TBL1X_MOUSE
ID TBL1X_MOUSE Reviewed; 527 AA.
AC Q9QXE7; Q8BMM0; Q8BYQ4; Q8C0A1;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=F-box-like/WD repeat-containing protein TBL1X;
DE AltName: Full=Transducin beta-like protein 1X;
GN Name=Tbl1x; Synonyms=Tbl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus, Medulla oblongata, and Pituitary;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 200-527.
RC STRAIN=129/SvJ;
RA Botcherby M.R.M., Straw R., Clarke D., Greystrong J.S., Weston P.,
RA Hunter G., Kimberly C., Rhodes M.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH GPS2.
RX PubMed=26070566; DOI=10.1074/jbc.m115.637660;
RA Huang J., Cardamone M.D., Johnson H.E., Neault M., Chan M., Floyd Z.E.,
RA Mallette F.A., Perissi V.;
RT "Exchange factor TBL1 and arginine methyltransferase PRMT6 cooperate in
RT protecting G protein pathway suppressor 2 (GPS2) from proteasomal
RT degradation.";
RL J. Biol. Chem. 290:19044-19054(2015).
RN [7]
RP MUTAGENESIS OF GLU-184; ASP-326; GLU-364; ASP-382; PRO-457 AND TYR-459,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MECP2.
RX PubMed=28348241; DOI=10.1073/pnas.1700731114;
RA Kruusvee V., Lyst M.J., Taylor C., Tarnauskaite Z., Bird A.P., Cook A.G.;
RT "Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett
RT syndrome and related disorders.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E3243-E3250(2017).
CC -!- FUNCTION: F-box-like protein involved in the recruitment of the
CC ubiquitin/19S proteasome complex to nuclear receptor-regulated
CC transcription units. Plays an essential role in transcription
CC activation mediated by nuclear receptors. Probably acts as integral
CC component of corepressor complexes that mediates the recruitment of the
CC 19S proteasome complex, leading to the subsequent proteasomal
CC degradation of transcription repressor complexes, thereby allowing
CC cofactor exchange (By similarity). {ECO:0000250|UniProtKB:O60907}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers (By similarity). Component of
CC the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3,
CC TBL1X, TBL1R, CORO2A and GPS2. Component of a E3 ubiquitin ligase
CC complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X.
CC Interacts with GPS2 (when sumoylated); leading to protect GPS2 against
CC degradation by the proteasome (PubMed:26070566). Probably part of other
CC corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts
CC with histones H2B, H3a and H4 (By similarity). Interacts with MECP2;
CC recruits TBL1X to the heterochromatin foci (PubMed:28348241).
CC {ECO:0000250|UniProtKB:O60907, ECO:0000269|PubMed:26070566,
CC ECO:0000269|PubMed:28348241}.
CC -!- INTERACTION:
CC Q9QXE7; P51608: MECP2; Xeno; NbExp=3; IntAct=EBI-8821270, EBI-1189067;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Colocalized with
CC MECP2 to the heterochromatin foci. {ECO:0000269|PubMed:28348241}.
CC -!- TISSUE SPECIFICITY: Expressed in the cochlea.
CC {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 -!- SIMILARITY: Belongs to the WD repeat EBI family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB61534.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK030547; BAC27015.1; -; mRNA.
DR EMBL; AK031937; BAC27612.1; -; mRNA.
DR EMBL; AK038674; BAC30092.1; -; mRNA.
DR EMBL; BC043105; AAH43105.1; -; mRNA.
DR EMBL; F38006; CAB61534.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS41036.1; -.
DR RefSeq; NP_065626.1; NM_020601.2.
DR RefSeq; XP_006528002.1; XM_006527939.2.
DR AlphaFoldDB; Q9QXE7; -.
DR SMR; Q9QXE7; -.
DR BioGRID; 203977; 13.
DR DIP; DIP-62055N; -.
DR IntAct; Q9QXE7; 3.
DR MINT; Q9QXE7; -.
DR STRING; 10090.ENSMUSP00000085549; -.
DR iPTMnet; Q9QXE7; -.
DR PhosphoSitePlus; Q9QXE7; -.
DR EPD; Q9QXE7; -.
DR MaxQB; Q9QXE7; -.
DR PaxDb; Q9QXE7; -.
DR PeptideAtlas; Q9QXE7; -.
DR PRIDE; Q9QXE7; -.
DR ProteomicsDB; 262952; -.
DR DNASU; 21372; -.
DR Ensembl; ENSMUST00000088217; ENSMUSP00000085549; ENSMUSG00000025246.
DR GeneID; 21372; -.
DR KEGG; mmu:21372; -.
DR UCSC; uc009tqo.1; mouse.
DR CTD; 6907; -.
