TRAF3IP2

TRAF3IP2
Identifiers
Aliases	TRAF3IP2 , ACT1, C6orf2, C6orf4, C6orf5, C6orf6, CANDF8, CIKS, PSORS13, TRAF3 interacting protein 2
External IDs	OMIM: 607043 MGI: 2143599 HomoloGene: 15885 GeneCards: TRAF3IP2
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q21 Start 111,555,381 bp [1] End 111,606,906 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 B1 Start 39,488,930 bp [2] End 39,531,303 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte skin of abdomen islet of Langerhans right uterine tube canal of the cervix secondary oocyte body of stomach smooth muscle tissue minor salivary gland rectum Top expressed in lacrimal gland parotid gland lip seminal vesicula Paneth cell duodenum uterus large intestine colon spermatocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding protein binding Cellular component intracellular anatomical structure cellular component Biological process positive regulation of I-kappaB kinase/NF-kappaB signaling intracellular signal transduction humoral immune response B cell apoptotic process positive regulation of defense response to virus by host Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10758 103213 Ensembl ENSG00000056972 ENSMUSG00000019842 UniProt O43734 Q8N7N6 RefSeq (mRNA) NM_001164281 NM_001164282 NM_001164283 NM_147200 NM_147686 NM_134000 RefSeq (protein) NP_001157753 NP_001157755 NP_671733 NP_679211 NP_598761 Location (UCSC) Chr 6: 111.56 – 111.61 Mb Chr 10: 39.49 – 39.53 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Adapter protein CIKS is a protein that in humans is encoded by the TRAF3IP2 gene. ^{[5] [6] [7]}

This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Two alternative transcripts encoding different proteins have been identified. A third transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. ^[7]

Cellular function

TRAF3IP2 is the key activator of Th17-mediated inflammatory responses but also suppresses the humoral B cell response by negatively regulating CD40L and BAFF signaling. ^[8] TRAF3IP2 seems to be more specific to Brucella infections than other Gram-negative bacteria. In the study of Degos et al., TRAF3IP2 expression was increased fourfold in human blood DCs after exposure to the Brucella virulence factor CβG (β-1,2 cyclic glucan) compared to the E. coli lipopolysaccharides (LPS) ^[9] CβG is a highly abundant virulence factor of Brucella that modulates membrane rafts of the infected cell necessary for the intracellular escape (Arellano-Reynoso et al., 2005). It is thus one of the most Brucella-specific toxins recognized by immune cells. ^{[9] [10]} LPS is another important Gram-negative virulence factor. However, it is altered in Brucella, so it is only weakly immunostimulatory. ^{[11] [12]} Also, TRAF3IP2 and Th2-LCR lncRNA expression was particularly increased in the acute phase of brucellosis. During relapse phase of brucellosis, TRAF3IP2 expression seemed to decrease, whereas the Th2-LCR lncRNA level remained high. ^[13]

