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THRAP3 (thyroid hormone receptor associated protein 3)

Written2012-03Kuo-Ming Lee, Woan-Yuh Tarn
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)TRAP150
Other alias
HGNC (Hugo) THRAP3
LocusID (NCBI) 9967
Atlas_Id 42960
Location 1p34.3  [Link to chromosome band 1p34]
Location_base_pair Starts at 36224412 and ends at 36305356 bp from pter ( according to hg19-Feb_2009)  [Mapping THRAP3.png]
Local_order See NCBI and Ensembl.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CYP19A1 (15q21.2) / THRAP3 (1p34.3)PDHX (11p13) / THRAP3 (1p34.3)THRAP3 (1p34.3) / AGO3 (1p34.3)
THRAP3 (1p34.3) / CAPZB (1p36.13)THRAP3 (1p34.3) / KIAA0319L (1p34.3)THRAP3 (1p34.3) / MALAT1 (11q13.1)
THRAP3 (1p34.3) / MAP7D1 (1p34.3)THRAP3 (1p34.3) / MUTYH (1p34.1)THRAP3 (1p34.3) / SH3BP2 (4p16.3)
THRAP3 (1p34.3) / TBC1D2B (15q24.3)THRAP3 (1p34.3) / USP6 (17p13.2)USP6 (17p13.2) / THRAP3 (1p34.3)

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).

Protein

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).

Implicated in

Note
Note See t(1;17)(p34;p13) in aneurysmal bone cyst.
  

Bibliography

A subset of nuclear receptor coregulators act as coupling proteins during synthesis and maturation of RNA transcripts.
Auboeuf D, Dowhan DH, Dutertre M, Martin N, Berget SM, O'Malley BW. (REVIEW)
Mol Cell Biol. 2005 Jul;25(13):5307-16.
PMID 15964789
 
A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP.
Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10.
PMID 16964243
 
Isolation of an active step I spliceosome and composition of its RNP core.
Bessonov S, Anokhina M, Will CL, Urlaub H, Luhrmann R.
Nature. 2008 Apr 17;452(7189):846-50. Epub 2008 Mar 5.
PMID 18322460
 
Regulation of cyclin D1 RNA stability by SNIP1.
Bracken CP, Wall SJ, Barre B, Panov KI, Ajuh PM, Perkins ND.
Cancer Res. 2008 Sep 15;68(18):7621-8.
PMID 18794151
 
Purification and characterization of cellular proteins associated with histone H4 tails.
Choi J, Kim B, Heo K, Kim K, Kim H, Zhan Y, Ranish JA, An W.
J Biol Chem. 2007 Jul 20;282(29):21024-31. Epub 2007 Jun 4.
PMID 17548343
 
Isolation and characterization of proteins associated with histone H3 tails in vivo.
Heo K, Kim B, Kim K, Choi J, Kim H, Zhan Y, Ranish JA, An W.
J Biol Chem. 2007 May 25;282(21):15476-83. Epub 2007 Apr 1.
PMID 17403666
 
Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing.
Heyd F, Lynch KW.
Mol Cell. 2010 Oct 8;40(1):126-37.
PMID 20932480
 
WW domains provide a platform for the assembly of multiprotein networks.
Ingham RJ, Colwill K, Howard C, Dettwiler S, Lim CS, Yu J, Hersi K, Raaijmakers J, Gish G, Mbamalu G, Taylor L, Yeung B, Vassilovski G, Amin M, Chen F, Matskova L, Winberg G, Ernberg I, Linding R, O'donnell P, Starostine A, Keller W, Metalnikov P, Stark C, Pawson T.
Mol Cell Biol. 2005 Aug;25(16):7092-106.
PMID 16055720
 
Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.
Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG.
Mol Cell. 1999 Mar;3(3):361-70.
PMID 10198638
 
Btf, a novel death-promoting transcriptional repressor that interacts with Bcl-2-related proteins.
Kasof GM, Goyal L, White E.
Mol Cell Biol. 1999 Jun;19(6):4390-404.
PMID 10330179
 
TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.
Lee KM, Hsu IaW, Tarn WY.
Nucleic Acids Res. 2010 Jun;38(10):3340-50. Epub 2010 Jan 31.
PMID 20123736
 
Regulation of alternative splicing by SRrp86 and its interacting proteins.
Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG.
Mol Cell Biol. 2003 Nov;23(21):7437-47.
PMID 14559993
 
Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in an RNA-dependent manner.
Macchi P, Kroening S, Palacios IM, Baldassa S, Grunewald B, Ambrosino C, Goetze B, Lupas A, St Johnston D, Kiebler M.
J Neurosci. 2003 Jul 2;23(13):5778-88.
PMID 12843282
 
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ.
Science. 2007 May 25;316(5828):1160-6.
PMID 17525332
 
Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment.
Merz C, Urlaub H, Will CL, Luhrmann R.
RNA. 2007 Jan;13(1):116-28. Epub 2006 Nov 9.
PMID 17095540
 
Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.
Molina H, Horn DM, Tang N, Mathivanan S, Pandey A.
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2199-204. Epub 2007 Feb 7.
PMID 17287340
 
