TGFBRAP1 (transforming growth factor, beta receptor associated protein 1)

2011-04-01   Jens U Wurthner 

Translational Pharmacology, Discovery Medicine, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, USA

Identity

HGNC
LOCATION
2q12.1
LOCUSID
ALIAS
TRAP-1,TRAP1,VPS3
FUSION GENES

DNA/RNA

Atlas Image
Generated by BlastAnalyser in 2005 (unpublished). Contig: NT_022171.13 (gi: 29789878).

Description

Encoded on the minus strand. 12 exons, exon number 1 is not depicted in the diagram and appears to undergo differential splicing, according to recent NCBI-AceView (accessed 17 Apr 2011).

Transcription

Work by the Wurthner lab in 2003-2005 identified an 860 aa protein that could be matched with genomic sequences. Recently predicted proteins from mRNA variants describe translation products of 896, 952, 161 and 30 aminino acids (NCBI AceView, accessed 17 April 2011).

Proteins

Atlas Image
CNH: Citron Homology Domain; CLH: Clathrin Homology Domain; VPS39: Vesicle Protein Sorting Protein 39 Domain.

Description

A fragment of TGFBRAP1 was initially identified in a Yeast-2-Hybrid screen as a TGF-beta type I receptor interacting protein (Charng et al., 2002). Further work by Wurthner et al. demonstrated binding of the full-length molecule exclusively to either TGF-beta receptor I and TGF-beta receptor II, or to Smad4, suggesting TGFBRAP1 to be a Smad4 chaperone (Wurthner et al., 2001). Furthermore, receptor activated Smads were shown to compete for binding of TRAP1 with Smad4, suggesting only a transient association between TRAP1 and Smad4. In addition, an interaction of TRAP1 with 5-lipoxgenase in a yeast two-hybrid system was described by a different group (Provost et al., 1999). Gene inactivation of TGFBRAP1 through conventional targeting leads to early developmental arrest of murine embryos around day E 6.5 (Messler et al., 2010).

Expression

Ubiquitous.

Localisation

Punctate pattern suggestive of endosomal localisation.

Function

Chaperone for Smad4 in the TGF-beta signal transduction cascade (Wurthner et al., 2001).
Endosomal trafficking (circumstantial evidence: domain structure and early embryonic lethality; Messler et al., 2010).

Homology

hVPS39 (hVam6, hTrap-like-Protein).

Implicated in

Bibliography

Pubmed IDLast YearTitleAuthors
95452581998A novel protein distinguishes between quiescent and activated forms of the type I transforming growth factor beta receptor.Charng MJ et al
129416982003TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling.Felici A et al
209616512011The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development.Messler S et al
100515631999Interaction of 5-lipoxygenase with cellular proteins.Provost P et al
112783022001Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone.Wurthner JU et al

Other Information

Locus ID:

NCBI: 9392
MIM: 606237
HGNC: 16836
Ensembl: ENSG00000135966

Variants:

dbSNP: 9392
ClinVar: 9392
TCGA: ENSG00000135966
COSMIC: TGFBRAP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000135966ENST00000258449Q8WUH2
ENSG00000135966ENST00000393359Q8WUH2
ENSG00000135966ENST00000595531Q8WUH2

Expression (GTEx)

0
5
10
15
20
25
30

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
197543112009Genomewide association study of a rapid progression cohort identifies new susceptibility alleles for AIDS (ANRS Genomewide Association Study 03).53
219984502011Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity.36
168868952006Genetic predisposition of responsiveness to therapy for chronic hepatitis C.12
273019512016Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer.9
294760492018Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions.5
304612002019The variant at TGFBRAP1 is significantly associated with type 2 diabetes mellitus and affects diabetes-related miRNA expression.2
258560022015Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and plasma TGF-β1.0

Citation

Jens U Wurthner

TGFBRAP1 (transforming growth factor, beta receptor associated protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2011-04-01

Online version: http://atlasgeneticsoncology.org/gene/42542/tgfbrap1