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

    Gene ID: 10758, updated on 8-May-2013
    Official Symbol
    TRAF3IP2provided by HGNC
    Official Full Name
    TRAF3 interacting protein 2provided by HGNC
    Primary source
    HGNC:1343
    Locus tag
    RP3-487J7.3
    See related
    Ensembl:ENSG00000056972; HPRD:06129; MIM:607043; Vega:OTTHUMG00000015379
    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; 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]
    Location :
    6q21
    Sequence :
    Chromosome: 6; NC_000006.11 (111876581..111927477, complement)
    See TRAF3IP2 in Epigenomics, MapViewer

    Chromosome 6 - NC_000006.11Genomic Context describing neighboring genes Neighboring gene REV3-like, polymerase (DNA directed), zeta, catalytic subunit Neighboring gene bromodomain containing 7 pseudogene 4 Neighboring gene TRAF3IP2 antisense RNA 1 Neighboring gene uncharacterized LOC100996652 Neighboring gene FYN oncogene related to SRC, FGR, YES Neighboring gene uncharacterized LOC100506389

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. IL-17 receptor adaptor protein Act1/CIKS plays an evolutionarily conserved role in antiviral signaling. Ryzhakov G, et al. J Immunol, 2012 Nov 15. PMID 23066157.
    2. TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation. Qu F, et al. Mol Cell Biol, 2012 Oct. PMID 22851696.
    3. CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how a CIKS gene variant may predispose to psoriasis. Sønder SU, et al. J Immunol, 2012 Jun 15. PMID 22581863.
    4. Persistent stimulation with interleukin-17 desensitizes cells through SCFβ-TrCP-mediated degradation of Act1. Shi P, et al. Sci Signal, 2011 Nov 1. PMID 22045853.
    5. The expression of the receptor for advanced glycation end-products (RAGE) in RA-FLS is induced by IL-17 via Act-1. Heo YJ, et al. Arthritis Res Ther, 2011 Jul 12. PMID 21749686.

    See all (31) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. IL-17 receptor adaptor protein Act1/CIKS plays an evolutionarily conserved role in antiviral signaling.
      Title: IL-17 receptor adaptor protein Act1/CIKS plays an evolutionarily conserved role in antiviral signaling.
    2. The findings define a new role for the IKK-related kinases in suppressing IL-17-mediated NF-kappaB activation through TRAF6-dependent Act1 phosphorylation.
      Title: TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation.
    3. A CIKS mutant may promote the initiation of psoriatic inflammation
      Title: CIKS/Act1-mediated signaling by IL-17 cytokines in context: implications for how a CIKS gene variant may predispose to psoriasis.
    4. Act-1 contributed to the stimulatory effect of IL-17 on RAGE production in rheumatoid arthritis
      Title: The expression of the receptor for advanced glycation end-products (RAGE) in RA-FLS is induced by IL-17 via Act-1.
    5. Data indicate that knockdown of beta-TrCP1 and beta-TrCP2 markedly reduced IL-17-induced, phosphorylation-dependent ubiquitination and degradation of Act1.
      Title: Persistent stimulation with interleukin-17 desensitizes cells through SCFβ-TrCP-mediated degradation of Act1.
    6. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
    7. TRAF3IP2 represents a shared susceptibility for
      Title: Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2.
    8. Act1 transgene functions as an important regulator of B cell activating factor (BAFF)-mediated survival of transitional B cells and their maturation into follicular and marginal zone B cells.
      Title: The adaptor molecule Act1 regulates BAFF responsiveness and self-reactive B cell selection during transitional B cell maturation.
    9. Act1 mediates IL-17-induced signaling pathways through its E3 ubiquitin ligase activity and TRAF6 is a critical substrate of Act1, which indicates the importance of protein ubiquitination in the IL-17-dependent inflammatory response
      Title: Act1, a U-box E3 ubiquitin ligase for IL-17 signaling.
    10. Whereas Act1 interacts with the IL-17R through the C-terminal SEFIR domain, Act1 is recruited to CD40 and BAFFR indirectly, which is mediated by TRAF3 through the TRAF binding site in Act1[review]
      Title: Act1 modulates autoimmunity through its dual functions in CD40L/BAFF and IL-17 signaling.
    Submit: New GeneRIF Correction See all (14)

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    O43734 P25942 CD40    HPRD  PubMed  
    O43734 O15111 CHUK    HPRD  PubMed  
    O43734 O14920 IKBKB    HPRD  PubMed  
    O43734 Q9Y6K9 IKBKG    HPRD  PubMed  
    O43734 O43318 MAP3K7    HPRD  PubMed  
    O43734 Q99750 MDFI    HPRD  PubMed  
    O43734 Q13077 TRAF1    HPRD  PubMed  
    O43734 Q12933 TRAF2    HPRD  PubMed  
    O43734 Q13114 TRAF3    HPRD  PubMed  
    O43734 O43734 TRAF3IP2    HPRD  PubMed  
    O43734 O00463 TRAF5    HPRD  PubMed  
    O43734 Q9Y4K3 TRAF6    HPRD  PubMed  
    BioGRID:115979 BioGRID:107396 CD40    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:107569 CHUK    BioGRID  PubMed Affinity Capture-Western; Co-fractionation 
    BioGRID:115979 BioGRID:199230 Dlg4    BioGRID  PubMed Protein-peptide 
    BioGRID:115979 BioGRID:109767 IKBKB    BioGRID  PubMed Affinity Capture-Western; Co-fractionation 
    BioGRID:115979 BioGRID:115000 IKBKE    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    NP_003630.1 IKBKG    BIND  PubMed An unspecified isoform of CIKS interacts with IKK-gamma. This interaction was modeled on a demonstrated interaction between CIKS from an unspecified species and mouse IKK-gamma. 
    NP_003630.1 IKBKG    BIND  PubMed NEMO interacts with CIKS. This interaction was modeled on a demonstrated interaction between mouse NEMO and human CIKS. 
    BioGRID:115979 BioGRID:114089 IKBKG    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; Reconstituted Complex 
    BioGRID:115979 BioGRID:109818 IL17A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:117265 IL17RA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:200602 Ikbkg    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:115979 BioGRID:112748 MAP3K7    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:110353 MDFI    BioGRID  PubMed Two-hybrid 
    BioGRID:115979 BioGRID:118878 TBK1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:115979 BioGRID:125443 TNFRSF13C    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:113038 TRAF2    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:115979 BioGRID:113039 TRAF3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115979 BioGRID:115979 TRAF3IP2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:115979 BioGRID:113041 TRAF6    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid 
    BioGRID:115979 BioGRID:113164 UBC    BioGRID  PubMed Biochemical Activity 

