TBL1XR1

F-box-like/WD repeat-containing protein TBL1XR1 is a protein that in humans is encoded by the TBL1XR1 gene.[5][6][7] The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins that appear to have a regulatory function. It is believed that the WD40 repeats mediate protein–protein interactions, and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation.[7]

TBL1XR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4LG9
Identifiers
Aliases	TBL1XR1, C21, DC42, IRA1, TBLR1, MRD41, transducin (beta)-like 1 X-linked receptor 1, transducin beta like 1 X-linked receptor 1, TBL1X receptor 1
External IDs	OMIM: 608628 MGI: 2441730 HomoloGene: 69382 GeneCards: TBL1XR1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q26.32 Start 177,019,340 bp[1] End 177,228,000 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 A3 Start 22,076,652 bp[2] End 22,216,594 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • beta-catenin binding • GO:0001106 transcription corepressor activity • protein N-terminus binding • histone binding • GO:0001948 protein binding Cellular component • histone deacetylase complex • transcriptional repressor complex • nucleoplasm • spindle microtubule • cell nucleus • mitotic spindle Biological process • fat pad development • response to dietary excess • regulation of transcription, DNA-templated • multicellular organism growth • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • positive regulation of transcription, DNA-templated • lipid catabolic process • regulation of triglyceride metabolic process • white fat cell differentiation • regulation of gene expression • adipose tissue development • negative regulation of transcription, DNA-templated • histone deacetylation • positive regulation of transcription from RNA polymerase II promoter • proteasome-mediated ubiquitin-dependent protein catabolic process • regulation of lipid metabolic process • positive regulation of canonical Wnt signaling pathway • chromatin organization • blastocyst hatching • regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79718	81004
Ensembl	ENSG00000177565	ENSMUSG00000027630
UniProt	Q9BZK7	Q8BHJ5
RefSeq (mRNA)	NM_024665 NM_001321193 NM_001321194 NM_001321195 NM_001374327 NM_001374328 NM_001374329 NM_001374330	NM_030732
RefSeq (protein)	NP_001308122 NP_001308123 NP_001308124 NP_078941 NP_001361256 NP_001361257 NP_001361258 NP_001361259	NP_109657
Location (UCSC)	Chr 3: 177.02 – 177.23 Mb	Chr 3: 22.08 – 22.22 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

Mutations in TBL1XR1 cause Pierpont syndrome, which involves intellectual disability, a characteristic facial appearance and limb abnormalities.[8]

Mutations in TBL1XR1 have been identified in lymphomas, including MYD88 wild-type Waldenstrom's macroglobulinemia.[9]

In prostate cancer, somatic copy-number gains (CNA) in TBL1XR1 are present in around 15% of patients with localised disease, co-occurring with adjacent megagene NAALADL2.[10] The frequency of CNA gains in these genes associate with a number of clinical features of aggressive prostate cancer including high Gleason grade, tumour stage, positive surgical margins and cancer which has spread to the lymph nodes.[10] The frequency of copy-number gains in this genetic region also increase in castrate resistant and neuroendocrine prostate cancer.[10]

The region surrounding TBL1XR1 is rich in oncogenes.[11] Copy-number gains in TBL1XR1 often co-occur with neighbouring oncogenes including: BCL6, ATR and PI3K family members. Copy-number gains at the DNA level associate with mRNA expression changes in more than 450 known oncogenes, suggesting this region may be important in driving aggressive prostate cancer.[10] TBL1XR1 is a co-activator of the androgen receptor, a major hormone receptor driving prostate cancer development.[12] Of the genes whose expression was altered between patients with and without gains, 506 (14.09%) of the genes were androgen-regulated or contained an AR binding site.[10]

Interactions

TBL1XR1 has been shown to interact with nuclear receptor co-repressor 1.[6][13][14]

References

1. GRCh38: Ensembl release 89: ENSG00000177565 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027630 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Zhang X, Dormady SP, Basch RS (November 2000). "Identification of four human cDNAs that are differentially expressed by early hematopoietic progenitors". Experimental Hematology. 28 (11): 1286–96. doi:10.1016/S0301-472X(00)00539-7. PMID 11063877.
6. Zhang J, Kalkum M, Chait BT, Roeder RG (March 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Molecular Cell. 9 (3): 611–23. doi:10.1016/S1097-2765(02)00468-9. PMID 11931768.
7. "Entrez Gene: TBL1XR1 transducin (beta)-like 1X-linked receptor 1".
8. "OMIM Entry - # 602342 - PIERPONT SYNDROME; PRPTS". www.omim.org. Retrieved 2020-04-05.
9. Hunter Z, Tsakmaklis N, Demos M, Kofides A, Xu L, Chan G, et al. (2017). "The Genomic Landscape of MYD88 Wild-Type Waldenström's Macroglobulinemia is Characterized by Somatic Mutations in TBL1XR1, the CBM Complex, and NFKB2" (PDF). Blood. 130 (Supplement 1): 130. doi:10.1182/blood.V130.Suppl_1.4011.4011 (inactive 2021-01-13).CS1 maint: DOI inactive as of January 2021 (link)
10. Simpson BS, Camacho N, Luxton HJ, Pye H, Finn R, Heavey S, et al. (August 2020). "Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype". Communications Biology. 3 (1): 440. doi:10.1038/s42003-020-01175-x. PMC 7429505. PMID 32796921.
11. Fields AP, Justilien V, Murray NR (January 2016). "The chromosome 3q26 OncCassette: A multigenic driver of human cancer". Advances in Biological Regulation. 60: 47–63. doi:10.1016/j.jbior.2015.10.009. PMC 4729592. PMID 26754874.
12. Daniels G, Li Y, Gellert LL, Zhou A, Melamed J, Wu X, et al. (February 2014). "TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth". Endocrine-Related Cancer. 21 (1): 127–42. doi:10.1530/ERC-13-0293. PMC 3947037. PMID 24243687.
13. Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (September 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell. 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
14. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (March 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal. 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.

Further reading

• Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (March 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal. 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.
• Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (September 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell. 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
• Perissi V, Aggarwal A, Glass CK, Rose DW, Rosenfeld MG (February 2004). "A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors". Cell. 116 (4): 511–26. doi:10.1016/S0092-8674(04)00133-3. PMID 14980219. S2CID 18807923.
• Yoon HG, Choi Y, Cole PA, Wong J (January 2005). "Reading and function of a histone code involved in targeting corepressor complexes for repression". Molecular and Cellular Biology. 25 (1): 324–35. doi:10.1128/MCB.25.1.324-335.2005. PMC 538779. PMID 15601853.
• Zhang XM, Chang Q, Zeng L, Gu J, Brown S, Basch RS (August 2006). "TBLR1 regulates the expression of nuclear hormone receptor co-repressors". BMC Cell Biology. 7: 31. doi:10.1186/1471-2121-7-31. PMC 1555579. PMID 16893456.
• Liu Y, Sun W, Zhang K, Zheng H, Ma Y, Lin D, et al. (June 2007). "Identification of genes differentially expressed in human primary lung squamous cell carcinoma". Lung Cancer. 56 (3): 307–17. doi:10.1016/j.lungcan.2007.01.016. PMID 17316888.