TBL1R_HUMAN
ID TBL1R_HUMAN Reviewed; 514 AA.
AC Q9BZK7; D3DNQ9; Q14DC3; Q9H2I1; Q9H9A1;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=F-box-like/WD repeat-containing protein TBL1XR1;
DE AltName: Full=Nuclear receptor corepressor/HDAC3 complex subunit TBLR1;
DE AltName: Full=TBL1-related protein 1;
DE AltName: Full=Transducin beta-like 1X-related protein 1;
GN Name=TBL1XR1; Synonyms=IRA1, TBLR1;
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], IDENTIFICATION BY MASS SPECTROMETRY, AND
RP COMPONENT OF THE N-COR COMPLEX WITH NCOR1; NCOR2; GPS2; TBL1X 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11063877; DOI=10.1016/s0301-472x(00)00539-7;
RA Zhang X., Dormady S.P., Basch R.S.;
RT "Identification of four human cDNAs that are differentially expressed by
RT early hematopoietic progenitors.";
RL Exp. Hematol. 28:1286-1296(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal cortex, and Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP COMPONENT OF THE N-COR COMPLEX WITH TBL1X; 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 [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119, AND IDENTIFICATION BY
RP 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 [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [12]
RP INVOLVEMENT IN MRD41, AND VARIANT MRD41 PRO-282.
RX PubMed=22495309; DOI=10.1038/nature10989;
RA O'Roak B.J., Vives L., Girirajan S., Karakoc E., Krumm N., Coe B.P.,
RA Levy R., Ko A., Lee C., Smith J.D., Turner E.H., Stanaway I.B., Vernot B.,
RA Malig M., Baker C., Reilly B., Akey J.M., Borenstein E., Rieder M.J.,
RA Nickerson D.A., Bernier R., Shendure J., Eichler E.E.;
RT "Sporadic autism exomes reveal a highly interconnected protein network of
RT de novo mutations.";
RL Nature 485:246-250(2012).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP INVOLVEMENT IN MRD41.
RX PubMed=23160955; DOI=10.1126/science.1227764;
RA O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B., Phelps I.G.,
RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B.,
RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K.,
RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M.,
RA Bernier R., Eichler E.E., Shendure J.;
RT "Multiplex targeted sequencing identifies recurrently mutated genes in
RT autism spectrum disorders.";
RL Science 338:1619-1622(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 INVOLVEMENT IN MRD41, VARIANT MRD41 ASP-70, AND VARIANTS SER-116; GLU-405
RP AND SER-407.
RX PubMed=25102098; DOI=10.1038/jhg.2014.71;
RA Saitsu H., Tohyama J., Walsh T., Kato M., Kobayashi Y., Lee M.,
RA Tsurusaki Y., Miyake N., Goto Y., Nishino I., Ohtake A., King M.C.,
RA Matsumoto N.;
RT "A girl with West syndrome and autistic features harboring a de novo
RT TBL1XR1 mutation.";
RL J. Hum. Genet. 59:581-583(2014).
RN [17]
RP INVOLVEMENT IN MRD41, AND VARIANT MRD41 CYS-245.
RX PubMed=27133561; DOI=10.1002/ajmg.a.37684;
RG FORGE Canada Consortium;
RA Armour C.M., Smith A., Hartley T., Chardon J.W., Sawyer S.,
RA Schwartzentruber J., Hennekam R., Majewski J., Bulman D.E., Suri M.,
RA Boycott K.M.;
RT "Syndrome disintegration: Exome sequencing reveals that Fitzsimmons
RT syndrome is a co-occurrence of multiple events.";
RL Am. J. Med. Genet. A 170:1820-1825(2016).
RN [18]
RP TISSUE SPECIFICITY, INVOLVEMENT IN PRPTS, VARIANT PRPTS CYS-446, AND
RP CHARACTERIZATION OF VARIANT PRPTS CYS-446.
RX PubMed=26769062; DOI=10.1136/jmedgenet-2015-103233;
RA Heinen C.A., Jongejan A., Watson P.J., Redeker B., Boelen A.,
RA Boudzovitch-Surovtseva O., Forzano F., Hordijk R., Kelley R., Olney A.H.,
RA Pierpont M.E., Schaefer G.B., Stewart F., van Trotsenburg A.S., Fliers E.,
RA Schwabe J.W., Hennekam R.C.;
RT "A specific mutation in TBL1XR1 causes Pierpont syndrome.";
RL J. Med. Genet. 53:330-337(2016).