Interactions

TRAF3IP2 has been shown to interact with IKBKG. ^{[5] [6]}

References

1. GRCh38: Ensembl release 89: ENSG00000056972 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019842 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U (September 2000). "CIKS, a connection to Ikappa B kinase and stress-activated protein kinase". Proceedings of the National Academy of Sciences of the United States of America. 97 (19): 10494–10499. Bibcode:2000PNAS...9710494L. doi: 10.1073/pnas.190245697 . PMC   27052 . PMID   10962033.
6. Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, et al. (September 2000). "Act1, an NF-kappa B-activating protein". Proceedings of the National Academy of Sciences of the United States of America. 97 (19): 10489–10493. Bibcode:2000PNAS...9710489L. doi: 10.1073/pnas.160265197 . PMC   27051 . PMID   10962024.
7. "Entrez Gene: TRAF3IP2 TRAF3 interacting protein 2".
8. Qian Y, Qin J, Cui G, Naramura M, Snow EC, Ware CF, et al. (October 2004). "Act1, a negative regulator in CD40- and BAFF-mediated B cell survival". Immunity. 21 (4): 575–587. doi: 10.1016/j.immuni.2004.09.001 . PMID   15485634.
9. Degos C, Gagnaire A, Banchereau R, Moriyón I, Gorvel JP (2015). "Brucella CβG induces a dual pro- and anti-inflammatory response leading to a transient neutrophil recruitment". Virulence. 6 (1): 19–28. doi:10.4161/21505594.2014.979692. PMC   4603436 . PMID   25654761.
10. Arellano-Reynoso B, Lapaque N, Salcedo S, Briones G, Ciocchini AE, Ugalde R, et al. (June 2005). "Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival". Nature Immunology. 6 (6): 618–625. doi:10.1038/ni1202. PMID   15880113. S2CID   32005324.
11. Lapaque N, Moriyon I, Moreno E, Gorvel JP (February 2005). "Brucella lipopolysaccharide acts as a virulence factor". Current Opinion in Microbiology. 8 (1): 60–66. doi:10.1016/j.mib.2004.12.003. PMID   15694858.
12. Barquero-Calvo E, Chaves-Olarte E, Weiss DS, Guzmán-Verri C, Chacón-Díaz C, Rucavado A, et al. (July 2007). "Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection". PLOS ONE. 2 (7): e631. Bibcode:2007PLoSO...2..631B. doi: 10.1371/journal.pone.0000631 . PMC   1910614 . PMID   17637846.
13. Gheitasi R, Keramat F, Khosravi S, Hajilooi M, Pletz MW, Makarewicz O (2021). "Evaluation of Th2 and Th17 Immunity-Related Factors as Indicators of Brucellosis". Frontiers in Cellular and Infection Microbiology. 11: 786994. doi: 10.3389/fcimb.2021.786994 . PMC   8777051 . PMID   35071039.  This article incorporates text by Reza Gheitasi available under the CC BY 1.0 license.

Further reading

• Morelli C, Magnanini C, Mungall AJ, Negrini M, Barbanti-Brodano G (July 2000). "Cloning and characterization of two overlapping genes in a subregion at 6q21 involved in replicative senescence and schizophrenia". Gene. 252 (1–2): 217–225. doi:10.1016/S0378-1119(00)00231-6. PMID   10903453.
• Qian Y, Zhao Z, Jiang Z, Li X (July 2002). "Role of NF kappa B activator Act1 in CD40-mediated signaling in epithelial cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (14): 9386–9391. Bibcode:2002PNAS...99.9386Q. doi: 10.1073/pnas.142294499 . PMC   123150 . PMID   12089335.
• Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U (October 2002). "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases". The Journal of Biological Chemistry. 277 (40): 37029–37036. doi: 10.1074/jbc.M205069200 . PMID   12133833.
• Xia YF, Li YD, Li X, Geng JG (August 2002). "Identification of alternatively spliced Act1 and implications for its roles in oncogenesis". Biochemical and Biophysical Research Communications. 296 (2): 406–412. doi:10.1016/S0006-291X(02)00887-2. PMID   12163033.
• Kanamori M, Kai C, Hayashizaki Y, Suzuki H (December 2002). "NF-kappaB activator Act1 associates with IL-1/Toll pathway adaptor molecule TRAF6". FEBS Letters. 532 (1–2): 241–246. doi:10.1016/S0014-5793(02)03688-8. PMID   12459498. S2CID   83623149.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, et al. (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–3318. doi:10.1038/sj.onc.1206406. PMID   12761501.
• Mauro C, Vito P, Mellone S, Pacifico F, Chariot A, Formisano S, Leonardi A (September 2003). "Role of the adaptor protein CIKS in the activation of the IKK complex". Biochemical and Biophysical Research Communications. 309 (1): 84–90. doi:10.1016/S0006-291X(03)01532-8. hdl: 2268/1240 . PMID   12943667.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.