Incidental Mutation 'P0016:Traip'
ID7596
Institutional Source Beutler Lab
Gene Symbol Traip
Ensembl Gene ENSMUSG00000032586
Gene NameTRAF-interacting protein
SynonymsTrip
MMRRC Submission 038269-MU
Accession Numbers

NCBI RefSeq: NM_011634.3; MGI:1096377

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #P0016 (G1)
Quality Score
Status Validated
Chromosome9
Chromosomal Location107950136-107972270 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 107968656 bp
ZygosityHeterozygous
Amino Acid Change Aspartic acid to Glycine at position 316 (D316G)
Ref Sequence ENSEMBL: ENSMUSP00000040001 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000049348]
Predicted Effect possibly damaging
Transcript: ENSMUST00000049348
AA Change: D316G

PolyPhen 2 Score 0.928 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000040001
Gene: ENSMUSG00000032586
AA Change: D316G

DomainStartEndE-ValueType
RING 7 49 6.68e-6 SMART
coiled coil region 70 278 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000194191
Predicted Effect noncoding transcript
Transcript: ENSMUST00000194538
Predicted Effect noncoding transcript
Transcript: ENSMUST00000195803
Meta Mutation Damage Score 0.0725 question?
Coding Region Coverage
  • 1x: 85.6%
  • 3x: 81.0%
  • 10x: 66.8%
  • 20x: 50.1%
Validation Efficiency 96% (97/101)
MGI Phenotype Strain: 3764469
Lethality: E7-E9
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit embryonic lethality at prior to E8.5, embryonic growth retardation, decreased embryonic size, decreased cell proliferation and increased apoptosis. [provided by MGI curators]
Allele List at MGI

All alleles(10) : Targeted(1) Gene trapped(9)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700123K08Rik A T 5: 138,562,938 L154* probably null Het
4930432E11Rik T C 7: 29,563,112 noncoding transcript Het
Arap3 T A 18: 37,984,348 T892S probably benign Het
Ctnnd2 G A 15: 30,966,938 V987I probably benign Het
Dennd6b T C 15: 89,186,977 I351V probably benign Het
Kif27 G A 13: 58,303,452 Q1021* probably null Het
Klb G A 5: 65,379,923 W865* probably null Het
Mbd1 C T 18: 74,274,538 R130* probably null Het
Mroh7 T A 4: 106,707,857 probably null Het
Myo16 C T 8: 10,400,596 probably benign Het
Rbm22 T A 18: 60,570,770 probably benign Het
Rnaseh2a C G 8: 84,959,800 D206H probably damaging Het
Slain1 A G 14: 103,685,674 T187A probably benign Het
Slamf6 A G 1: 171,936,501 T154A probably damaging Het
Ttn T C 2: 76,811,183 D5196G probably damaging Het
Ubr5 C T 15: 38,000,578 V1569M probably damaging Het
Zfp750 T A 11: 121,513,978 K24* probably null Het
Zfp799 T C 17: 32,819,357 E645G possibly damaging Het
Other mutations in Traip
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00088:Traip APN 9 107970550 missense probably benign 0.15
IGL01457:Traip APN 9 107970472 missense probably benign 0.00
IGL01597:Traip APN 9 107955924 critical splice donor site probably null
IGL02197:Traip APN 9 107968737 missense possibly damaging 0.89
IGL03077:Traip APN 9 107962926 unclassified probably benign
IGL03226:Traip APN 9 107970993 missense probably damaging 0.97
BB008:Traip UTSW 9 107971042 missense probably benign 0.04
BB018:Traip UTSW 9 107971042 missense probably benign 0.04
R1693:Traip UTSW 9 107970030 missense probably damaging 0.99
R2054:Traip UTSW 9 107962919 missense probably benign 0.08
R4396:Traip UTSW 9 107959487 missense probably benign 0.02
R4617:Traip UTSW 9 107970019 missense probably benign 0.00
R6151:Traip UTSW 9 107970619 critical splice donor site probably null
R6241:Traip UTSW 9 107968734 missense probably benign 0.33
R6920:Traip UTSW 9 107961041 nonsense probably null
R7177:Traip UTSW 9 107960985 missense possibly damaging 0.62
R7191:Traip UTSW 9 107970017 missense probably benign
R7504:Traip UTSW 9 107961544 missense probably benign 0.05
R7931:Traip UTSW 9 107971042 missense probably benign 0.04
R7939:Traip UTSW 9 107955878 missense probably benign 0.21
R8228:Traip UTSW 9 107961066 missense probably benign 0.16
X0018:Traip UTSW 9 107961656 critical splice donor site probably null
Protein Function and Prediction

TRAIP (alternatively, TRIP) is a RING-type E3 ubiquitin ligase that interacts with TRAF and functions to repress NF-κB signaling to regulate proliferation and differentiation [(1); reviewed in (2)].  Also, TRAIP interacts with Syk, a non-receptor protein kinase that acts as a tumor suppressor (3).  This interaction reduces the Syk-mediated increase in TNFα-dependent activation of NF-κB (4). TRAIP also interacts with the tumor suppressor CYLD (5).

Expression/Localization

Northern blot analysis of mouse tissues identified the Traip transcript in testis, thymus, and spleen (6). In keratinocytes undergoing differentiation (7) as well as in an immortalized monocytic cell line (1), Traip is downregulated.

Background

siRNA-mediated knockdown of TRIP resulted in decreased keteratinocyte proliferation and cell cycle arrest at the G1/S phase (7).

 

Traiptm1Jarh/tm1Jarh; MGI:3764469

C57BL/6J

Homozygous mice are embryonic lethal by E8.5 (8).  Embryos examined at earlier time-points are decreased in size, have loss of embryonic tissues, absent proamniotic cavity, increased apoptosis, and decreased cell proliferation (8).

References
Posted On2012-10-05
Science WriterAnne Murray