TBL1X_HUMAN
ID TBL1X_HUMAN Reviewed; 577 AA.
AC O60907; A8K044; A8K4J7; Q86UY2;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=F-box-like/WD repeat-containing protein TBL1X;
DE AltName: Full=SMAP55;
DE AltName: Full=Transducin beta-like protein 1X;
DE AltName: Full=Transducin-beta-like protein 1, X-linked;
GN Name=TBL1X; Synonyms=TBL1;
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), AND TISSUE SPECIFICITY.
RX PubMed=10330347; DOI=10.1086/302408;
RA Bassi M.T., Ramesar R.S., Caciotti B., Winship I.M., De Grandi A.,
RA Riboni M., Townes P.L., Beighton P., Ballabio A., Borsani G.;
RT "X-linked late-onset sensorineural deafness caused by a deletion involving
RT OA1 and a novel gene containing WD-40 repeats.";
RL Am. J. Hum. Genet. 64:1604-1616(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lymph, and Pancreas;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND COMPONENT OF THE N-COR COMPLEX
RP WITH NCOR2 AND HDAC3.
RX PubMed=10809664;
RA Guenther M.G., Lane W.S., Fischle W., Verdin E., Lazar M.A.,
RA Shiekhattar R.;
RT "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat
RT protein linked to deafness.";
RL Genes Dev. 14:1048-1057(2000).
RN [6]
RP COMPONENT OF THE N-COR COMPLEX WITH NCOR2 AND HDAC3.
RX PubMed=10944117; DOI=10.1093/emboj/19.16.4342;
RA Li J., Wang J., Wang J., Nawaz Z., Liu J.M., Qin J., Wong J.;
RT "Both corepressor proteins SMRT and N-CoR exist in large protein complexes
RT containing HDAC3.";
RL EMBO J. 19:4342-4350(2000).
RN [7]
RP SUBUNIT OF A COMPLEX WITH UBE2D1; CACYBP; SIAH1 AND APC.
RX PubMed=11389839; DOI=10.1016/s1097-2765(01)00242-8;
RA Matsuzawa S., Reed J.C.;
RT "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin
RT degradation linked to p53 responses.";
RL Mol. Cell 7:915-926(2001).
RN [8]
RP COMPONENT OF THE N-COR COMPLEX WITH NCOR1; NCOR2; GPS2; TBL1R AND HDAC3.
RX PubMed=11931768; DOI=10.1016/s1097-2765(02)00468-9;
RA Zhang J., Kalkum M., Chait B.T., Roeder R.G.;
RT "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK
RT pathway through the integral subunit GPS2.";
RL Mol. Cell 9:611-623(2002).
RN [9]
RP COMPONENT OF THE N-COR COMPLEX WITH TBL1R; CORO2A AND HDAC3, AND
RP HISTONE-BINDING.
RX PubMed=12628926; DOI=10.1093/emboj/cdg120;
RA Yoon H.-G., Chan D.W., Huang Z.-Q., Li J., Fondell J.D., Qin J., Wong J.;
RT "Purification and functional characterization of the human N-CoR complex:
RT the roles of HDAC3, TBL1 and TBLR1.";
RL EMBO J. 22:1336-1346(2003).
RN [10]
RP FUNCTION, AND RECRUITMENT OF 19S PROTEASOME COMPLEX.
RX PubMed=14980219; DOI=10.1016/s0092-8674(04)00133-3;
RA Perissi V., Aggarwal A., Glass C.K., Rose D.W., Rosenfeld M.G.;
RT "A corepressor/coactivator exchange complex required for transcriptional
RT activation by nuclear receptors and other regulated transcription
RT factors.";
RL Cell 116:511-526(2004).
RN [11]
RP INTERACTION WITH GPS2.
RX PubMed=24943844; DOI=10.1091/mbc.e13-12-0733;
RA Bi H., Li S., Wang M., Jia Z., Chang A.K., Pang P., Wu H.;
RT "SUMOylation of GPS2 protein regulates its transcription-suppressing
RT function.";
RL Mol. Biol. Cell 25:2499-2508(2014).
