TNR6B_HUMAN
ID TNR6B_HUMAN Reviewed; 1833 AA.
AC Q9UPQ9; B0QY73; B0QY78; B4DGC0; Q5TH52; Q8TBX2;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 4.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Trinucleotide repeat-containing gene 6B protein;
GN Name=TNRC6B; Synonyms=KIAA1093;
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 2).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
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 MRNA] (ISOFORM 1).
RC TISSUE=Amygdala;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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, FUNCTION, INTERACTION WITH AGO1 AND
RP AGO2, AND SUBCELLULAR LOCATION.
RX PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R.,
RA Tuschl T.;
RT "Identification of novel argonaute-associated proteins.";
RL Curr. Biol. 15:2149-2155(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH AGO1; AGO2; AGO3
RP AND AGO4.
RX PubMed=18690212; DOI=10.1038/nature07186;
RA Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y.,
RA Lee S.W., Peng J., Shi Y.;
RT "Prolyl 4-hydroxylation regulates Argonaute 2 stability.";
RL Nature 455:421-424(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1816, AND IDENTIFICATION BY
RP 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH AGO3 AND
RP AGO4, AND SUBCELLULAR LOCATION.
RX PubMed=19167051; DOI=10.1016/j.cell.2008.12.023;
RA Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P.,
RA Kremmer E., Benes V., Urlaub H., Meister G.;
RT "Importin 8 is a gene silencing factor that targets argonaute proteins to
RT distinct mRNAs.";
RL Cell 136:496-507(2009).
RN [11]
RP FUNCTION, AND INTERACTION WITH AGO2.
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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1816, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1816 AND SER-1832, AND
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
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 [17]
RP INTERACTION WITH CNOT1.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-879, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-879, 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-879, 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 [21]
RP INTERACTION WITH MOV10.
RX PubMed=24726324; DOI=10.1016/j.molcel.2014.03.017;
RA Gregersen L.H., Schueler M., Munschauer M., Mastrobuoni G., Chen W.,
RA Kempa S., Dieterich C., Landthaler M.;
RT "MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target
RT degradation by translocation along 3' UTRs.";
RL Mol. Cell 54:573-585(2014).
RN [22]
RP FUNCTION.
RX PubMed=32354837; DOI=10.1101/gad.336073.119;
RA Raesch F., Weber R., Izaurralde E., Igreja C.;
RT "4E-T-bound mRNAs are stored in a silenced and deadenylated form.";
RL Genes Dev. 34:847-860(2020).
RN [23]
RP INVOLVEMENT IN GDSBA, AND VARIANT GDSBA 680-TRP--ILE-1833 DEL.
RX PubMed=29463886; DOI=10.1038/s41380-018-0020-x;
RA Eising E., Carrion-Castillo A., Vino A., Strand E.A., Jakielski K.J.,
RA Scerri T.S., Hildebrand M.S., Webster R., Ma A., Mazoyer B., Francks C.,
RA Bahlo M., Scheffer I.E., Morgan A.T., Shriberg L.D., Fisher S.E.;
RT "A set of regulatory genes co-expressed in embryonic human brain is
RT implicated in disrupted speech development.";
RL Mol. Psychiatry 24:1065-1078(2019).
RN [24]
RP INVOLVEMENT IN GDSBA, AND VARIANTS GDSBA 627-GLN--ILE-1833 DEL;
RP 1115-ARG--ILE-1833 DEL; 1315-ARG--ILE-1833 DEL; 1323-GLN--ILE-1833 DEL AND
RP GLY-1357.
RX PubMed=32152250; DOI=10.1136/jmedgenet-2019-106470;
RA Granadillo J.L., Stegmann A.P.A., Guo H., Xia K., Angle B., Bontempo K.,
RA Ranells J.D., Newkirk P., Costin C., Viront J., Stumpel C.T., Sinnema M.,
RA Panis B., Pfundt R., Krapels I.P.C., Klaassens M., Nicolai J., Li J.,
RA Jiang Y., Marco E., Canton A., Latronico A.C., Montenegro L., Leheup B.,
RA Bonnet C., Amudhavalli S.M., Lawson C.E., McWalter K., Telegrafi A.,
RA Pearson R., Kvarnung M., Wang X., Bi W., Rosenfeld J.A., Shinawi M.;
RT "Pathogenic variants in TNRC6B cause a genetic disorder characterised by
RT developmental delay/intellectual disability and a spectrum of
RT neurobehavioural phenotypes including autism and ADHD.";
RL J. Med. Genet. 57:717-724(2020).
