O43734 · CIKS_HUMAN

  • Protein
    E3 ubiquitin ligase TRAF3IP2
  • Gene
    TRAF3IP2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

E3 ubiquitin ligase that catalyzes 'Lys-63'-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling (PubMed:19825828).
Transfers ubiquitin from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein (PubMed:19825828).
Essential adapter molecule in IL17A-mediated signaling (PubMed:19825828, PubMed:24120361).
Upon IL17A stimulation, interacts with IL17RA and IL17RC receptor chains through SEFIR domains and catalyzes 'Lys-63'-linked polyubiquitination of TRAF6, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways (PubMed:19825828).

Caution

The presence of U-box domain is not predicted by SMART and SWISS-MODEL tools.

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytoplasmic vesicle
Cellular Componentextrinsic component of cytoplasmic side of plasma membrane
Cellular Componentnucleus
Molecular Functionsignaling receptor binding
Molecular Functionubiquitin protein ligase activity
Biological ProcessB cell affinity maturation
Biological ProcessB cell apoptotic process
Biological ProcessB cell homeostasis
Biological ProcessCD40 signaling pathway
Biological Processeosinophil homeostasis
Biological Processeosinophil mediated immunity
Biological Processestablishment of T cell polarity
Biological Processheart development
Biological Processhumoral immune response
Biological Processinflammatory response
Biological Processinterleukin-17-mediated signaling pathway
Biological Processinterleukin-17A-mediated signaling pathway
Biological Processintracellular signal transduction
Biological Processkidney development
Biological Processleukocyte activation involved in inflammatory response
Biological Processlymph node development
Biological ProcessmRNA stabilization
Biological Processmucus secretion
Biological Processneutrophil activation
Biological Processpositive regulation of canonical NF-kappaB signal transduction
Biological Processpositive regulation of defense response to virus by host
Biological Processprotein import into nucleus
Biological Processprotein K63-linked ubiquitination
Biological Processprotein localization to P-body
Biological Processresponse to xenobiotic stimulus
Biological Processsignal transduction involved in regulation of gene expression
Biological Processskin development
Biological Processspleen development
Biological ProcessT cell differentiation
Biological ProcessT-helper 17 type immune response
Biological Processtransitional two stage B cell differentiation
Biological Processtumor necrosis factor-mediated signaling pathway
Biological Processtype 2 immune response

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin ligase TRAF3IP2
  • EC number
  • Alternative names
    • Adapter protein CIKS
    • Connection to IKK and SAPK/JNK
    • E3 ubiquitin-protein ligase CIKS
    • Nuclear factor NF-kappa-B activator 1 (ACT1)
    • TRAF3-interacting protein 2

Gene names

    • Name
      TRAF3IP2
    • Synonyms
      C6orf2, C6orf4, C6orf5, C6orf6

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O43734
  • Secondary accessions
    • B2RAY9
    • E1P555
    • Q5R3A3
    • Q7Z6Q1
    • Q7Z6Q2

Proteomes

Organism-specific databases

Disease & Variants

Involvement in disease

Psoriasis 13 (PSORS13)

  • Note
    • Disease susceptibility is associated with variants affecting the gene represented in this entry
  • Description
    A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
  • See also
    MIM:614070

Candidiasis, familial, 8 (CANDF8)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
  • See also
    MIM:615527
Natural variants in CANDF8
Variant IDPosition(s)ChangeDescription
VAR_070904536T>Iin CANDF8; abolishes homotypic interactions with the SEFIR domain of IL17RA, IL17RB and IL17RC; does not affect homodimerization; does not affect SEFIR-independent interactions with other proteins; dbSNP:rs397518485

Features

Showing features for natural variant, mutagenesis.

Type
IDPosition(s)Description
Natural variantVAR_04734919likely risk factor for PSORS13; there is a reducing binding of this variant to TRAF6; dbSNP:rs33980500
Natural variantVAR_03122783in dbSNP:rs13190932
Mutagenesis303Loss of E3 ubiquitin ligase activity.
Mutagenesis318Decreases E3 ubiquitin ligase activity.
Mutagenesis319Loss of E3 ubiquitin ligase activity.
Mutagenesis324Decreases E3 ubiquitin ligase activity.
Natural variantVAR_024307332in dbSNP:rs1043730
Natural variantVAR_070904536in CANDF8; abolishes homotypic interactions with the SEFIR domain of IL17RA, IL17RB and IL17RC; does not affect homodimerization; does not affect SEFIR-independent interactions with other proteins; dbSNP:rs397518485

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 586 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data).

Type
IDPosition(s)Source
Description
ChainPRO_00000897511-574UniProtE3 ubiquitin ligase TRAF3IP2
Modified residue (large scale data)36PRIDEPhosphoserine
Modified residue (large scale data)383PRIDEPhosphoserine
Modified residue (large scale data)558PRIDEPhosphotyrosine

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with IKBKG/NF-kappa B essential modulator, with CHUK/IKK-alpha and with IKBKB/IKK-beta (PubMed:12459498).
Interacts with TRAF6; this interaction is direct (PubMed:12459498, PubMed:19825828).
Interacts with IL17RA and IL17RC (PubMed:19825828, PubMed:24120361, PubMed:33723527).
Interacts with IL17RB (PubMed:24120361).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntAct
BINARY O43734FHL3 Q96C983EBI-744798, EBI-10229248
BINARY O43734MRPL28 Q130843EBI-744798, EBI-723426
BINARY O43734RIMBP3 Q9UFD93EBI-744798, EBI-10182375
BINARY O43734STK16 O757163EBI-744798, EBI-749295
BINARY O43734TRAF6 Q9Y4K34EBI-744798, EBI-359276
BINARY O43734TRIP6 Q156543EBI-744798, EBI-742327

Complex viewer

View interactors in UniProtKB
View CPX-8776 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain.

