Search Results

Overview

Uniprot ID	Q9Y4K3
Protein Name	TNF receptor-associated factor 6
Gene Name	TRAF6
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
489	LRQRTFIKDDTLLVR

Function

E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (PubMed:11057907, PubMed:18347055, PubMed:19465916, PubMed:19713527, PubMed:27746020, PubMed:31620128). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (PubMed:19675569). Leads to the activation of NF-kappa-B and JUN (PubMed:16378096, PubMed:17135271, PubMed:17703191, PubMed:39920527). Seems to also play a role in dendritic cells (DCs) maturation and/or activation (By similarity). Represses c-Myb-mediated transactivation, in B-lymphocytes (PubMed:18093978, PubMed:18758450). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor (PubMed:12140561, PubMed:19825828, PubMed:8837778). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (By similarity). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (By similarity). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by initiating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: TRAF6 catalyzes initial 'Lys-63'-linked-polyubiquitin chains that are then branched via 'Lys-48'-linked polyubiquitin by HUWE1 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Participates also in the TCR signaling by ubiquitinating LAT (PubMed:23514740, PubMed:25907557)

Protein Sequence

10 MSLLNCENSC 20 GSSQSESDCC 30 VAMASSCSAV 40 TKDDSVGGTA 50 STGNLSSSFM 60 EEIQGYDVEF 70 DPPLESKYEC 80 PICLMALREA 90 VQTPCGHRFC 100 KACIIKSIRD 110 AGHKCPVDNE 120 ILLENQLFPD 130 NFAKREILSL 140 MVKCPNEGCL 150 HKMELRHLED 160 HQAHCEFALM 170 DCPQCQRPFQ 180 KFHINIHILK 190 DCPRRQVSCD 200 NCAASMAFED 210 KEIHDQNCPL 220 ANVICEYCNT 230 ILIREQMPNH 240 YDLDCPTAPI 250 PCTFSTFGCH 260 EKMQRNHLAR 270 HLQENTQSHM 280 RMLAQAVHSL 290 SVIPDSGYIS 300 EVRNFQETIH 310 QLEGRLVRQD 320 HQIRELTAKM 330 ETQSMYVSEL 340 KRTIRTLEDK 350 VAEIEAQQCN 360 GIYIWKIGNF 370 GMHLKCQEEE 380 KPVVIHSPGF 390 YTGKPGYKLC 400 MRLHLQLPTA 410 QRCANYISLF 420 VHTMQGEYDS 430 HLPWPFQGTI 440 RLTILDQSEA 450 PVRQNHEEIM 460 DAKPELLAFQ 470 RPTIPRNPKG 480 FGYVTFMHLE 490 ALRQRTFIKD 500 DTLLVRCEVS 510 TRFDMGSLRR 520 EGFQPRSTDA GV

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0035631	CD40 receptor complex
Cellular Component	GO:0005938	cell cortex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0009898	cytoplasmic side of plasma membrane
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0010008	endosome membrane
Cellular Component	GO:0031234	extrinsic component of cytoplasmic side of plasma membrane
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0005811	lipid droplet
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0032991	protein-containing complex
Molecular Function	GO:0042826	histone deacetylase binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0043422	protein kinase B binding
Molecular Function	GO:0030674	protein-macromolecule adaptor activity
Molecular Function	GO:0035591	signaling adaptor activity
Molecular Function	GO:0005164	tumor necrosis factor receptor binding
Molecular Function	GO:0031624	ubiquitin conjugating enzyme binding
Molecular Function	GO:0061630	ubiquitin protein ligase activity
Molecular Function	GO:0004842	ubiquitin-protein transferase activity
Molecular Function	GO:0034450	ubiquitin-ubiquitin ligase activity
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0140374	antiviral innate immune response
Biological Process	GO:0000045	autophagosome assembly
Biological Process	GO:0045453	bone resorption
Biological Process	GO:0007249	canonical NF-kappaB signal transduction
Biological Process	GO:0023035	CD40 signaling pathway
Biological Process	GO:0071345	cellular response to cytokine stimulus
Biological Process	GO:0071222	cellular response to lipopolysaccharide
Biological Process	GO:0002753	cytoplasmic pattern recognition receptor signaling pathway
Biological Process	GO:0006974	DNA damage response
Biological Process	GO:0038095	Fc-epsilon receptor signaling pathway
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0070498	interleukin-1-mediated signaling pathway
Biological Process	GO:0097400	interleukin-17-mediated signaling pathway
Biological Process	GO:0038173	interleukin-17A-mediated signaling pathway
Biological Process	GO:0038172	interleukin-33-mediated signaling pathway
Biological Process	GO:0031663	lipopolysaccharide-mediated signaling pathway
Biological Process	GO:0002755	MyD88-dependent toll-like receptor signaling pathway
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0000122	negative regulation of transcription by RNA polymerase II
Biological Process	GO:0001843	neural tube closure
Biological Process	GO:0038061	non-canonical NF-kappaB signal transduction
Biological Process	GO:0001503	ossification
Biological Process	GO:0030316	osteoclast differentiation
Biological Process	GO:0043123	positive regulation of canonical NF-kappaB signal transduction
Biological Process	GO:0032743	positive regulation of interleukin-2 production
Biological Process	GO:0046330	positive regulation of JNK cascade
Biological Process	GO:1904996	positive regulation of leukocyte adhesion to vascular endothelial cell
Biological Process	GO:0031666	positive regulation of lipopolysaccharide-mediated signaling pathway
Biological Process	GO:0045672	positive regulation of osteoclast differentiation
Biological Process	GO:0031398	positive regulation of protein ubiquitination
Biological Process	GO:0002726	positive regulation of T cell cytokine production
Biological Process	GO:0042102	positive regulation of T cell proliferation
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0032481	positive regulation of type I interferon production
Biological Process	GO:0051865	protein autoubiquitination
Biological Process	GO:0141198	protein branched polyubiquitination
Biological Process	GO:0070534	protein K63-linked ubiquitination
Biological Process	GO:0000209	protein polyubiquitination
Biological Process	GO:0042981	regulation of apoptotic process
Biological Process	GO:0043122	regulation of canonical NF-kappaB signal transduction
Biological Process	GO:0098696	regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
Biological Process	GO:0070555	response to interleukin-1
Biological Process	GO:0002223	stimulatory C-type lectin receptor signaling pathway
Biological Process	GO:0050852	T cell receptor signaling pathway
Biological Process	GO:0034138	toll-like receptor 3 signaling pathway
Biological Process	GO:0034142	toll-like receptor 4 signaling pathway
Biological Process	GO:0035666	TRIF-dependent toll-like receptor signaling pathway
Biological Process	GO:0033209	tumor necrosis factor-mediated signaling pathway

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.