RN [12]
RP INVOLVEMENT IN CHNG8, VARIANTS CHNG8 TYR-416; THR-417; ARG-420; TYR-504 AND
RP CYS-509, AND CHARACTERIZATION OF VARIANTS CHNG8 TYR-416; THR-417; TYR-504
RP AND CYS-509.
RX PubMed=27603907; DOI=10.1210/jc.2016-2531;
RA Heinen C.A., Losekoot M., Sun Y., Watson P.J., Fairall L., Joustra S.D.,
RA Zwaveling-Soonawala N., Oostdijk W., van den Akker E.L., Alders M.,
RA Santen G.W., van Rijn R.R., Dreschler W.A., Surovtseva O.V., Biermasz N.R.,
RA Hennekam R.C., Wit J.M., Schwabe J.W., Boelen A., Fliers E.,
RA van Trotsenburg A.S.;
RT "Mutations in TBL1X are associated with central hypothyroidism.";
RL J. Clin. Endocrinol. Metab. 101:4564-4573(2016).
RN [13]
RP INVOLVEMENT IN CHNG8, AND VARIANT CHNG8 339-ARG--LYS-577 DEL.
RX PubMed=30591955; DOI=10.1210/js.2018-00144;
RA Garcia M., Barreda-Bonis A.C., Jimenez P., Rabanal I., Ortiz A.,
RA Vallespin E., Del Pozo A., Martinez-San Millan J., Gonzalez-Casado I.,
RA Moreno J.C.;
RT "Central hypothyroidism and novel clinical phenotypes in hemizygous
RT truncation of TBL1X.";
RL J. Endocr. Soc. 3:119-128(2019).
RN [14] {ECO:0007744|PDB:2XTC, ECO:0007744|PDB:2XTD, ECO:0007744|PDB:2XTE}
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 52-141, FUNCTION, SUBUNIT,
RP IDENTIFICATION IN THE N-COR COMPLEX, AND MUTAGENESIS OF PHE-77; ILE-90;
RP LEU-94; PRO-96; LEU-108; VAL-111 AND ILE-117.
RX PubMed=21240272; DOI=10.1038/nsmb.1983;
RA Oberoi J., Fairall L., Watson P.J., Yang J.C., Czimmerer Z., Kampmann T.,
RA Goult B.T., Greenwood J.A., Gooch J.T., Kallenberger B.C., Nagy L.,
RA Neuhaus D., Schwabe J.W.;
RT "Structural basis for the assembly of the SMRT/NCoR core transcriptional
RT repression machinery.";
RL Nat. Struct. Mol. Biol. 18:177-184(2011).
CC -!- FUNCTION: F-box-like protein involved in the recruitment of the
CC ubiquitin/19S proteasome complex to nuclear receptor-regulated
CC transcription units (PubMed:14980219). Plays an essential role in
CC transcription activation mediated by nuclear receptors. Probably acts
CC as integral component of corepressor complexes that mediates the
CC recruitment of the 19S proteasome complex, leading to the subsequent
CC proteasomal degradation of transcription repressor complexes, thereby
CC allowing cofactor exchange (PubMed:21240272).
CC {ECO:0000269|PubMed:14980219, ECO:0000269|PubMed:21240272}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers (PubMed:21240272). Component of
CC the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3,
CC TBL1X, TBL1R, CORO2A and GPS2 (PubMed:10809664, PubMed:21240272).
CC Interacts with GPS2 (when sumoylated); leading to protect GPS2 against
CC degradation by the proteasome (PubMed:24943844). Component of a E3
CC ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1,
CC APC and TBL1X (PubMed:11389839). Probably part of other corepressor
CC complexes, that do not contain NCOR1 and NCOR2. Interacts with histones
CC H2B, H3a and H4. Interacts with MECP2; recruits TBL1X to the
CC heterochromatin foci (By similarity). {ECO:0000250|UniProtKB:Q9QXE7,
CC ECO:0000269|PubMed:10809664, ECO:0000269|PubMed:11389839,
CC ECO:0000269|PubMed:21240272, ECO:0000269|PubMed:24943844}.
