCJ0; -.
DR BioMuta; TNRC6C; -.
DR DMDM; 126253813; -.
DR EPD; Q9HCJ0; -.
DR jPOST; Q9HCJ0; -.
DR MassIVE; Q9HCJ0; -.
DR MaxQB; Q9HCJ0; -.
DR PaxDb; Q9HCJ0; -.
DR PeptideAtlas; Q9HCJ0; -.
DR PRIDE; Q9HCJ0; -.
DR ProteomicsDB; 33705; -.
DR ProteomicsDB; 81734; -. [Q9HCJ0-1]
DR ProteomicsDB; 81735; -. [Q9HCJ0-2]
DR Antibodypedia; 32505; 66 antibodies from 14 providers.
DR DNASU; 57690; -.
DR Ensembl; ENST00000301624.8; ENSP00000301624.4; ENSG00000078687.17. [Q9HCJ0-1]
DR Ensembl; ENST00000335749.4; ENSP00000336783.4; ENSG00000078687.17. [Q9HCJ0-2]
DR Ensembl; ENST00000588061.5; ENSP00000468647.1; ENSG00000078687.17. [Q9HCJ0-1]
DR Ensembl; ENST00000588847.5; ENSP00000467154.1; ENSG00000078687.17. [Q9HCJ0-2]
DR GeneID; 57690; -.
DR KEGG; hsa:57690; -.
DR UCSC; uc002juc.3; human. [Q9HCJ0-1]
DR CTD; 57690; -.
DR DisGeNET; 57690; -.
DR GeneCards; TNRC6C; -.
DR HGNC; HGNC:29318; TNRC6C.
DR HPA; ENSG00000078687; Tissue enhanced (retina).
DR MIM; 610741; gene.
DR neXtProt; NX_Q9HCJ0; -.
DR OpenTargets; ENSG00000078687; -.
DR PharmGKB; PA134880671; -.
DR VEuPathDB; HostDB:ENSG00000078687; -.
DR eggNOG; ENOG502QWFQ; Eukaryota.
DR GeneTree; ENSGT00940000157598; -.
DR HOGENOM; CLU_001298_3_0_1; -.
DR InParanoid; Q9HCJ0; -.
DR OrthoDB; 50428at2759; -.
DR PhylomeDB; Q9HCJ0; -.
DR TreeFam; TF329702; -.
DR PathwayCommons; Q9HCJ0; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-426496; Post-transcriptional silencing by small RNAs.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-HSA-8943723; Regulation of PTEN mRNA translation.
DR Reactome; R-HSA-8948700; Competing endogenous RNAs (ceRNAs) regulate PTEN translation.
DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR SignaLink; Q9HCJ0; -.
DR BioGRID-ORCS; 57690; 18 hits in 1082 CRISPR screens.
DR ChiTaRS; TNRC6C; human.
DR EvolutionaryTrace; Q9HCJ0; -.
DR GenomeRNAi; 57690; -.
DR Pharos; Q9HCJ0; Tbio.
DR PRO; PR:Q9HCJ0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9HCJ0; protein.
DR Bgee; ENSG00000078687; Expressed in sural nerve and 174 other tissues.
DR ExpressionAtlas; Q9HCJ0; baseline and differential.
DR Genevisible; Q9HCJ0; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; IGI:BHF-UCL.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; TAS: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 CDD; cd12713; RRM_TNRC6C; 1.
DR CDD; cd14283; UBA_TNR6C; 1.
DR DisProt; DP01324; -.
DR Gene3D; 3.30.70.330; -; 1.
DR IDEAL; IID00587; -.
DR InterPro; IPR019486; Argonaute_hook_dom.
DR InterPro; IPR026805; GW182_M_dom.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR041917; TNR6C_UBA.
DR InterPro; IPR032226; TNRC6_PABC-bd.
DR InterPro; IPR033499; TNRC6C.
DR InterPro; IPR034927; TNRC6C_RRM.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR13020:SF9; PTHR13020:SF9; 2.
DR Pfam; PF10427; Ago_hook; 1.
DR Pfam; PF12938; M_domain; 1.
DR Pfam; PF16608; TNRC6-PABC_bdg; 2.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Methylation;
KW Phosphoprotein; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing; Translation regulation.
