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TRAF3IP2 TRAF3 interacting protein 2 [ Homo sapiens (human) ]

Gene ID: 10758, updated on 2-Nov-2024

Summary

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Official Symbol
TRAF3IP2provided by HGNC
Official Full Name
TRAF3 interacting protein 2provided by HGNC
Primary source
HGNC:HGNC:1343
See related
Ensembl:ENSG00000056972 MIM:607043; AllianceGenome:HGNC:1343
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ACT1; CIKS; C6orf2; C6orf4; C6orf5; C6orf6; CANDF8; PSORS13
Summary
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. Several alternative transcripts encoding different isoforms have been identified. Another 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. [provided by RefSeq, Aug 2009]
Expression
Ubiquitous expression in endometrium (RPKM 6.1), stomach (RPKM 4.8) and 25 other tissues See more
Orthologs
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Genomic context

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See TRAF3IP2 in Genome Data Viewer
Location:
6q21
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (111555381..111605878, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (112738381..112788887, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (111876584..111927081, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene TRAF3IP2 antisense RNA 1 Neighboring gene uncharacterized LOC107986520 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111828147-111828670 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111828671-111829193 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_87727 Neighboring gene uncharacterized LOC107986522 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:111861530-111861704 Neighboring gene VISTA enhancer hs1690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:111880567-111881066 Neighboring gene MPRA-validated peak6037 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111885602-111886274 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:111886439-111887638 Neighboring gene TRAF3IP2 eExon liver enhancer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24949 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24950 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:111928045-111928677 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111941387-111941922 Neighboring gene MPRA-validated peak6038 silencer Neighboring gene uncharacterized LOC105377944 Neighboring gene Sharpr-MPRA regulatory region 7524 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111982565-111983248 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111983249-111983930 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:111983931-111984612 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:111998453-111999376 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:112003973-112004474 Neighboring gene uncharacterized LOC105377945 Neighboring gene FYN proto-oncogene, Src family tyrosine kinase

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A Novel Nuclear Function for the Interleukin-17 Signaling Adaptor Protein Act1. Velichko S, et al. PLoS One, 2016. PMID 27723765, Free PMC Article
  2. The Act1 D10N missense variant impairs CD40 signaling in human B-cells. Yu N, et al. Genes Immun, 2019 Jan. PMID 29302052, Free PMC Article
  3. Neutrophil Extracellular Traps Induce Human Th17 Cells: Effect of Psoriasis-Associated TRAF3IP2 Genotype. Lambert S, et al. J Invest Dermatol, 2019 Jun. PMID 30528823, Free PMC Article
  4. Identification of alternatively spliced Act1 and implications for its roles in oncogenesis. Xia YF, et al. Biochem Biophys Res Commun, 2002 Aug 16. PMID 12163033
  5. Genetic polymorphism in the TRAF3IP2 gene is associated with psoriasis vulgaris in a Japanese population. Hayashi M, et al. J Dermatol Sci, 2014 Mar. PMID 24373565

See all (90) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NF-kappaB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer.
    Title: NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer.
  2. alphaCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform.
    Title: αCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform.
  3. TRAF3IP2 regulated by FOXO4 affects fibroblast proliferation, migration, and extracellular matrix deposition in keloid through the TGF-beta1/Smad pathway.
    Title: TRAF3IP2 regulated by FOXO4 affects fibroblast proliferation, migration, and extracellular matrix deposition in keloid through the TGF-β1/Smad pathway.
  4. A multilocus genetic study evidences the association of autoimmune-related genes with Psoriatic Arthritis in Italian patients.
    Title: A multilocus genetic study evidences the association of autoimmune-related genes with Psoriatic Arthritis in Italian patients.
  5. A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis.
    Title: A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis.
  6. Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency.
    Title: Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency.
  7. Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.
    Title: Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.
  8. A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.
    Title: A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.
  9. Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
    Title: Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
  10. Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration.
    Title: Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration.
Submit: New GeneRIF Correction See all GeneRIFs (52)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Candidiasis, familial, 8
MedGen: C3714992 OMIM: 615527 GeneReviews: Not available
Compare labs
Psoriasis 13, susceptibility to
MedGen: C3279754 OMIM: 614070 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
EBI GWAS Catalog
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.
EBI GWAS Catalog
Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC3581, DKFZp586G0522

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor binding IEA
Inferred from Electronic Annotation
more info
  
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in B cell affinity maturation IEA
Inferred from Electronic Annotation
more info
  
involved_in B cell apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in B cell homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in CD40 signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in T cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in T-helper 17 type immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in eosinophil homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in eosinophil mediated immunity IEA
Inferred from Electronic Annotation
more info
  
involved_in establishment of T cell polarity IEA
Inferred from Electronic Annotation
more info
  
involved_in heart development IEA
Inferred from Electronic Annotation
more info
  
involved_in humoral immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in interleukin-17-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in interleukin-17A-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in intracellular signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in kidney development IEA
Inferred from Electronic Annotation
more info
  
involved_in leukocyte activation involved in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in lymph node development IEA
Inferred from Electronic Annotation
more info
  
involved_in mRNA stabilization IEA
Inferred from Electronic Annotation
more info
  
involved_in mucus secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in neutrophil activation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of canonical NF-kappaB signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of canonical NF-kappaB signal transduction IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in positive regulation of defense response to virus by host IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K63-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein import into nucleus IEA
Inferred from Electronic Annotation
more info
  
involved_in protein localization to P-body IEA
Inferred from Electronic Annotation
more info
  
