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FLASH GENE
Symbol TRAF3IP2 contributors: mct/ - updated : 27-04-2011
HGNC name TRAF3 interacting protein 2
HGNC id 1343
Location 6q21      Physical location : 111.880.144 - 111.927.474
Synonym name
  • connection to IKK and SAPK/JNK
  • nuclear factor NF-kappa-B activator 1
  • chromosome 6 open reading frame 5
  • chromosome 6 open reading frame 4
  • chromosome 6 open reading frame 2
  • adapter protein CIKS
  • NFkB-activating protein ACT1
  • Synonym symbol(s) ACT1, CIKS, C6orf5, C6orf6, MGC3581, C6orf4, C6orf2, DKFZP586G0522
    DNA
    TYPE functioning gene
    SPECIAL FEATURE overlapping, gene in gene, opposite orientation, antisens
    text
  • C6UAS, overlaps exon 2 and is transcribed in the antisense orientation from the complementary strand of C6orf4
  • isoform encoded by a complex transcription unit
  • STRUCTURE 47.33 kb     9 Exon(s)
    regulatory sequence Promoter (CAAT box)
    cytosine-phosphate-guanine/HTF
    text structure
  • 10 exons, taken in a unit of 13 exons including exon 2
  • an initiator (Inr), 'GC' and 'CAAT' boxes
  • MAPPING cloned Y linked N status provisional
    regionally located in a region involved in replicative senescence and schizophrenia
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 907 - 109 - 2000 10903453
    9 splicing 2667 - 565 - 2000 10903453
    also called C6orf4, isoform 2
    9 - 2664 - 564 - 2000 10903453
    6 - 1137 - 157 - 2000 10903453
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Respiratoryrespiratory tractlarynx   
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a domain in the N terminus (likely situated between AAs 10 and 21) that is required for interaction with TRAF6 and activation of NFKB
  • a coiled coil domain
  • a series of alpha helices at the C terminus
  • leucine zipper domain
  • HOMOLOGY
    interspecies ortholog to murine Traf3ip2
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • involved in regulating response to cytokines by members of the REL/NFKB transcription factor family in response to pathogens
  • recruited to CD40 and TNFRSF13B indirectly, which is mediated by TRAF3 through the TRAF binding site in TRAF3IP2 (
  • modulates the survival of autoreactive B cells mainly through its negative regulatory role in TNFSF13B-mediated cell survival
  • essential adaptor molecule in IL17-mediated signaling and is recruited to the IL17 receptor (IL17R) upon IL17 stimulation through an interaction between its SEFIR domain and that of the IL17R
  • mediates IL17-induced signaling pathways through its E3 ubiquitin ligase activity
  • essential role of epithelial-derived TRAF3IP2 in allergic pulmonary inflammation through the distinct impact of the IL17R-TRAF3IP2 and IL25R-TRAF3IP2 axes (
  • plays a critical role in the regulation of transitional B cell survival and maturation
  • negative regulator of TNFSF13B-mediated signaling
  • regulates TNFSF13B responsiveness and self-reactive B cell selection during transitional B cell maturation
  • involved in IL17 signaling and which interacts with members of the REL/NF-KB transcription factor family (
  • negatively regulates B-cell survival through its interaction with TRAF3
  • signaling adaptor involved in the regulation of adaptive immunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text intracellular signaling cascade
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TRAF protein
  • interaction with the regulatory subunit NEMO/IKKgamma of IKK complex, and the stress-activated protein kinase (SAPK)/JNK
  • TRAF6 is a critical substrate of TRAF3IP2, which indicates the importance of protein ubiquitination in the IL17-dependent inflammatory response
  • TRAF6 is essential for IL17A/TRAF3IP2-mediated activation of NFKB
  • cell & other
    REGULATION
    activated by cytokines
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to psoriasis vulgaris and psoriatic arthritis
    Variant & Polymorphism SNP
  • rs33980500 highly associated with psoriasis vulgaris and psoriatic arthritis
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    allergyasthm 
    potential therapeutic targetin atopic diseases, including allergic asthma
    ANIMAL & CELL MODELS
  • deficiency of Act1 in mice results in peripheral B cell hyperplasia and development of autoimmunity
  • mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjögren's syndrome (SS), in association with systemic lupus erythematosus-like nephritis