CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023851
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 TNF receptor-associated factor 6 
Protein Synonyms/Alias
 E3 ubiquitin-protein ligase TRAF6; Interleukin-1 signal transducer; RING finger protein 85 
Gene Name
 TRAF6 
Gene Synonyms/Alias
 RNF85 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
124LFPDNFAKREILSLMsumoylation[1]
124LFPDNFAKREILSLMubiquitination[2]
142PNEGCLHKMELRHLEsumoylation[1]
331SMYVSELKRTIRTLEubiquitination[3, 4]
453HEEIMDAKPELLAFQsumoylation[1]
489LRQRTFIKDDTLLVRubiquitination[4]
Reference
 [1] Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification.
 Pham LV, Zhou HJ, Lin-Lee YC, Tamayo AT, Yoshimura LC, Fu L, Darnay BG, Ford RJ.
 J Biol Chem. 2008 Feb 22;283(8):5081-9. [PMID: 18093978]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF- kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL- 1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. 
Sequence Annotation
 DOMAIN 350 499 MATH.
 ZN_FING 70 109 RING-type.
 ZN_FING 150 202 TRAF-type 1.
 ZN_FING 203 259 TRAF-type 2.
 REGION 1 354 Interaction with TAX1BP1.
 CROSSLNK 124 124 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 124 124 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 142 142 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 453 453 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Coiled coil; Complete proteome; Cytoplasm; Isopeptide bond; Ligase; Lipid droplet; Metal-binding; Nucleus; Osteogenesis; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 522 AA 
Protein Sequence
MSLLNCENSC GSSQSESDCC VAMASSCSAV TKDDSVGGTA STGNLSSSFM EEIQGYDVEF 60
DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD AGHKCPVDNE ILLENQLFPD 120
NFAKREILSL MVKCPNEGCL HKMELRHLED HQAHCEFALM DCPQCQRPFQ KFHINIHILK 180
DCPRRQVSCD NCAASMAFED KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI 240
PCTFSTFGCH EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SVIPDSGYIS EVRNFQETIH 300
QLEGRLVRQD HQIRELTAKM ETQSMYVSEL KRTIRTLEDK VAEIEAQQCN GIYIWKIGNF 360
GMHLKCQEEE KPVVIHSPGF YTGKPGYKLC MRLHLQLPTA QRCANYISLF VHTMQGEYDS 420
HLPWPFQGTI RLTILDQSEA PVRQNHEEIM DAKPELLAFQ RPTIPRNPKG FGYVTFMHLE 480
ALRQRTFIKD DTLLVRCEVS TRFDMGSLRR EGFQPRSTDA GV 522 
Gene Ontology
 GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
 GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0010008; C:endosome membrane; TAS:Reactome.
 GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
 GO:0005811; C:lipid particle; ISS:UniProtKB.
 GO:0031965; C:nuclear membrane; IDA:HPA.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB.
 GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IEA:Compara.
 GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
 GO:0045453; P:bone resorption; IEA:Compara.
 GO:0048468; P:cell development; IEA:Compara.
 GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0070498; P:interleukin-1-mediated signaling pathway; IEA:Compara.
 GO:0007254; P:JNK cascade; TAS:Reactome.
 GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043011; P:myeloid dendritic cell differentiation; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0001843; P:neural tube closure; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Compara.
 GO:0001503; P:ossification; IEA:UniProtKB-KW.
 GO:0030316; P:osteoclast differentiation; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0045084; P:positive regulation of interleukin-12 biosynthetic process; IEA:Compara.
 GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
 GO:0045410; P:positive regulation of interleukin-6 biosynthetic process; IEA:Compara.
 GO:0043507; P:positive regulation of JUN kinase activity; NAS:UniProtKB.
 GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0045672; P:positive regulation of osteoclast differentiation; IDA:UniProtKB.
 GO:0031398; P:positive regulation of protein ubiquitination; NAS:BHF-UCL.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0050870; P:positive regulation of T cell activation; IC:UniProtKB.
 GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB.
 GO:0042102; P:positive regulation of T cell proliferation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0006461; P:protein complex assembly; IEA:Compara.
 GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
 GO:0051023; P:regulation of immunoglobulin secretion; IEA:Compara.
 GO:0070555; P:response to interleukin-1; IDA:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
 GO:0042088; P:T-helper 1 type immune response; IEA:Compara.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR002083; MATH.
 IPR012227; TNF_rcpt--assoc_TRAF.
 IPR008974; TRAF-like.
 IPR027139; TRAF6.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS.
 IPR001293; Znf_TRAF. 
Pfam
 PF00917; MATH 
SMART
 SM00061; MATH
 SM00184; RING 
PROSITE
 PS50144; MATH
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2
 PS50145; ZF_TRAF 
PRINTS