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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
    mouse all
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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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    NEW Try the new Transcript table

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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