|Institutional Source||Beutler Lab|
|Gene Name||tripartite motif-containing 30A|
|Synonyms||Rpt-1, Rpt1, Trim30|
|Is this an essential gene?||Probably non essential (E-score: 0.081)|
|Stock #||R0049 (G1)|
|Chromosomal Location||104409025-104465193 bp(-) (GRCm38)|
|Type of Mutation||critical splice acceptor site|
|DNA Base Change (assembly)||C to T at 104429352 bp|
|Amino Acid Change|
|Ref Sequence||ENSEMBL: ENSMUSP00000076189 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000076922]|
|Predicted Effect||probably null
|Meta Mutation Damage Score||0.8681|
|Coding Region Coverage||
|Validation Efficiency||89% (108/122)|
|MGI Phenotype||PHENOTYPE: Homozygous null mice show increased CD4/CD8 ratio with age, an abnormal CD4+ T cell response upon TCR activation, and reduced effector function of CD4+ T cells. [provided by MGI curators]|
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Trim30a||
|Protein Function and Prediction|
Trim30a encodes Trim30 (alternatively, Rpt-1), a member of the tripartite-motif (TRIM) protein family (1). TRIM proteins function in the regulation of cell proliferation, differentiation, development, oncogenesis, apoptosis and antiviral responses (2). Trim30 is an intracellular protein that functions to downregulate gene expression directed by the promoter region of the gene encoding interleukin 2 receptor alpha chain and by the long terminal repeat of human immunodeficiency virus type 1 (3). Shi et al. have shown that TRIM30 is induced by TLR ligands (NF-κB-dependent) and interacts with the TAK1-TAB2-TAB3 complex (1). TRIM30 subsequently targets TAB2 and TAB3 for degradation and prevents TRAF6 autoubiquitination to negatively regulate TLR signaling (i.e., NF-κB activation) (1;4). TRIM30 is also involved in endotoxic tolerance (1). Trim30a overexpression in vivo increased survival in mice after LPS challenge (1). Hu et al. proposed that TRIM30 is involved in NLRP3 inflammasome activation (5). Knockdown of Trim30 increases ATP-induced caspase-1 activation and IL-1β production in bone marrow-derived macrophages as well as an increase in reactive oxygen species production triggered by LPS plus ATP (5). In addition, TRIM30 negatively regulates the IL-1β secretion evoked by many other NLRP3 inflammasome agonists (5). LTβR activation by activated CD4+ T cells induces TRIM30α expression and correlates with significantly lower levels of pro-inflammatory cytokine expression in vivo (4).
1. Shi, M., Deng, W., Bi, E., Mao, K., Ji, Y., Lin, G., Wu, X., Tao, Z., Li, Z., Cai, X., Sun, S., Xiang, C., and Sun, B. (2008) TRIM30 Alpha Negatively Regulates TLR-Mediated NF-Kappa B Activation by Targeting TAB2 and TAB3 for Degradation. Nat Immunol. 9, 369-377.
2. Nisole, S., Stoye, J. P., and Saib, A. (2005) TRIM Family Proteins: Retroviral Restriction and Antiviral Defence. Nat Rev Microbiol. 3, 799-808.
3. Patarca, R., Freeman, G. J., Schwartz, J., Singh, R. P., Kong, Q. T., Murphy, E., Anderson, Y., Sheng, F. Y., Singh, P., and Johnson, K. A. (1988) Rpt-1, an Intracellular Protein from helper/inducer T Cells that Regulates Gene Expression of Interleukin 2 Receptor and Human Immunodeficiency Virus Type 1. Proc Natl Acad Sci U S A. 85, 2733-2737.
4. Wimmer, N., Huber, B., Wege, A. K., Barabas, N., Rohrl, J., Pfeffer, K., and Hehlgans, T. (2012) Lymphotoxin-Beta Receptor Activation on Macrophages Ameliorates Acute DSS-Induced Intestinal Inflammation in a TRIM30alpha-Dependent Manner. Mol Immunol. 51, 128-135.
|Science Writer||Anne Murray|