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction involved in regulation of gene expression IEA
Inferred from Electronic Annotation
more info
  
involved_in skin development IEA
Inferred from Electronic Annotation
more info
  
involved_in spleen development IEA
Inferred from Electronic Annotation
more info
  
involved_in transitional two stage B cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in tumor necrosis factor-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in type 2 immune response IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cellular_component ND
No biological Data available
more info
  
is_active_in cytoplasm IC
Inferred by Curator
more info
 PubMed 
located_in cytoplasmic vesicle IEA
Inferred from Electronic Annotation
more info
  
is_active_in extrinsic component of cytoplasmic side of plasma membrane IC
Inferred by Curator
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
E3 ubiquitin ligase TRAF3IP2
Names
E3 ubiquitin-protein ligase CIKS
NFkB-activating protein ACT1
adapter protein CIKS
connection to IKK and SAPK/JNK
nuclear factor NF-kappa-B activator 1
symbol withdrawn, see C6orf4
NP_001157753.1
NP_001157755.1
NP_671733.2
NP_679211.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032030.2 RefSeqGene

    Range
    5001..55498
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1337

mRNA and Protein(s)

  1. NM_001164281.3 → NP_001157753.1  E3 ubiquitin ligase TRAF3IP2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate in-frame acceptor splice site at an internal coding exon compared to variant 2. This results in an isoform (3) that is 1 aa shorter than isoform 2.
    Source sequence(s)
    AF136405, AF136407, AK025351, AL008730, AW296296, DA130363, DA836923
    Consensus CDS
    CCDS55050.1
    UniProtKB/TrEMBL
    A0A8V8TQD6
    Related
    ENSP00000352889.4, ENST00000359831.8
    Conserved Domains (2) summary
    pfam08357
    Location:401 → 542
    SEFIR; SEFIR domain
    cl01053
    Location:311 → 409
    SGNH_hydrolase; SGNH_hydrolase, or GDSL_hydrolase, is a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely ...

  2. NM_001164283.3 → NP_001157755.1  E3 ubiquitin ligase TRAF3IP2 isoform 5

    See identical proteins and their annotated locations for NP_001157755.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks several exons from the 5' end, and contains an alternate 5' terminal exon compared to variant 2. This results in translation initiation from a downstream AUG, and a shorter isoform (5) compared to isoform 2.
    Source sequence(s)
    AF136405, AF136407, AL008730, AW296296, CB049654, DA130363
    Consensus CDS
    CCDS55049.1
    UniProtKB/Swiss-Prot
    O43734
    Related
    ENSP00000357724.1, ENST00000368735.1
    Conserved Domains (1) summary
    cl23749
    Location:1 → 87
    TIR_2; TIR domain

  3. NM_147200.3 → NP_671733.2  E3 ubiquitin ligase TRAF3IP2 isoform 1

    See identical proteins and their annotated locations for NP_671733.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) contains an alternate 5' exon which results in the use of an upstream in-frame start codon, compared to variant 2. The encoded isoform (1) has a longer N-terminus compared to isoform 2.
    Source sequence(s)
    AF136405, AK025351, AL008730, DA665549
    Consensus CDS
    CCDS5092.1
    UniProtKB/Swiss-Prot
    B2RAY9, E1P555, O43734, Q5R3A3, Q7Z6Q1, Q7Z6Q2, Q7Z6Q3, Q9H5W2, Q9H6Y3, Q9NS14, Q9UG72
    UniProtKB/TrEMBL
    A0A8V8TQD6
    Related
    ENSP00000345984.6, ENST00000340026.10
    Conserved Domains (2) summary
    pfam08357
    Location:410 → 552
    SEFIR; SEFIR domain
    cl01053
    Location:320 → 418
    SGNH_hydrolase; SGNH_hydrolase, or GDSL_hydrolase, is a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely ...

  4. NM_147686.4 → NP_679211.2  E3 ubiquitin ligase TRAF3IP2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes isoform (2).
    Source sequence(s)
    AF136405, AF136406, AF136407, AL008730, AW296296, DA130363
    Consensus CDS
    CCDS5093.1
    UniProtKB/TrEMBL
    A0A8V8TQD6
    Related
    ENSP00000357750.5, ENST00000368761.11
    Conserved Domains (2) summary
    pfam08357
    Location:401 → 543
    SEFIR; SEFIR domain
    cl01053
    Location:311 → 409
    SGNH_hydrolase; SGNH_hydrolase, or GDSL_hydrolase, is a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    111555381..111605878 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    112738381..112788887 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001164282.1: Suppressed sequence

    Description
    NM_001164282.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  2. NR_028338.2: Suppressed sequence

    Description
    NR_028338.2: This RefSeq was permanently suppressed because it is now thought that this transcript variant encodes a protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43734.3 GenPept UniProtKB/Swiss-Prot:O43734

Gene LinkOut

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