E3 ubiquitin ligase TRAF3IP2

UniProt O43734 Organism Homo sapiens Gene C6orf2, C6orf4, C6orf5, C6orf6, TRAF3IP2 EC 2.3.2.27

Also known as: C6orf2, C6orf4, C6orf5, C6orf6, TRAF3IP2

Function

E3 ubiquitin ligase that catalyzes 'Lys-63'-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling. Transfers ubiquitin from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein. Essential adapter molecule in IL17A-mediated signaling. Upon IL17A stimulation, interacts with IL17RA and IL17RC receptor chains through SEFIR domains and catalyzes 'Lys-63'-linked polyubiquitination of TRAF6, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways.

Classification

Family (Pfam): PF08357 SEFIR
InterPro: E3_ubiq_ligase_TRAF3IP2, SEFIR_dom
Functional cluster: Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 1

9OT1 EM 3.00A

A predicted model is available from AlphaFold.

Gene Ontology · 41

Disease associations

psoriasis 13, susceptibility to MONDO:0013554
candidiasis, familial, 8 MONDO:0014230

Drugs targeting this protein · 1

IGURATIMOD inhibitor

Related proteins · sequence + function similarity

E3 ubiquitin ligase TRAF3IP2 0.97
Prospero homeobox protein 2 0.68
ETS translocation variant 4 0.67
ETS translocation variant 4 0.67
Prospero homeobox protein 2 0.66
T-box transcription factor TBX6 0.65
Junctional cadherin 5-associated protein 0.65
T-box transcription factor TBX6 0.64
Junctional cadherin 5-associated protein 0.64
Protein INCA1 0.64
Retinoic acid-induced protein 1 0.63
Storkhead-box protein 1 0.63

Co-cited proteins · studied together in the literature

E3 ubiquitin ligase TRAF3IP2 2 shared papers
TNF receptor-associated factor 6 2 shared papers
Interleukin-17 receptor A 2 shared papers
Interleukin-17A 2 shared papers
Interleukin-17 receptor B 1 shared papers
ORF8 protein 1 shared papers
Interleukin-17 receptor C 1 shared papers
Interleukin-17 receptor A 1 shared papers
Ubiquitin-conjugating enzyme E2 variant 1 1 shared papers
Ubiquitin-conjugating enzyme E2 N 1 shared papers

Literature · 13 cited papers

Title: ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway. IScience · 2021
An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity · 2013
Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat. Genet. · 2010
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat. Genet. · 2010
Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci. Signal. · 2009
The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
The DNA sequence and analysis of human chromosome 6. Nature · 2003
NF-kappaB activator Act1 associates with IL-1/Toll pathway adapter molecule TRAF6. FEBS Lett. · 2002
CIKS, a connection to Ikappa B kinase and stress-activated protein kinase. Proc. Natl. Acad. Sci. U.S.A. · 2000
Act1, an NF-kappa B-activating protein. Proc. Natl. Acad. Sci. U.S.A. · 2000
… and 1 more in the literature graph

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