CC -!- INTERACTION:
CC O60907; P36405: ARL3; NbExp=3; IntAct=EBI-3505105, EBI-712710;
CC O60907; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-3505105, EBI-717399;
CC O60907-2; P25685: DNAJB1; NbExp=3; IntAct=EBI-15904933, EBI-357034;
CC O60907-2; Q13227: GPS2; NbExp=6; IntAct=EBI-15904933, EBI-713355;
CC O60907-2; O14901: KLF11; NbExp=3; IntAct=EBI-15904933, EBI-948266;
CC O60907-2; A0A024RBS3: NCOR2; NbExp=7; IntAct=EBI-15904933, EBI-15904969;
CC O60907-2; O60907-2: TBL1X; NbExp=2; IntAct=EBI-15904933, EBI-15904933;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Colocalized with
CC MECP2 to the heterochromatin foci. {ECO:0000250|UniProtKB:Q9QXE7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60907-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60907-2; Sequence=VSP_036905;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10330347}.
CC -!- DOMAIN: The F-box-like domain is related to the F-box domain, and
CC apparently displays the same function as component of ubiquitin E3
CC ligase complexes. {ECO:0000250}.
CC -!- DISEASE: Hypothyroidism, congenital, non-goitrous, 8 (CHNG8)
CC [MIM:301033]: A form of central hypothyroidism, a disorder
CC characterized by sub-optimal thyroid hormone secretion, due to
CC insufficient stimulation by the thyroid stimulating hormone of an
CC otherwise normal thyroid gland. It may be caused by congenital or
CC acquired disorders of the pituitary gland or hypothalamus. CHNG8 is a
CC congenital, X-linked, relatively mild form which may be accompanied by
CC hearing loss in some patients. {ECO:0000269|PubMed:27603907,
CC ECO:0000269|PubMed:30591955}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat EBI family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y12781; CAA73319.1; -; mRNA.
DR EMBL; AK289409; BAF82098.1; -; mRNA.
DR EMBL; AK290962; BAF83651.1; -; mRNA.
DR EMBL; AC003036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032708; AAH32708.1; -; mRNA.
DR EMBL; BC052304; AAH52304.1; -; mRNA.
DR CCDS; CCDS14133.1; -. [O60907-1]
DR CCDS; CCDS48078.1; -. [O60907-2]
DR RefSeq; NP_001132938.1; NM_001139466.1. [O60907-1]
DR RefSeq; NP_001132939.1; NM_001139467.1. [O60907-2]
DR RefSeq; NP_001132940.1; NM_001139468.1. [O60907-2]
DR RefSeq; NP_005638.1; NM_005647.3. [O60907-1]
DR RefSeq; XP_011543873.1; XM_011545571.2.
DR PDB; 2XTC; X-ray; 2.22 A; A/B=52-141.
DR PDB; 2XTD; X-ray; 3.20 A; A/B=52-122.
DR PDB; 2XTE; X-ray; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L=52-141.
DR PDBsum; 2XTC; -.
DR PDBsum; 2XTD; -.
DR PDBsum; 2XTE; -.
DR AlphaFoldDB; O60907; -.
DR SMR; O60907; -.
DR BioGRID; 112770; 131.
DR CORUM; O60907; -.
DR DIP; DIP-60532N; -.
DR IntAct; O60907; 67.
DR MINT; O60907; -.
DR STRING; 9606.ENSP00000217964; -.
DR GlyGen; O60907; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60907; -.
DR PhosphoSitePlus; O60907; -.
DR BioMuta; TBL1X; -.
DR EPD; O60907; -.
DR jPOST; O60907; -.
DR MassIVE; O60907; -.
DR MaxQB; O60907; -.