FT CHAIN 1..1690
FT /note="Trinucleotide repeat-containing gene 6C protein"
FT /id="PRO_0000278526"
FT DOMAIN 933..978
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 1565..1632
FT /note="RRM"
FT REGION 1..926
FT /note="Sufficient for interaction with argonaute family
FT proteins"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 552..721
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..825
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 908..932
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1084..1105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1212..1380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1260..1690
FT /note="Silencing domain; interaction with CNOT1 and PAN3"
FT /evidence="ECO:0000269|PubMed:21981923"
FT REGION 1371..1690
FT /note="Sufficient for translational repression when
FT tethered to a target mRNA"
FT REGION 1371..1417
FT /note="Required for interaction with PABPC1"
FT REGION 1381..1399
FT /note="PABPC1-interacting motif-2 (PAM2)"
FT REGION 1398..1421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1441..1486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1596..1690
FT /note="Interaction with the CCR4-NOT complex"
FT REGION 1602..1623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1156..1214
FT /evidence="ECO:0000255"
FT COMPBIAS 1..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..429
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 619..685
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..789
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1212..1226
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1236..1264
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1271..1318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1345..1359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1441..1465
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1602..1619
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 313
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHC0"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 777
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1011
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 796..798
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054230"
FT VAR_SEQ 1435
FT /note="G -> GGSSPPSSQNATLPSSSAWPLSASGYSSSFSSIASAPSVA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_023322"
FT VARIANT 820
FT /note="P -> R (in dbSNP:rs34293811)"
FT /id="VAR_052237"
FT MUTAGEN 1294..1300
FT /note="QSRLPQW->AAAAPAA: Abolishes association with CCR4-
FT NOT complex."
FT MUTAGEN 1388..1389
FT /note="EF->AA: Abolishes interaction with PABPC1, impairs
FT interaction with PAN2, no effect on interaction with CCR4-
FT NOT complex, reduces RNA deadenylation rate; when
FT associated with 1395-A-A-1396."
FT MUTAGEN 1395..1396
FT /note="WK->AA: Abolishes interaction with PABPC1, impairs
FT interaction with PAN2, no effect on interaction with CCR4-
FT NOT complex, reduces RNA deadenylation rate; when
FT associated with 1388-A-A-1389."
FT MUTAGEN 1445
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1487, A-1494, A-
FT 1504, A-1515, A-1605 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1487
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1494, A-
FT 1504, A-1515, A-1605 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1494
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1487, A-
FT 1504, A-1515, A-1605 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1504
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1487, A-
FT 1494, A-1515, A-1605 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1515
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1487, A-
FT 1494, A-1504, A-1605 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1537
FT /note="H->A: Strongly reduced ability to repress
FT translation of target mRNAs."
FT /evidence="ECO:0000269|PubMed:19304925"
FT MUTAGEN 1543
FT /note="F->A: Weakly reduced ability to repress translation
FT of target mRNAs."
FT /evidence="ECO:0000269|PubMed:19304925"
FT MUTAGEN 1556
FT /note="Y->A: Strongly reduced ability to repress
FT translation of target mRNAs."
FT /evidence="ECO:0000269|PubMed:19304925"
FT MUTAGEN 1605
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1487, A-
FT 1494, A-1504, A-1515 and A-1648."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1647..1649
FT /note="LWG->AAA: Impairs interaction with the CCR4-NOT
FT complex, no effect on interaction with PABPC1; when
FT associated with 1658-A-A-1660."
FT MUTAGEN 1648
FT /note="W->A: Abolishes translational repression when
FT tethered to a target mRNA, abolishes association with the
FT CCR4-NOT complex; when associated with A-1445, A-1487, A-
FT 1494, A-1504, A-1515 and A-1605."
FT /evidence="ECO:0000269|PubMed:21984184"
FT MUTAGEN 1658..1660
FT /note="LWG->AAA: Impairs interaction with the CCR4-NOT
FT complex, no effect on interaction with PABPC1; when
FT associated with 1647-A-A-1649."