    Markers

    Genotypes

    Homology

    Clone Names

    • MGC3581, DKFZp586G0522

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    B cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    humoral immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    immunoglobulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    intracellular signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    positive regulation of I-kappaB kinase/NF-kappaB cascade IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cellular_component ND
    No biological Data available
    more info
    		  
    Preferred Names
    adapter protein CIKS
    Names
    adapter protein CIKS
    NFkB-activating protein ACT1
    connection to IKK and SAPK/JNK
    nuclear factor NF-kappa-B activator 1

    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_032030.1 RefSeqGene

      Range
      5001..55897
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001164281.2 → NP_001157753.1  adapter protein CIKS 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, AW513823, DA130363, DA836923
      Consensus CDS
      CCDS55050.1
      UniProtKB/Swiss-Prot
      O43734
      UniProtKB/TrEMBL
      Q7Z6Q1
      Conserved Domains (1) summary
      pfam08357
      Location:401 – 538
      Blast Score: 353
      SEFIR; SEFIR domain

    2. NM_001164283.2 → NP_001157755.1  adapter protein CIKS isoform 5

      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, AW513823, BI856094, CB049654, DA130363
      Consensus CDS
      CCDS55049.1
      UniProtKB/Swiss-Prot
      O43734
      Conserved Domains (1) summary
      pfam08357
      Location:1 – 83
      Blast Score: 197
      SEFIR; SEFIR domain

    3. NM_147686.3 → NP_679211.2  adapter protein CIKS isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (2).
      Source sequence(s)
      AF136405, AF136406, AF136407, AL008730, AW296296, AW513823, DA130363, DA836923
      Consensus CDS
      CCDS5093.1
      UniProtKB/Swiss-Prot
      O43734
      Related
      ENSP00000357750, OTTHUMP00000017024, ENST00000368761, OTTHUMT00000041844
      Conserved Domains (1) summary
      pfam08357
      Location:401 – 539
      Blast Score: 364
      SEFIR; SEFIR domain

    RNA

    1. NR_028338.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript, and contains an additional exon at the 5' end compared to variant 1. It is represented as non-coding due to the presence of an upstream ORF (with a strong Kozak signal) that is predicted to interfere with the translation of the longest downstream ORF; translation of the upstream ORF renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AF136405, AF136407, AL008730, AW296296, AW513823, DA130363, DA836923

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000006.11 Reference GRCh37.p10 Primary Assembly

      Range
      111876581..111927477, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000138.1 Alternate HuRef

      Range
      109448986..109500061, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018917.1 Alternate CHM1_1.0

      Range
      111874471..111925374, 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. NM_147200.1: Suppressed sequence

      Description
      NM_147200.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01026085.1 (167067..215883) None
    genomic ABBA01026086.1 None
    genomic AL008730.1 (58072..85504) None
    genomic AMYH01016592.1 (262333..313236) None
    genomic CH471051.2 EAW48285.1
      EAW48286.1
      EAW48287.1
      EAW48288.1
    genomic CS135278.1 CAJ21527.1
    genomic Z97989.1 None
    mRNA AF085921.1 None
    mRNA AF136405.1 AAF67445.1
    mRNA AF136406.1 AAF67446.1
    mRNA AF136407.1 AAF67447.1
    mRNA AF272151.1 AAG15407.1
    mRNA AF274303.1 AAG15367.1
    mRNA AK025351.1 BAB15117.1
    mRNA AK026602.1 BAB15507.1
    mRNA AK310141.1 None
    mRNA AK310922.1 None
    mRNA AK314415.1 BAG37036.1
    mRNA AL050289.1 CAB43390.1
    mRNA AW296296.1 None
    mRNA AW513823.1 None
    mRNA BC002823.2 AAH02823.1
    mRNA BC026723.1 None
    mRNA BE904103.1 None
    mRNA BI856094.1 None
    mRNA BM449775.1 None
    mRNA CB049654.1 None
    mRNA DA130363.1 None
    mRNA DA836923.1 None
    mRNA DC348710.1 None
    mRNA DT217829.1 None
    other-genetic JF432241.1 ADZ15458.1
    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.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

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      • ClinVar
        Related medical variations
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
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        Link to related EST entry
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        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • GAP
        GAP Links
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        Related information in MedGen
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      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
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        Gene Genotype Report
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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