DR PaxDb; O60907; -.
DR PeptideAtlas; O60907; -.
DR PRIDE; O60907; -.
DR ProteomicsDB; 49664; -. [O60907-1]
DR ProteomicsDB; 49665; -. [O60907-2]
DR ABCD; O60907; 6 sequenced antibodies.
DR Antibodypedia; 3946; 234 antibodies from 36 providers.
DR DNASU; 6907; -.
DR Ensembl; ENST00000380961.5; ENSP00000370348.1; ENSG00000101849.18. [O60907-2]
DR Ensembl; ENST00000407597.7; ENSP00000385988.2; ENSG00000101849.18. [O60907-1]
DR Ensembl; ENST00000424279.6; ENSP00000394097.1; ENSG00000101849.18. [O60907-2]
DR Ensembl; ENST00000645353.2; ENSP00000496215.1; ENSG00000101849.18. [O60907-1]
DR Ensembl; ENST00000645686.1; ENSP00000493782.1; ENSG00000101849.18. [O60907-1]
DR Ensembl; ENST00000646640.1; ENSP00000495556.1; ENSG00000101849.18. [O60907-1]
DR GeneID; 6907; -.
DR KEGG; hsa:6907; -.
DR MANE-Select; ENST00000645353.2; ENSP00000496215.1; NM_005647.4; NP_005638.1.
DR UCSC; uc004csq.5; human. [O60907-1]
DR CTD; 6907; -.
DR DisGeNET; 6907; -.
DR GeneCards; TBL1X; -.
DR HGNC; HGNC:11585; TBL1X.
DR HPA; ENSG00000101849; Low tissue specificity.
DR MalaCards; TBL1X; -.
DR MIM; 300196; gene.
DR MIM; 301033; phenotype.
DR neXtProt; NX_O60907; -.
DR OpenTargets; ENSG00000101849; -.
DR PharmGKB; PA36349; -.
DR VEuPathDB; HostDB:ENSG00000101849; -.
DR eggNOG; KOG0273; Eukaryota.
DR GeneTree; ENSGT00940000153421; -.
DR HOGENOM; CLU_007609_2_0_1; -.
DR InParanoid; O60907; -.
DR OMA; KWNKCGN; -.
DR PhylomeDB; O60907; -.
DR TreeFam; TF323190; -.
DR PathwayCommons; O60907; -.
DR Reactome; R-HSA-1368082; RORA activates gene expression.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-9022537; Loss of MECP2 binding ability to the NCoR/SMRT complex.
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 Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; O60907; -.
DR BioGRID-ORCS; 6907; 11 hits in 710 CRISPR screens.
DR ChiTaRS; TBL1X; human.
DR EvolutionaryTrace; O60907; -.
DR GeneWiki; TBL1X; -.
DR GenomeRNAi; 6907; -.
DR Pharos; O60907; Tbio.
DR PRO; PR:O60907; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O60907; protein.
DR Bgee; ENSG00000101849; Expressed in cauda epididymis and 197 other tissues.
DR ExpressionAtlas; O60907; baseline and differential.
DR Genevisible; O60907; HS.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR045183; Ebi-like.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR22846; PTHR22846; 1.
DR Pfam; PF08513; LisH; 1.
DR Pfam; PF00400; WD40; 6.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00667; LisH; 1.
DR SMART; SM00320; WD40; 8.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Congenital hypothyroidism; Deafness; Disease variant; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway;
KW WD repeat.