CC -!- FUNCTION: Plays a role in RNA-mediated gene silencing by both micro-
CC RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642,
CC PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-
CC dependent translational repression and siRNA-dependent endonucleolytic
CC cleavage of complementary mRNAs by argonaute family proteins
CC (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837).
CC As scaffolding protein associates with argonaute proteins bound to
CC partially complementary mRNAs and simultaneously can recruit CCR4-NOT
CC and PAN deadenylase complexes (PubMed:21981923).
CC {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051,
CC ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923,
CC ECO:0000269|PubMed:32354837}.
CC -!- SUBUNIT: Interacts with AGO1, AGO2, AGO3 and AGO4 (PubMed:16289642,
CC PubMed:18690212, PubMed:19167051, PubMed:19304925, PubMed:19383768).
CC Interacts with CNOT1; the interaction mediates the association with the
CC CCR4-NOT complex (PubMed:21981923, PubMed:21984185). Interacts with
CC PAN3; the interaction mediates the association with the PAN complex
CC (PubMed:21981923). Interacts with MOV10; the interaction is direct and
CC RNA-dependent (PubMed:24726324). {ECO:0000269|PubMed:16289642,
CC ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:19167051,
CC ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:19383768,
CC ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:21984185,
CC ECO:0000269|PubMed:24726324}.
CC -!- INTERACTION:
CC Q9UPQ9; Q9UKV8: AGO2; NbExp=13; IntAct=EBI-947158, EBI-528269;
CC Q9UPQ9; A5YKK6: CNOT1; NbExp=4; IntAct=EBI-947158, EBI-1222758;
CC Q9UPQ9; P11940: PABPC1; NbExp=3; IntAct=EBI-947158, EBI-81531;
CC Q9UPQ9; Q58A45: PAN3; NbExp=4; IntAct=EBI-947158, EBI-2513054;
CC Q9UPQ9; P21187: pAbp; Xeno; NbExp=6; IntAct=EBI-947158, EBI-103658;
CC Q9UPQ9-2; Q9UL18: AGO1; NbExp=4; IntAct=EBI-6514011, EBI-527363;
CC Q9UPQ9-2; Q9UKV8: AGO2; NbExp=4; IntAct=EBI-6514011, EBI-528269;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:16289642,
CC ECO:0000269|PubMed:19167051}. Note=Mammalian P-bodies are also known as
CC GW bodies (GWBs). {ECO:0000269|PubMed:16289642}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UPQ9-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPQ9-1; Sequence=VSP_037292, VSP_037293;
CC Name=3;
CC IsoId=Q9UPQ9-2; Sequence=VSP_037290, VSP_037291, VSP_037293;
CC -!- DISEASE: Global developmental delay with speech and behavioral
CC abnormalities (GDSBA) [MIM:619243]: An autosomal dominant disorder
CC manifesting in infancy or early childhood. It is characterized by
CC mildly delayed fine and motor skills, mildly impaired intellectual
CC development, speech and language delay, and variable behavioral
CC abnormalities, mostly autism and attention-deficit hyperactivity
CC disorder. Additional non-specific features include facial dysmorphism,
CC myopia or strabismus, and skeletal defects.
CC {ECO:0000269|PubMed:29463886, ECO:0000269|PubMed:32152250}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the GW182 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83045.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB029016; BAA83045.2; ALT_INIT; mRNA.
DR EMBL; AK294519; BAG57731.1; -; mRNA.
DR EMBL; Z93783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031589; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL022238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60367.1; -; Genomic_DNA.
DR EMBL; BC028626; AAH28626.1; -; mRNA.