FT CONFLICT 728
FT /note="T -> S (in Ref. 6; AAH45631)"
FT /evidence="ECO:0000305"
FT CONFLICT 1231
FT /note="G -> C (in Ref. 6; AAH45631)"
FT /evidence="ECO:0000305"
FT CONFLICT 1555
FT /note="R -> P (in Ref. 6; AAH45631)"
FT /evidence="ECO:0000305"
FT HELIX 936..950
FT /evidence="ECO:0007829|PDB:2DKL"
FT HELIX 954..963
FT /evidence="ECO:0007829|PDB:2DKL"
FT HELIX 968..976
FT /evidence="ECO:0007829|PDB:2DKL"
SQ SEQUENCE 1690 AA; 175964 MW; C8230D65BFB1DA0B CRC64;
MATGSAQGNF TGHTKKTNGN NGTNGALVQS PSNQSALGAG GANSNGSAAR VWGVATGSSS
GLAHCSVSGG DGKMDTMIGD GRSQNCWGAS NSNAGINLNL NPNANPAAWP VLGHEGTVAT
GNPSSICSPV SAIGQNMGNQ NGNPTGTLGA WGNLLPQEST EPQTSTSQNV SFSAQPQNLN
TDGPNNTNPM NSSPNPINAM QTNGLPNWGM AVGMGAIIPP HLQGLPGANG SSVSQVSGGS
AEGISNSVWG LSPGNPATGN SNSGFSQGNG DTVNSALSAK QNGSSSAVQK EGSGGNAWDS
GPPAGPGILA WGRGSGNNGV GNIHSGAWGH PSRSTSNGVN GEWGKPPNQH SNSDINGKGS
TGWESPSVTS QNPTVQPGGE HMNSWAKAAS SGTTASEGSS DGSGNHNEGS TGREGTGEGR
RRDKGIIDQG HIQLPRNDLD PRVLSNTGWG QTPVKQNTAW EFEESPRSER KNDNGTEAWG
CAATQASNSG GKNDGSIMNS TNTSSVSGWV NAPPAAVPAN TGWGDSNNKA PSGPGVWGDS
ISSTAVSTAA AAKSGHAWSG AANQEDKSPT WGEPPKPKSQ HWGDGQRSNP AWSAGGGDWA
DSSSVLGHLG DGKKNGSGWD ADSNRSGSGW NDTTRSGNSG WGNSTNTKAN PGTNWGETLK
PGPQQNWASK PQDNNVSNWG GAASVKQTGT GWIGGPVPVK QKDSSEATGW EEPSPPSIRR
KMEIDDGTSA WGDPSNYNNK TVNMWDRNNP VIQSSTTTNT TTTTTTTTSN TTHRVETPPP
HQAGTQLNRS PLLGPGRKVS SGWGEMPNVH SKTENSWGEP SSPSTLVDNG TAAWGKPPSS
GSGWGDHPAE PPVAFGRAGA PVAASALCKP ASKSMQEGWG SGGDEMNLST SQWEDEEGDV
WNNAASQEST SSCSSWGNAP KKGLQKGMKT SGKQDEAWIM SRLIKQLTDM GFPREPAEEA
LKSNNMNLDQ AMSALLEKKV DVDKRGLGVT DHNGMAAKPL GCRPPISKES SVDRPTFLDK
DGGLVEEPTP SPFLPSPSLK LPLSHSALPS QALGGIASGL GMQNLNSSRQ IPSGNLGMFG
NSGAAQARTM QQPPQPPVQP LNSSQPSLRA QVPQFLSPQV QAQLLQFAAK NIGLNPALLT
SPINPQHMTM LNQLYQLQLA YQRLQIQQQM LQAQRNVSGS MRQQEQQVAR TITNLQQQIQ
QHQRQLAQAL LVKQPPPPPP PPHLSLHPSA GKSAMDSFPS HPQTPGLPDL QTKEQQSSPN
TFAPYPLAGL NPNMNVNSMD MTGGLSVKDP SQSQSRLPQW THPNSMDNLP SAASPLEQNP
SKHGAIPGGL SIGPPGKSSI DDSYGRYDLI QNSESPASPP VAVPHSWSRA KSDSDKISNG
SSINWPPEFH PGVPWKGLQN IDPENDPDVT PGSVPTGPTI NTTIQDVNRY LLKSGGKLSD
IKSTWSSGPT SHTQASLSHE LWKVPRNSTA PTRPPPGLTN PKPSSTWGAS PLGWTSSYSS
GSAWSTDTSG RTSSWLVLRN LTPQIDGSTL RTLCLQHGPL ITFHLNLTQG NAVVRYSSKE
EAAKAQKSLH MCVLGNTTIL AEFAGEEEVN RFLAQGQALP PTSSWQSSSA SSQPRLSAAG
SSHGLVRSDA GHWNAPCLGG KGSSELLWGG VPQYSSSLWG PPSADDSRVI GSPTPLTTLL
PGDLLSGESL