DR MGI; MGI:1336172; Tbl1x.
DR VEuPathDB; HostDB:ENSMUSG00000025246; -.
DR eggNOG; KOG0273; Eukaryota.
DR GeneTree; ENSGT00940000153421; -.
DR HOGENOM; CLU_007609_2_0_1; -.
DR InParanoid; Q9QXE7; -.
DR OMA; KWNKCGN; -.
DR OrthoDB; 1463197at2759; -.
DR PhylomeDB; Q9QXE7; -.
DR TreeFam; TF323190; -.
DR Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR Reactome; R-MMU-350054; Notch-HLH transcription pathway.
DR Reactome; R-MMU-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-MMU-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR BioGRID-ORCS; 21372; 8 hits in 77 CRISPR screens.
DR ChiTaRS; Tbl1x; mouse.
DR PRO; PR:Q9QXE7; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9QXE7; protein.
DR Bgee; ENSMUSG00000025246; Expressed in embryonic post-anal tail and 237 other tissues.
DR Genevisible; Q9QXE7; MM.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0043627; P:response to estrogen; IMP:MGI.
DR GO; GO:0048545; P:response to steroid hormone; IMP:MGI.
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; 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 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 Acetylation; Activator; Isopeptide bond; Nucleus; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT CHAIN 2..527
FT /note="F-box-like/WD repeat-containing protein TBL1X"
FT /id="PRO_0000051265"
FT DOMAIN 4..36
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 41..86
FT /note="F-box-like"
FT REPEAT 180..219
FT /note="WD 1"
FT REPEAT 236..275
FT /note="WD 2"
FT REPEAT 277..316
FT /note="WD 3"
FT REPEAT 319..359
FT /note="WD 4"
FT REPEAT 360..399
FT /note="WD 5"
FT REPEAT 402..450
FT /note="WD 6"
FT REPEAT 453..492
FT /note="WD 7"
FT REPEAT 494..526
FT /note="WD 8"
FT REGION 127..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BHJ5"
FT CROSSLNK 290
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BZK7"
FT MUTAGEN 184
FT /note="E->A: Affects recruitment to heterochromatin by
FT MECP2."
FT /evidence="ECO:0000269|PubMed:28348241"
FT MUTAGEN 326
FT /note="D->N: Affects recruitment to heterochromatin by
FT MECP2."
FT /evidence="ECO:0000269|PubMed:28348241"
FT MUTAGEN 364
FT /note="E->A: Affects recruitment to heterochromatin by
FT MECP2."
FT /evidence="ECO:0000269|PubMed:28348241"
FT MUTAGEN 382
FT /note="D->A: Affects recruitment to heterochromatin by
FT MECP2. Does not interact with MECP2. Is efficiently
FT incorporated in N-Cor repressor complex."
FT /evidence="ECO:0000269|PubMed:28348241"
FT MUTAGEN 457
FT /note="P->R: Does not interact with MECP2. Affects
FT recruitment to heterochromatin by MECP2. Is efficiently
FT incorporated in N-Cor repressor complex."
FT /evidence="ECO:0000269|PubMed:28348241"
FT MUTAGEN 459
FT /note="Y->F: Does not affect recruitment to heterochromatin
FT by MECP2."
FT /evidence="ECO:0000269|PubMed:28348241"
FT CONFLICT 104
FT /note="A -> T (in Ref. 1; BAC27015)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="L -> H (in Ref. 1; BAC27612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 527 AA; 56802 MW; 146435A9C51DFDA6 CRC64;
MSITSDEVNF LVYRYLQESG FSHSAFTFGI ESHISQSNIN GTLVPPAALI SILQKGLQYV
EAEISINEDG TVFDGRPIES LSLIDAVMPD VVQTRQQAFR EKLAQQQANA AAAAAAAAAT
ATSTAATTPA AAAQQNPPKN GEATVNGEEN GAHAINNHSK PMEIDGDVEI PPSKATVLRG
HESEVFICAW NPVSDLLASG SGDSTARIWN LNENSNGGST QLVLRHCIRE GGHDVPSNKD
VTSLDWNSDG TLLATGSYDG FARIWTEDGN LASTLGQHKG PIFALKWNKK GNYILSAGVD
KTTIIWDAHT GEAKQQFPFH SAPALDVDWQ NNTTFASCST DMCIHVCRLG CDRPVKTFQG
HTNEVNAIKW DPSGMLLASC SDDMTLKIWS MKQDACVHDL QAHSKEIYTI KWSPTGPATS
NPNSNIMLAS ASFDSTVRLW DVERGVCIHT LTKHQEPVYS VAFSPDGKYL ASGSFDKCVH
IWNTQSGSLV HSYRGTGGIF EVCWNARGDK VGASASDGSV CVLDLRK