DR CCDS; CCDS46712.1; -. [Q9UPQ9-2]
DR CCDS; CCDS46713.1; -. [Q9UPQ9-1]
DR CCDS; CCDS54533.1; -. [Q9UPQ9-3]
DR RefSeq; NP_001020014.1; NM_001024843.1. [Q9UPQ9-2]
DR RefSeq; NP_001155973.1; NM_001162501.1. [Q9UPQ9-3]
DR RefSeq; NP_055903.2; NM_015088.2. [Q9UPQ9-1]
DR AlphaFoldDB; Q9UPQ9; -.
DR SMR; Q9UPQ9; -.
DR BioGRID; 116735; 243.
DR DIP; DIP-29624N; -.
DR ELM; Q9UPQ9; -.
DR IntAct; Q9UPQ9; 88.
DR MINT; Q9UPQ9; -.
DR STRING; 9606.ENSP00000401946; -.
DR GlyGen; Q9UPQ9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPQ9; -.
DR PhosphoSitePlus; Q9UPQ9; -.
DR BioMuta; TNRC6B; -.
DR DMDM; 229904901; -.
DR EPD; Q9UPQ9; -.
DR jPOST; Q9UPQ9; -.
DR MassIVE; Q9UPQ9; -.
DR MaxQB; Q9UPQ9; -.
DR PaxDb; Q9UPQ9; -.
DR PeptideAtlas; Q9UPQ9; -.
DR PRIDE; Q9UPQ9; -.
DR ProteomicsDB; 85420; -. [Q9UPQ9-3]
DR ProteomicsDB; 85421; -. [Q9UPQ9-1]
DR ProteomicsDB; 85422; -. [Q9UPQ9-2]
DR Antibodypedia; 294; 105 antibodies from 21 providers.
DR DNASU; 23112; -.
DR Ensembl; ENST00000301923.13; ENSP00000306759.9; ENSG00000100354.21. [Q9UPQ9-2]
DR Ensembl; ENST00000335727.13; ENSP00000338371.8; ENSG00000100354.21. [Q9UPQ9-1]
DR Ensembl; ENST00000402203.5; ENSP00000384795.1; ENSG00000100354.21. [Q9UPQ9-2]
DR Ensembl; ENST00000454349.7; ENSP00000401946.2; ENSG00000100354.21. [Q9UPQ9-3]
DR GeneID; 23112; -.
DR KEGG; hsa:23112; -.
DR MANE-Select; ENST00000454349.7; ENSP00000401946.2; NM_001162501.2; NP_001155973.1.
DR UCSC; uc003aym.4; human. [Q9UPQ9-3]
DR CTD; 23112; -.
DR DisGeNET; 23112; -.
DR GeneCards; TNRC6B; -.
DR HGNC; HGNC:29190; TNRC6B.
DR HPA; ENSG00000100354; Low tissue specificity.
DR MalaCards; TNRC6B; -.
DR MIM; 610740; gene.
DR MIM; 619243; phenotype.
DR neXtProt; NX_Q9UPQ9; -.
DR OpenTargets; ENSG00000100354; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA134992981; -.
DR VEuPathDB; HostDB:ENSG00000100354; -.
DR eggNOG; ENOG502QQIH; Eukaryota.
DR GeneTree; ENSGT00940000155813; -.
DR HOGENOM; CLU_001298_2_0_1; -.
DR InParanoid; Q9UPQ9; -.
DR OMA; NASWPPX; -.
DR OrthoDB; 50428at2759; -.
DR PhylomeDB; Q9UPQ9; -.
DR TreeFam; TF329702; -.
DR PathwayCommons; Q9UPQ9; -.
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; Q9UPQ9; -.
DR BioGRID-ORCS; 23112; 19 hits in 1083 CRISPR screens.
DR ChiTaRS; TNRC6B; human.
DR GeneWiki; TNRC6B; -.
DR GenomeRNAi; 23112; -.
DR Pharos; Q9UPQ9; Tbio.
DR PRO; PR:Q9UPQ9; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9UPQ9; protein.
DR Bgee; ENSG00000100354; Expressed in buccal mucosa cell and 208 other tissues.
DR ExpressionAtlas; Q9UPQ9; baseline and differential.
