THRAP3 (thyroid hormone receptor associated protein 3)

2012-03-01   Kuo-Ming Lee , Woan-Yuh Tarn 

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Identity

HGNC
LOCATION
1p34.3
LOCUSID
ALIAS
BCLAF2,TRAP150
FUSION GENES

DNA/RNA

Description

The THRAP3 gene contains 12 exons with the size of 80942 bases.

Transcription

This gene has 4 transcripts (according to Ensembl).

Pseudogene

3 pseudogene are found (Review record(s) in Gene).

Proteins

Description

TRAP150 contains an arginine/serine (RS)-rich sequence in the N-terminal region, while its C-terminal region has 48% overall identity with BCLAF1, a cell death-promoting transcriptional repressor bcl2-associated factor (Ito et al., 1999; Kasof et al., 1999). Notably, BCLAF1 also contains an RS domain in the N-terminus. Based on the high similarity between TRAP150 and BCLAF1, these two proteins constitute a gene family. Within the BCLAF1 homologous domain of TRAP150, a segment of ~90 amino acids shares 30% similarity with MLN51, which is a core component of the exon juction complex (Macchi et al., 2003). Biochemical identification of proteins with phosphorylated residues has revealed that TRAP150 is likely phosphorylated protein (Beausoleil et al., 2004; Beausoleil et al., 2006; Olsen et al., 2006; Matsuoka et al.,2007; Molina et al., 2007).

Expression

Ubiquitous.

Localisation

TRAP150 is primarily localized in the nucleoplasm and accumulated in some punctuate foci, albeit excluded from the nucleoli. The speckled structures of TRAP150 are colocalized with the splicing factor SC35. Using the heterokaryon assay, TRAP150 was demonstrated to be a nuclear-restricted protein, while it is associated with the mRNA export receptor TAP (Lee et al., 2010). The mouse TRAP150, like its human homolog, was also detected in nuclear speckles, especially, under transcription-inhibition conditions (Sutherland et al., 2001).

Function

Transcription
TRAP150 was initially identified as a subunit of the TRAP (thyroid hormone receptor associated protein)/Mediator complex (Ito et al., 1999). Moreover, it was also detected in a group of proteins that were associated with the tail of histone H3 and H4 (Choi et al., 2007; Heo et al., 2007). However, whether TRAP150 participates in the transcription regulation is poorly documented.

Splicing
TRAP150 contains an RS domain and is associated with several precursor mRNA (pre-mRNA) splicing factors (Li et al., 2003; Lee et al., 2010). Moreover, TRAP150 was also reported to interact with the domains that provide links between transcription and splicing, such as the WW domains of pinin and the FF domains of CA150 (Smith et al., 2004; Ingham et al., 2005). Therefore TRAP150 has been proposed to function in coupling of transcription and pre-mRNA processing (Auboeuf et al., 2005). This possibility was supported by independent biochemical analyses of mRNA ribonucleoprotein (mRNP) complexes. Firstly, TRAP150 was identified as a component of mRNPs; its association with mRNAs was splicing- and cap-binding complex (CBC)-independent (Merz et al., 2007). Moreover, TRAP150 was detected in the spliceosomal complex B, which is a fully assembled splicing complex prior to the catalytic step of splicing (Bessonov et al., 2008; Wahl et al., 2009). Finally, experimental evidence showed that overexpression of TRAP150 activated the splicing of a reporter pre-mRNA, while knockdown of TRAP150 impaired the splicing (Lee et al., 2010), indicating the role of TRAP150 in facilitating pre-mRNA splicing.