RN [19]
RP ERRATUM OF PUBMED:26769062.
RX PubMed=27221108; DOI=10.1136/jmedgenet-2015-103233corr1;
RA Heinen C.A., Jongejan A., Watson P.J., Redeker B., Boelen A.,
RA Boudzovitch-Surovtseva O., Forzano F., Hordijk R., Kelley R., Olney A.H.,
RA Pierpont M.E., Schaefer G.B., Stewart F., van Trotsenburg A.S., Fliers E.,
RA Schwabe J.W., Hennekam R.C.;
RL J. Med. Genet. 53:430-430(2016).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-277, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(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 the N-Cor corepressor complex that mediates the
CC recruitment of the 19S proteasome complex, leading to the subsequent
CC proteasomal degradation of N-Cor complex, thereby allowing cofactor
CC exchange, and transcription activation. {ECO:0000269|PubMed:14980219}.
CC -!- SUBUNIT: Component of the N-Cor repressor complex, at least composed of
CC NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2 (PubMed:11931768).
CC Probable component of some E3 ubiquitin ligase complex. Interacts with
CC histones H2B and H4 (PubMed:12628926). Interacts with MECP2; bridges
CC interaction between MECP2 and NCOR1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BHJ5, ECO:0000269|PubMed:11931768,
CC ECO:0000269|PubMed:12628926}.
CC -!- INTERACTION:
CC Q9BZK7; P36404: ARL2; NbExp=4; IntAct=EBI-765729, EBI-752365;
CC Q9BZK7; P54253: ATXN1; NbExp=6; IntAct=EBI-765729, EBI-930964;
CC Q9BZK7; O14645: DNALI1; NbExp=3; IntAct=EBI-765729, EBI-395638;
CC Q9BZK7; O14901: KLF11; NbExp=3; IntAct=EBI-765729, EBI-948266;
CC Q9BZK7; P00441: SOD1; NbExp=3; IntAct=EBI-765729, EBI-990792;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed including the pituitary,
CC hypothalamus, white and brown adipose tissue, muscle and liver.
CC {ECO:0000269|PubMed:26769062}.
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: Pierpont syndrome (PRPTS) [MIM:602342]: An autosomal dominant
CC syndrome characterized by multiple congenital anomalies, global
CC developmental delay, learning disability, palmar and plantar fat pads,
CC and distinctive facial characteristics, especially when smiling.
CC {ECO:0000269|PubMed:26769062}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 41
CC (MRD41) [MIM:616944]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRD41
CC patients manifest delayed psychomotor development, variable severity of
CC intellectual disability, and delayed language. Non-specific dysmorphic
CC features and autistic behavior is observed in some patients.
CC {ECO:0000269|PubMed:22495309, ECO:0000269|PubMed:23160955,
CC ECO:0000269|PubMed:25102098, ECO:0000269|PubMed:27133561}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the WD repeat EBI family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH60320.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AF314544; AAK00301.1; -; mRNA.
DR EMBL; AF268193; AAG44736.1; -; mRNA.
DR EMBL; AK022956; BAB14331.1; -; mRNA.
DR EMBL; CH471052; EAW78438.1; -; Genomic_DNA.
DR EMBL; BC060320; AAH60320.1; ALT_SEQ; mRNA.
DR EMBL; BC113421; AAI13422.1; -; mRNA.
DR CCDS; CCDS46961.1; -.
DR RefSeq; NP_001308122.1; NM_001321193.1.
DR RefSeq; NP_001308123.1; NM_001321194.1.
DR RefSeq; NP_001308124.1; NM_001321195.1.
DR RefSeq; NP_078941.2; NM_024665.5.
DR RefSeq; XP_005247832.1; XM_005247775.2.
DR RefSeq; XP_006713809.1; XM_006713746.1.
DR RefSeq; XP_011511443.1; XM_011513141.1.
DR RefSeq; XP_011511444.1; XM_011513142.2.