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M.
Cell. 2006 Nov 3;127(3):635-48.
PMID 17081983
 
FF domains of CA150 bind transcription and splicing factors through multiple weak interactions.
Smith MJ, Kulkarni S, Pawson T.
Mol Cell Biol. 2004 Nov;24(21):9274-85.
PMID 15485897
 
Large-scale identification of mammalian proteins localized to nuclear sub-compartments.
Sutherland HG, Mumford GK, Newton K, Ford LV, Farrall R, Dellaire G, Caceres JF, Bickmore WA.
Hum Mol Genet. 2001 Sep 1;10(18):1995-2011.
PMID 11555636
 
The spliceosome: design principles of a dynamic RNP machine.
Wahl MC, Will CL, Luhrmann R.
Cell. 2009 Feb 20;136(4):701-18. (REVIEW)
PMID 19239890
 
Regulation of cyclin D1 gene expression.
Witzel II, Koh LF, Perkins ND.
Biochem Soc Trans. 2010 Feb;38(Pt 1):217-22. (REVIEW)
PMID 20074063
 

Citation

This paper should be referenced as such :
Lee, KM ; Tarn, WY
THRAP3 (thyroid hormone receptor associated protein 3)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):626-628.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/THRAP3ID42960ch1p34.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Bone: Aneurysmal bone cysts
Bone: Aneurysmal bone cyst with t(1;17)(p34;p13) THRAP3/USP6