Other pre-mRNA processing events
TRAP150 and its analog BCLAF1 are associated with SNIP1 (Smad nuclear interacting protein 1), pinin and SkIP (Ski-interacting protein) to form the SNIP1/SkIP-associated RNA processing (SNARP) complex. The SNARP regulates the expression level of cyclin D1 probably by recruiting U2AF65 to its pre-mRNA (Bracken et al., 2008; Witzel et al., 2010).
To date, whether TRAP150 is directly involved in alternative pre-mRNA splicing still remains to be investigated. However, TRAP150 may modulate splicing through protein-protein interactions. In resting T cells, TRAP150 binds to phosphorylated PTB-associated splicing factor (PSF), which results in steric hindrance of the RNA recognition motifs of PSF. Upon T cell activation, de-phosphorylated PSF is dissociated from TRAP150 and therfore could regulate the alternative splicing of CD45 transcripts (Heyd et al., 2010).
In addition to splicing, TRAP150 may participate in mRNA degradation. When tethered to a reporter precursor mRNA, TRAP150 could promote the degradation of the spliced mRNA, which occurs in a translation-independent manner and in the nucleus (Lee et al., 2010).

Homology

Homologous genes of TRAP150 are found in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish (homologs of the THRAP3 gene).

Bibliography

Pubmed IDLast YearTitleAuthors
159647892005A subset of nuclear receptor coregulators act as coupling proteins during synthesis and maturation of RNA transcripts.Auboeuf D et al
169642432006A probability-based approach for high-throughput protein phosphorylation analysis and site localization.Beausoleil SA et al
183224602008Isolation of an active step I spliceosome and composition of its RNP core.Bessonov S et al
187941512008Regulation of cyclin D1 RNA stability by SNIP1.Bracken CP et al
175483432007Purification and characterization of cellular proteins associated with histone H4 tails.Choi J et al
174036662007Isolation and characterization of proteins associated with histone H3 tails in vivo.Heo K et al
209324802010Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing.Heyd F et al
160557202005WW domains provide a platform for the assembly of multiprotein networks.Ingham RJ et al
101986381999Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.Ito M et al
103301791999Btf, a novel death-promoting transcriptional repressor that interacts with Bcl-2-related proteins.Kasof GM et al
201237362010TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.Lee KM et al
145599932003Regulation of alternative splicing by SRrp86 and its interacting proteins.Li J et al
128432822003Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in an RNA-dependent manner.Macchi P et al
175253322007ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.Matsuoka S et al
170955402007Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment.Merz C et al
172873402007Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.Molina H et al
170819832006Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.Olsen JV et al
154858972004FF domains of CA150 bind transcription and splicing factors through multiple weak interactions.Smith MJ et al
115556362001Large-scale identification of mammalian proteins localized to nuclear sub-compartments.Sutherland HG et al
192398902009The spliceosome: design principles of a dynamic RNP machine.Wahl MC et al
200740632010Regulation of cyclin D1 gene expression.Witzel II et al

Other Information

Locus ID:

NCBI: 9967
MIM: 603809
HGNC: 22964
Ensembl: ENSG00000054118

Variants:

dbSNP: 9967
ClinVar: 9967
TCGA: ENSG00000054118
COSMIC: THRAP3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000054118ENST00000354618Q9Y2W1
ENSG00000054118ENST00000469141Q9Y2W1
ENSG00000054118ENST00000648638A0A3B3ITZ9

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
MetabolismREACTOMER-HSA-1430728
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Fatty acid, triacylglycerol, and ketone body metabolismREACTOMER-HSA-535734
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)REACTOMER-HSA-400206
PPARA activates gene expressionREACTOMER-HSA-1989781
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
224247732012Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.129
240553472013Proteome-wide identification of poly(ADP-Ribosyl)ation targets in different genotoxic stress responses.120
121305442002TFIID and human mediator coactivator complexes assemble cooperatively on promoter DNA.47
253166752014Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming.18
291127142017The RNA processing factors THRAP3 and BCLAF1 promote the DNA damage response through selective mRNA splicing and nuclear export.16
235252312013THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation.12
237785352013Btf and TRAP150 have distinct roles in regulating subcellular mRNA distribution.12
262612102015TRAP150 interacts with the RNA-binding domain of PSF and antagonizes splicing of numerous PSF-target genes in T cells.9
287703542018THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis.0

Citation

Kuo-Ming Lee ; Woan-Yuh Tarn

THRAP3 (thyroid hormone receptor associated protein 3)

Atlas Genet Cytogenet Oncol Haematol. 2012-03-01

Online version: http://atlasgeneticsoncology.org/gene/42960/thrap3