DR RefSeq; XP_011511445.1; XM_011513143.2.
DR RefSeq; XP_016862674.1; XM_017007185.1.
DR PDB; 4LG9; X-ray; 2.28 A; A=134-514.
DR PDBsum; 4LG9; -.
DR AlphaFoldDB; Q9BZK7; -.
DR SMR; Q9BZK7; -.
DR BioGRID; 122834; 169.
DR CORUM; Q9BZK7; -.
DR DIP; DIP-34582N; -.
DR IntAct; Q9BZK7; 57.
DR MINT; Q9BZK7; -.
DR STRING; 9606.ENSP00000405574; -.
DR GlyGen; Q9BZK7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BZK7; -.
DR PhosphoSitePlus; Q9BZK7; -.
DR BioMuta; TBL1XR1; -.
DR DMDM; 23396874; -.
DR EPD; Q9BZK7; -.
DR jPOST; Q9BZK7; -.
DR MassIVE; Q9BZK7; -.
DR MaxQB; Q9BZK7; -.
DR PaxDb; Q9BZK7; -.
DR PeptideAtlas; Q9BZK7; -.
DR PRIDE; Q9BZK7; -.
DR ProteomicsDB; 79864; -.
DR Antibodypedia; 9317; 368 antibodies from 33 providers.
DR DNASU; 79718; -.
DR Ensembl; ENST00000352800.10; ENSP00000263964.11; ENSG00000177565.18.
DR Ensembl; ENST00000422442.6; ENSP00000387849.3; ENSG00000177565.18.
DR Ensembl; ENST00000430069.5; ENSP00000405574.1; ENSG00000177565.18.
DR Ensembl; ENST00000457928.7; ENSP00000413251.3; ENSG00000177565.18.
DR Ensembl; ENST00000673974.1; ENSP00000501274.1; ENSG00000177565.18.
DR GeneID; 79718; -.
DR KEGG; hsa:79718; -.
DR MANE-Select; ENST00000457928.7; ENSP00000413251.3; NM_024665.7; NP_078941.2.
DR UCSC; uc003fiw.5; human.
DR CTD; 79718; -.
DR DisGeNET; 79718; -.
DR GeneCards; TBL1XR1; -.
DR HGNC; HGNC:29529; TBL1XR1.
DR HPA; ENSG00000177565; Low tissue specificity.
DR MalaCards; TBL1XR1; -.
DR MIM; 602342; phenotype.
DR MIM; 608628; gene.
DR MIM; 616944; phenotype.
DR neXtProt; NX_Q9BZK7; -.
DR OpenTargets; ENSG00000177565; -.
DR Orphanet; 520; Acute promyelocytic leukemia.
DR Orphanet; 487825; Pierpont syndrome.
DR PharmGKB; PA134928556; -.
DR VEuPathDB; HostDB:ENSG00000177565; -.
DR eggNOG; KOG0273; Eukaryota.
DR GeneTree; ENSGT00940000153421; -.
DR HOGENOM; CLU_007609_2_0_1; -.
DR InParanoid; Q9BZK7; -.
DR OMA; XTGALVH; -.
DR OrthoDB; 1463197at2759; -.
DR PhylomeDB; Q9BZK7; -.
DR TreeFam; TF323190; -.
DR PathwayCommons; Q9BZK7; -.
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; Q9BZK7; -.
DR SIGNOR; Q9BZK7; -.
DR BioGRID-ORCS; 79718; 221 hits in 1092 CRISPR screens.
DR ChiTaRS; TBL1XR1; human.
DR GeneWiki; TBL1XR1; -.
DR GenomeRNAi; 79718; -.
DR Pharos; Q9BZK7; Tbio.
DR PRO; PR:Q9BZK7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9BZK7; protein.
DR Bgee; ENSG00000177565; Expressed in calcaneal tendon and 203 other tissues.
DR ExpressionAtlas; Q9BZK7; baseline and differential.
DR Genevisible; Q9BZK7; 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:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus 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:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0060613; P:fat pad development; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0090207; P:regulation of triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl.
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; 2.