External links

Nomenclature
HGNC (Hugo)THRAP3   22964
Cards
AtlasTHRAP3ID42960ch1p34
Entrez_Gene (NCBI)THRAP3  9967  thyroid hormone receptor associated protein 3
AliasesTRAP150
GeneCards (Weizmann)THRAP3
Ensembl hg19 (Hinxton)ENSG00000054118 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000054118 [Gene_View]  chr1:36224412-36305356 [Contig_View]  THRAP3 [Vega]
ICGC DataPortalENSG00000054118
TCGA cBioPortalTHRAP3
AceView (NCBI)THRAP3
Genatlas (Paris)THRAP3
WikiGenes9967
SOURCE (Princeton)THRAP3
Genetics Home Reference (NIH)THRAP3
Genomic and cartography
GoldenPath hg38 (UCSC)THRAP3  -     chr1:36224412-36305356 +  1p34.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)THRAP3  -     1p34.3   [Description]    (hg19-Feb_2009)
EnsemblTHRAP3 - 1p34.3 [CytoView hg19]  THRAP3 - 1p34.3 [CytoView hg38]
Mapping of homologs : NCBITHRAP3 [Mapview hg19]  THRAP3 [Mapview hg38]
OMIM603809   
Gene and transcription
Genbank (Entrez)AF117756 AI754117 AK025408 AK025735 BC002501
RefSeq transcript (Entrez)NM_001321471 NM_001321473 NM_005119
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)THRAP3
Cluster EST : UnigeneHs.744057 [ NCBI ]
CGAP (NCI)Hs.744057
Alternative Splicing GalleryENSG00000054118
Gene ExpressionTHRAP3 [ NCBI-GEO ]   THRAP3 [ EBI - ARRAY_EXPRESS ]   THRAP3 [ SEEK ]   THRAP3 [ MEM ]
Gene Expression Viewer (FireBrowse)THRAP3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9967
GTEX Portal (Tissue expression)THRAP3
Human Protein AtlasENSG00000054118-THRAP3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y2W1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y2W1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y2W1
Splice isoforms : SwissVarQ9Y2W1
PhosPhoSitePlusQ9Y2W1
Domains : Interpro (EBI)THRAP3    THRAP3_BCLAF1   
Domain families : Pfam (Sanger)THRAP3_BCLAF1 (PF15440)   
Domain families : Pfam (NCBI)pfam15440   
Conserved Domain (NCBI)THRAP3
DMDM Disease mutations9967
Blocks (Seattle)THRAP3
SuperfamilyQ9Y2W1
Human Protein Atlas [tissue]ENSG00000054118-THRAP3 [tissue]
Peptide AtlasQ9Y2W1
HPRD07543
IPIIPI00104050   IPI00977867   
Protein Interaction databases
DIP (DOE-UCLA)Q9Y2W1
IntAct (EBI)Q9Y2W1
FunCoupENSG00000054118
BioGRIDTHRAP3
STRING (EMBL)THRAP3
ZODIACTHRAP3
Ontologies - Pathways
QuickGOQ9Y2W1
Ontology : AmiGOregulation of alternative mRNA splicing, via spliceosome  nuclear-transcribed mRNA catabolic process  core promoter sequence-specific DNA binding  RNA polymerase II transcription cofactor activity  transcription cofactor activity  transcription coactivator activity  RNA binding  receptor activity  protein binding  ATP binding  nucleus  nucleoplasm  transcription initiation from RNA polymerase II promoter  mRNA processing  circadian rhythm  RNA splicing  mediator complex  nuclear speck  ligand-dependent nuclear receptor transcription coactivator activity  intracellular steroid hormone receptor signaling pathway  androgen receptor signaling pathway  exon-exon junction complex  positive regulation of circadian rhythm  vitamin D receptor binding  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  thyroid hormone receptor binding  positive regulation of mRNA splicing, via spliceosome  mRNA stabilization  phosphoprotein binding  extracellular exosome  
Ontology : EGO-EBIregulation of alternative mRNA splicing, via spliceosome  nuclear-transcribed mRNA catabolic process  core promoter sequence-specific DNA binding  RNA polymerase II transcription cofactor activity  transcription cofactor activity  transcription coactivator activity  RNA binding  receptor activity  protein binding  ATP binding  nucleus  nucleoplasm  transcription initiation from RNA polymerase II promoter  mRNA processing  circadian rhythm  RNA splicing  mediator complex  nuclear speck  ligand-dependent nuclear receptor transcription coactivator activity  intracellular steroid hormone receptor signaling pathway  androgen receptor signaling pathway  exon-exon junction complex  positive regulation of circadian rhythm  vitamin D receptor binding  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  thyroid hormone receptor binding  positive regulation of mRNA splicing, via spliceosome  mRNA stabilization  phosphoprotein binding  extracellular exosome  
REACTOMEQ9Y2W1 [protein]
REACTOME PathwaysR-HSA-381340 [pathway]   
NDEx NetworkTHRAP3
Atlas of Cancer Signalling NetworkTHRAP3
Wikipedia pathwaysTHRAP3
Orthology - Evolution
OrthoDB9967
GeneTree (enSembl)ENSG00000054118
Phylogenetic Trees/Animal Genes : TreeFamTHRAP3
HOVERGENQ9Y2W1
HOGENOMQ9Y2W1
Homologs : HomoloGeneTHRAP3
Homology/Alignments : Family Browser (UCSC)THRAP3
Gene fusions - Rearrangements
Fusion : MitelmanTHRAP3/AGO3 [1p34.3/1p34.3]  
Fusion : MitelmanTHRAP3/CAPZB [1p34.3/1p36.13]  [t(1;1)(p34;p36)]  
Fusion : MitelmanTHRAP3/MAP7D1 [1p34.3/1p34.3]  [t(1;1)(p34;p34)]  
Fusion : MitelmanTHRAP3/MUTYH [1p34.3/1p34.1]  [t(1;1)(p34;p34)]  
Fusion : MitelmanTHRAP3/SH3BP2 [1p34.3/4p16.3]  [t(1;4)(p34;p16)]  
Fusion : MitelmanTHRAP3/USP6 [1p34.3/17p13.2]  [t(1;17)(p34;p13)]  
Fusion : COSMICTHRAP3 [1p34.3]  -  USP6 [17p13.2]  [fusion_1410]  [fusion_1411]  
Fusion: TCGA_MDACCTHRAP3 1p34.3 CAPZB 1p36.13 LUAD
Fusion: TCGA_MDACCTHRAP3 1p34.3 EIF2C3 LUAD
Fusion: TCGA_MDACCTHRAP3 1p34.3 MAP7D1 1p34.3 BRCA
Fusion: TCGA_MDACCTHRAP3 1p34.3 MUTYH 1p34.1 BRCA
Tumor Fusion PortalTHRAP3
Fusion : TICdbTHRAP3 [1p34.3]  -  USP6 [17p13.2]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTHRAP3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)THRAP3
dbVarTHRAP3
ClinVarTHRAP3
1000_GenomesTHRAP3 
Exome Variant ServerTHRAP3
ExAC (Exome Aggregation Consortium)ENSG00000054118
GNOMAD BrowserENSG00000054118
Genetic variants : HAPMAP9967
Genomic Variants (DGV)THRAP3 [DGVbeta]
DECIPHERTHRAP3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTHRAP3 
Mutations
ICGC Data PortalTHRAP3 
TCGA Data PortalTHRAP3 
Broad Tumor PortalTHRAP3
OASIS PortalTHRAP3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTHRAP3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTHRAP3
intOGen PortalTHRAP3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch THRAP3
DgiDB (Drug Gene Interaction Database)THRAP3
DoCM (Curated mutations)THRAP3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)THRAP3 (select a term)
intoGenTHRAP3
NCG5 (London)THRAP3
Cancer3DTHRAP3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603809   
Orphanet
DisGeNETTHRAP3
MedgenTHRAP3
Genetic Testing Registry THRAP3
NextProtQ9Y2W1 [Medical]
TSGene9967
GENETestsTHRAP3
Target ValidationTHRAP3
Huge Navigator THRAP3 [HugePedia]
snp3D : Map Gene to Disease9967
BioCentury BCIQTHRAP3
ClinGenTHRAP3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9967
Chemical/Pharm GKB GenePA134893249
Clinical trialTHRAP3
Miscellaneous
canSAR (ICR)THRAP3 (select the gene name)
Probes
Litterature
PubMed89 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTHRAP3
EVEXTHRAP3
GoPubMedTHRAP3
iHOPTHRAP3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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