Type
IDPosition(s)Description
Region1-67Disordered
Region1-256Mediates interaction with TRAF6
Compositional bias52-67Polar residues
Region155-211Disordered
Compositional bias170-186Polar residues
Region327-403Disordered
Compositional bias378-394Pro residues
Domain409-550SEFIR

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (5)
  • Sequence status
    Complete

This entry describes 5 isoforms produced by Alternative splicing.

O43734-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    C6ORF4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    574
  • Mass (Da)
    64,666
  • Last updated
    2011-01-11 v3
  • MD5 Checksum
    FEFA5D07A8E4A7D1F2D6241664011DF3
MPPQLQETRMNRSIPVEVDESEPYPSQLLKPIPEYSPEEESEPPAPNIRNMAPNSLSAPTMLHNSSGDFSQAHSTLKLANHQRPVSRQVTCLRTQVLEDSEDSFCRRHPGLGKAFPSGCSAVSEPASESVVGALPAEHQFSFMEKRNQWLVSQLSAASPDTGHDSDKSDQSLPNASADSLGGSQEMVQRPQPHRNRAGLDLPTIDTGYDSQPQDVLGIRQLERPLPLTSVCYPQDLPRPLRSREFPQFEPQRYPACAQMLPPNLSPHAPWNYHYHCPGSPDHQVPYGHDYPRAAYQQVIQPALPGQPLPGASVRGLHPVQKVILNYPSPWDHEERPAQRDCSFPGLPRHQDQPHHQPPNRAGAPGESLECPAELRPQVPQPPSPAAVPRPPSNPPARGTLKTSNLPEELRKVFITYSMDTAMEVVKFVNFLLVNGFQTAIDIFEDRIRGIDIIKWMERYLRDKTVMIIVAISPKYKQDVEGAESQLDEDEHGLHTKYIHRMMQIEFIKQGSMNFRFIPVLFPNAKKEHVPTWLQNTHVYSWPKNKKNILLRLLREEEYVAPPRGPLPTLQVVPL

O43734-2

  • Name
    2
  • Synonyms
    C6ORF5, C6ORF6
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-9: Missing

O43734-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

O43734-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

O43734-5

  • Name
    5
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8V8TQD6A0A8V8TQD6_HUMANTRAF3IP2585
A0A494C1J9A0A494C1J9_HUMANTRAF3IP2105
A0A494C0I3A0A494C0I3_HUMANTRAF3IP241
A0A494C0G2A0A494C0G2_HUMANTRAF3IP261
A0A494C0R7A0A494C0R7_HUMANTRAF3IP267

Sequence caution

The sequence BAB15507.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

Type
IDPosition(s)Description
Alternative sequenceVSP_0041631-9in isoform 2 and isoform 5
Alternative sequenceVSP_0357331-421in isoform 3
Alternative sequenceVSP_0403741-465in isoform 4
Compositional bias52-67Polar residues
Compositional bias170-186Polar residues
Sequence conflict334in Ref. 3; AAG15407
Sequence conflict347in Ref. 1; AAF67447
Compositional bias378-394Pro residues
Alternative sequenceVSP_047098463in isoform 5

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF136405
EMBL· GenBank· DDBJ
AAF67445.1
EMBL· GenBank· DDBJ
mRNA
AF136406
EMBL· GenBank· DDBJ
AAF67446.1
EMBL· GenBank· DDBJ
mRNA
AF136407
EMBL· GenBank· DDBJ
AAF67447.1
EMBL· GenBank· DDBJ
mRNA
AF274303
EMBL· GenBank· DDBJ
AAG15367.1
EMBL· GenBank· DDBJ
mRNA
AF272151
EMBL· GenBank· DDBJ
AAG15407.1
EMBL· GenBank· DDBJ
mRNA
AK025351
EMBL· GenBank· DDBJ
BAB15117.1
EMBL· GenBank· DDBJ
mRNA
AK026602
EMBL· GenBank· DDBJ
BAB15507.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK314415
EMBL· GenBank· DDBJ
BAG37036.1
EMBL· GenBank· DDBJ
mRNA
AL050289
EMBL· GenBank· DDBJ
CAB43390.1
EMBL· GenBank· DDBJ
mRNA
AL008730
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
Z97989
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471051
EMBL· GenBank· DDBJ
EAW48285.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471051
EMBL· GenBank· DDBJ
EAW48287.1
EMBL· GenBank· DDBJ
Genomic DNA
BC002823
EMBL· GenBank· DDBJ
AAH02823.1
EMBL· GenBank· DDBJ
mRNA
BI856094
EMBL· GenBank· DDBJ
-mRNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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