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; Chromatin regulator; Disease variant;
KW Intellectual disability; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway;
KW WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..514
FT /note="F-box-like/WD repeat-containing protein TBL1XR1"
FT /id="PRO_0000051266"
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 167..206
FT /note="WD 1"
FT REPEAT 223..262
FT /note="WD 2"
FT REPEAT 264..303
FT /note="WD 3"
FT REPEAT 306..344
FT /note="WD 4"
FT REPEAT 347..386
FT /note="WD 5"
FT REPEAT 389..437
FT /note="WD 6"
FT REPEAT 440..479
FT /note="WD 7"
FT REPEAT 481..513
FT /note="WD 8"
FT REGION 120..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BHJ5"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 277
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 70
FT /note="G -> D (in MRD41; dbSNP:rs786205859)"
FT /evidence="ECO:0000269|PubMed:25102098"
FT /id="VAR_076753"
FT VARIANT 116
FT /note="A -> S (in dbSNP:rs372813783)"
FT /evidence="ECO:0000269|PubMed:25102098"
FT /id="VAR_076754"
FT VARIANT 245
FT /note="Y -> C (in MRD41; dbSNP:rs878854401)"
FT /evidence="ECO:0000269|PubMed:27133561"
FT /id="VAR_076755"
FT VARIANT 282
FT /note="L -> P (in MRD41)"
FT /evidence="ECO:0000269|PubMed:22495309"
FT /id="VAR_076756"
FT VARIANT 405
FT /note="G -> E (found in a patient with epilepsy; unknown
FT pathological significance; dbSNP:rs747932785)"
FT /evidence="ECO:0000269|PubMed:25102098"
FT /id="VAR_076757"
FT VARIANT 407
FT /note="N -> S (found in a patient with epilepsy; unknown
FT pathological significance; dbSNP:rs781011308)"
FT /evidence="ECO:0000269|PubMed:25102098"
FT /id="VAR_076758"
FT VARIANT 446
FT /note="Y -> C (in PRPTS; does not affect assembly into the
FT N-Cor repressor complex; dbSNP:rs878854402)"
FT /evidence="ECO:0000269|PubMed:26769062"
FT /id="VAR_076759"
FT CONFLICT 31
FT /note="E -> K (in Ref. 2; AAG44736)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="Y -> H (in Ref. 3; BAB14331)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="A -> Q (in Ref. 2; AAG44736)"
FT /evidence="ECO:0000305"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 179..188
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 247..253
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 269..274
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 276..285
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4LG9"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 311..326
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 331..335
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 352..357
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 371..377
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 394..399
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 415..419
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 424..428
FT /evidence="ECO:0007829|PDB:4LG9"
FT TURN 429..432
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 433..438
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 445..450
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 454..461
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 464..470
FT /evidence="ECO:0007829|PDB:4LG9"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 486..491
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 495..502
FT /evidence="ECO:0007829|PDB:4LG9"
FT STRAND 507..511
FT /evidence="ECO:0007829|PDB:4LG9"
SQ SEQUENCE 514 AA; 55595 MW; 0B556D2EE4BA796D CRC64;
MSISSDEVNF LVYRYLQESG FSHSAFTFGI ESHISQSNIN GALVPPAALI SIIQKGLQYV
EAEVSINEDG TLFDGRPIES LSLIDAVMPD VVQTRQQAYR DKLAQQQAAA AAAAAAAASQ
QGSAKNGENT ANGEENGAHT IANNHTDMME VDGDVEIPPN KAVVLRGHES EVFICAWNPV
SDLLASGSGD STARIWNLSE NSTSGSTQLV LRHCIREGGQ DVPSNKDVTS LDWNSEGTLL
ATGSYDGFAR IWTKDGNLAS TLGQHKGPIF ALKWNKKGNF ILSAGVDKTT IIWDAHTGEA
KQQFPFHSAP ALDVDWQSNN TFASCSTDMC IHVCKLGQDR PIKTFQGHTN EVNAIKWDPT
GNLLASCSDD MTLKIWSMKQ DNCVHDLQAH NKEIYTIKWS PTGPGTNNPN ANLMLASASF
DSTVRLWDVD RGICIHTLTK HQEPVYSVAF SPDGRYLASG SFDKCVHIWN TQTGALVHSY
RGTGGIFEVC WNAAGDKVGA SASDGSVCVL DLRK
