TRAF3IP2

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

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; OMA:TRAF3IP2 - orthologs
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 cartilage tissue oocyte skin of leg skin of abdomen body of uterus mucosa of transverse colon epithelium of colon islet of Langerhans ectocervix olfactory zone of nasal mucosa Top expressed in lacrimal gland parotid gland lip genital tubercle neural layer of retina seminal vesicula Paneth cell duodenum uterus large intestine 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
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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]