DR Genevisible; Q9UPQ9; 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; HDA:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IMP:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; IBA:GO_Central.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB.
DR CDD; cd12712; RRM_TNRC6B; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR019486; Argonaute_hook_dom.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR032226; TNRC6_PABC-bd.
DR InterPro; IPR033500; TNRC6B.
DR InterPro; IPR034925; TNRC6B_RRM.
DR PANTHER; PTHR13020:SF32; PTHR13020:SF32; 1.
DR Pfam; PF10427; Ago_hook; 1.
DR Pfam; PF16608; TNRC6-PABC_bdg; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autism spectrum disorder; Coiled coil; Cytoplasm;
KW Disease variant; Intellectual disability; Phosphoprotein;
KW Reference proteome; RNA-binding; RNA-mediated gene silencing;
KW Translation regulation.
FT CHAIN 1..1833
FT /note="Trinucleotide repeat-containing gene 6B protein"
FT /id="PRO_0000072605"
FT DOMAIN 1648..1720
FT /note="RRM"
FT REGION 1..994
FT /note="Interaction with argonaute proteins"
FT REGION 1..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..1046
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1193..1212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1218..1723
FT /note="Silencing domain; interaction with CNOT1 and PAN3"
FT /evidence="ECO:0000269|PubMed:21981923"
FT REGION 1316..1346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1472..1490
FT /note="PABPC1-interacting motif-2 (PAM2)"
FT REGION 1590..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1730..1763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1809..1833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1..39
FT /evidence="ECO:0000255"
FT COMPBIAS 1..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..164
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 205..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 367..389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..450
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..589
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..632
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 634..650
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..771
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 807..823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 824..852
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 896..913
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 926..956
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 970..996
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1020..1042
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1316..1334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1610..1638
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1744..1760
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 879
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BKI2"
FT MOD_RES 1449
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BKI2"
FT MOD_RES 1461
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BKI2"
FT MOD_RES 1464
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BKI2"
FT MOD_RES 1816
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 1832
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..2
