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FLASH GENE

Symbol

TRAF3IP2

contributors: mct/ - updated : 27-04-2011

HGNC name	TRAF3 interacting protein 2
HGNC id	1343

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001164283 4 splicing 907 NP_001157755 - 109 - 2000 10903453 NM_147686 9 splicing 2667 NP_679211 - 565 - 2000 10903453 also called C6orf4, isoform 2 NM_001164281 9 - 2664 NP_001157753 - 564 - 2000 10903453 NM_001164282 6 - 1137 NP_001157754 - 157 - 2000 10903453

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus       highly Respiratory respiratory tract larynx       Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna 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
	System Type Disorder Pubmed allergy asthm   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