FT CHAIN 1..577
FT /note="F-box-like/WD repeat-containing protein TBL1X"
FT /id="PRO_0000051263"
FT DOMAIN 55..87
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 92..137
FT /note="F-box-like"
FT REPEAT 230..269
FT /note="WD 1"
FT REPEAT 286..325
FT /note="WD 2"
FT REPEAT 327..366
FT /note="WD 3"
FT REPEAT 369..409
FT /note="WD 4"
FT REPEAT 410..449
FT /note="WD 5"
FT REPEAT 452..500
FT /note="WD 6"
FT REPEAT 503..542
FT /note="WD 7"
FT REPEAT 544..576
FT /note="WD 8"
FT REGION 177..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..193
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 153
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BHJ5"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT CROSSLNK 340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_036905"
FT VARIANT 339..577
FT /note="Missing (in CHNG8)"
FT /evidence="ECO:0000269|PubMed:30591955"
FT /id="VAR_083285"
FT VARIANT 416
FT /note="N -> Y (in CHNG8; unknown pathological significance;
FT decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:27603907"
FT /id="VAR_083286"
FT VARIANT 417
FT /note="A -> T (in CHNG8; unknown pathological significance;
FT no effect on protein expression)"
FT /evidence="ECO:0000269|PubMed:27603907"
FT /id="VAR_083287"
FT VARIANT 420
FT /note="W -> R (in CHNG8; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27603907"
FT /id="VAR_083288"
FT VARIANT 504
FT /note="H -> Y (in CHNG8; unknown pathological significance;
FT decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:27603907"
FT /id="VAR_083289"
FT VARIANT 509
FT /note="Y -> C (in CHNG8; unknown pathological significance;
FT no effect on protein expression)"
FT /evidence="ECO:0000269|PubMed:27603907"
FT /id="VAR_083290"
FT MUTAGEN 77
FT /note="F->A: Abolished homotetramerization, leading to a
FT homodimer."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 90
FT /note="I->A: Reduced interaction with NCOR2 and GPS2."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 94
FT /note="L->A,E: Does not affect interaction with NCOR2 and
FT GPS2."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 96
FT /note="P->G: Does not affect interaction with NCOR2 and
FT GPS2."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 108
FT /note="L->A,Q: Reduced interaction with NCOR2 and GPS2."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 111
FT /note="V->N,Q: Reduced interaction with NCOR2 and GPS2.
FT Abolished ability to repress transcription."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 117
FT /note="I->A: Does not affect interaction with NCOR2 and
FT GPS2."
FT /evidence="ECO:0000269|PubMed:21240272"
FT CONFLICT 316
FT /note="T -> A (in Ref. 2; BAF82098)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="T -> A (in Ref. 2; BAF83651)"
FT /evidence="ECO:0000305"
FT HELIX 56..69
FT /evidence="ECO:0007829|PDB:2XTC"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:2XTC"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:2XTC"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:2XTC"
FT HELIX 99..116
FT /evidence="ECO:0007829|PDB:2XTC"
SQ SEQUENCE 577 AA; 62496 MW; D830A37781E2A15C CRC64;
MTELAGASSS CCHRPAGRGA MQSVLHHFQR LRGREGGSHF INTSSPRGEA KMSITSDEVN
FLVYRYLQES GFSHSAFTFG IESHISQSNI NGTLVPPAAL ISILQKGLQY VEAEISINED
GTVFDGRPIE SLSLIDAVMP DVVQTRQQAF REKLAQQQAS AAAAAAAATA AATAATTTSA
GVSHQNPSKN REATVNGEEN RAHSVNNHAK PMEIDGEVEI PSSKATVLRG HESEVFICAW
NPVSDLLASG SGDSTARIWN LNENSNGGST QLVLRHCIRE GGHDVPSNKD VTSLDWNTNG
TLLATGSYDG FARIWTEDGN LASTLGQHKG PIFALKWNRK GNYILSAGVD KTTIIWDAHT
GEAKQQFPFH SAPALDVDWQ NNTTFASCST DMCIHVCRLG CDRPVKTFQG HTNEVNAIKW
DPSGMLLASC SDDMTLKIWS MKQEVCIHDL QAHNKEIYTI KWSPTGPATS NPNSNIMLAS
ASFDSTVRLW DIERGVCTHT LTKHQEPVYS VAFSPDGKYL ASGSFDKCVH IWNTQSGNLV
HSYRGTGGIF EVCWNARGDK VGASASDGSV CVLDLRK