FT /note="MR -> MQTNEGEVSEESSSKVEQEDFVMEGHGKTPPPGEESKQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037290"
FT VAR_SEQ 153..935
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037291"
FT VAR_SEQ 936..989
FT /note="VWSKSTPPAPDNGTSAWGEPNESSPGWGEMDDTGASTTGWGNTPANAPNAMK
FT PN -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851"
FT /id="VSP_037292"
FT VAR_SEQ 1138..1194
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037293"
FT VARIANT 517
FT /note="S -> C (in dbSNP:rs17001767)"
FT /id="VAR_051452"
FT VARIANT 627..1833
FT /note="Missing (in GDSBA)"
FT /evidence="ECO:0000269|PubMed:32152250"
FT /id="VAR_085412"
FT VARIANT 680..1833
FT /note="Missing (in GDSBA)"
FT /evidence="ECO:0000269|PubMed:29463886"
FT /id="VAR_081535"
FT VARIANT 1115..1833
FT /note="Missing (in GDSBA)"
FT /evidence="ECO:0000269|PubMed:32152250"
FT /id="VAR_085413"
FT VARIANT 1315..1833
FT /note="Missing (in GDSBA)"
FT /evidence="ECO:0000269|PubMed:32152250"
FT /id="VAR_085414"
FT VARIANT 1323..1833
FT /note="Missing (in GDSBA)"
FT /evidence="ECO:0000269|PubMed:32152250"
FT /id="VAR_085415"
FT VARIANT 1357
FT /note="V -> G (in GDSBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32152250"
FT /id="VAR_085416"
FT CONFLICT 1321
FT /note="Missing (in Ref. 1; BAA83045)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1833 AA; 194002 MW; E982B786C97C75D0 CRC64;
MREKEQEREE QLMEDKKRKK EDKKKKEATQ KVTEQKTKVP EVTKPSLSQP TAASPIGSSP
SPPVNGGNNA KRVAVPNGQP PSAARYMPRE VPPRFRCQQD HKVLLKRGQP PPPSCMLLGG
GAGPPPCTAP GANPNNAQVT GALLQSESGT APDSTLGGAA ASNYANSTWG SGASSNNGTS
PNPIHIWDKV IVDGSDMEEW PCIASKDTES SSENTTDNNS ASNPGSEKST LPGSTTSNKG
KGSQCQSASS GNECNLGVWK SDPKAKSVQS SNSTTENNNG LGNWRNVSGQ DRIGPGSGFS
NFNPNSNPSA WPALVQEGTS RKGALETDNS NSSAQVSTVG QTSREQQSKM ENAGVNFVVS
GREQAQIHNT DGPKNGNTNS LNLSSPNPME NKGMPFGMGL GNTSRSTDAP SQSTGDRKTG
SVGSWGAARG PSGTDTVSGQ SNSGNNGNNG KEREDSWKGA SVQKSTGSKN DSWDNNNRST
GGSWNFGPQD SNDNKWGEGN KMTSGVSQGE WKQPTGSDEL KIGEWSGPNQ PNSSTGAWDN
QKGHPLPENQ GNAQAPCWGR SSSSTGSEVG GQSTGSNHKA GSSDSHNSGR RSYRPTHPDC
QAVLQTLLSR TDLDPRVLSN TGWGQTQIKQ DTVWDIEEVP RPEGKSDKGT EGWESAATQT
KNSGGWGDAP SQSNQMKSGW GELSASTEWK DPKNTGGWND YKNNNSSNWG GGRPDEKTPS
SWNENPSKDQ GWGGGRQPNQ GWSSGKNGWG EEVDQTKNSN WESSASKPVS GWGEGGQNEI
GTWGNGGNAS LASKGGWEDC KRSPAWNETG RQPNSWNKQH QQQQPPQQPP PPQPEASGSW
GGPPPPPPGN VRPSNSSWSS GPQPATPKDE EPSGWEEPSP QSISRKMDID DGTSAWGDPN
SYNYKNVNLW DKNSQGGPAP REPNLPTPMT SKSASVWSKS TPPAPDNGTS AWGEPNESSP
GWGEMDDTGA STTGWGNTPA NAPNAMKPNS KSMQDGWGES DGPVTGARHP SWEEEEDGGV
WNTTGSQGSA SSHNSASWGQ GGKKQMKCSL KGGNNDSWMN PLAKQFSNMG LLSQTEDNPS
SKMDLSVGSL SDKKFDVDKR AMNLGDFNDI MRKDRSGFRP PNSKDMGTTD SGPYFEKLTL
PFSNQDGCLG DEAPCSPFSP SPSYKLSPSG STLPNVSLGA IGTGLNPQNF AARQGGSHGL
FGNSTAQSRG LHTPVQPLNS SPSLRAQVPP QFISPQVSAS MLKQFPNSGL SPGLFNVGPQ
LSPQQIAMLS QLPQIPQFQL ACQLLLQQQQ QQQLLQNQRK ISQAVRQQQE QQLARMVSAL
QQQQQQQQRQ PGMKHSPSHP VGPKPHLDNM VPNALNVGLP DLQTKGPIPG YGSGFSSGGM
DYGMVGGKEA GTESRFKQWT SMMEGLPSVA TQEANMHKNG AIVAPGKTRG GSPYNQFDII
PGDTLGGHTG PAGDSWLPAK SPPTNKIGSK SSNASWPPEF QPGVPWKGIQ NIDPESDPYV
TPGSVLGGTA TSPIVDTDHQ LLRDNTTGSN SSLNTSLPSP GAWPYSASDN SFTNVHSTSA
KFPDYKSTWS PDPIGHNPTH LSNKMWKNHI SSRNTTPLPR PPPGLTNPKP SSPWSSTAPR
SVRGWGTQDS RLASASTWSD GGSVRPSYWL VLHNLTPQID GSTLRTICMQ HGPLLTFHLN
LTQGTALIRY STKQEAAKAQ TALHMCVLGN TTILAEFATD DEVSRFLAQA QPPTPAATPS
APAAGWQSLE TGQNQSDPVG PALNLFGGST GLGQWSSSAG GSSGADLAGA SLWGPPNYSS
SLWGVPTVED PHRMGSPAPL LPGDLLGGGS DSI
