TRAF6

Functionⁱ

E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, 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. 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.11 Publications

Catalytic activityⁱ

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayⁱ: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	70 – 109	RING-typePROSITE-ProRule annotationAdd BLAST	40
Zinc fingerⁱ	150 – 202	TRAF-type 1PROSITE-ProRule annotationAdd BLAST	53
Zinc fingerⁱ	203 – 259	TRAF-type 2PROSITE-ProRule annotationAdd BLAST	57

GO - Molecular functionⁱ

histone deacetylase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 18093978
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
mitogen-activated protein kinase kinase kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 10094049
protein kinase B binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19713527
protein kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19713527
protein N-terminus binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 14530355
thioesterase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11279055
tumor necrosis factor receptor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11728344
ubiquitin conjugating enzyme binding
Source: MGI
Inferred from direct assayⁱ
- 23776175
ubiquitin protein ligase activity Source: Ensembl
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11279055
ubiquitin-protein transferase activity
Source: UniProtKB
Inferred from direct assayⁱ
zinc ion binding Source: InterPro

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of MAPK activity Source: Reactome
activation of NF-kappaB-inducing kinase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15125833
activation of protein kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 17135271
antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Ensembl
bone resorption Source: Ensembl
cell development Source: Ensembl
cellular response to DNA damage stimulus Source: UniProtKB-KW
cellular response to lipopolysaccharide
Source: MGI
Inferred from direct assayⁱ
- 23776175
Fc-epsilon receptor signaling pathway Source: Reactome
I-kappaB kinase/NF-kappaB signaling Source: Reactome
interleukin-1-mediated signaling pathway Source: Reactome
JNK cascade Source: Reactome
membrane protein intracellular domain proteolysis Source: Reactome
MyD88-dependent toll-like receptor signaling pathway Source: Reactome
myeloid dendritic cell differentiation Source: Ensembl
negative regulation of apoptotic process Source: Reactome
negative regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18093978
negative regulation of transcription by RNA polymerase II
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18093978
neural tube closure Source: Ensembl
nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
odontogenesis of dentin-containing tooth Source: Ensembl
ossification Source: UniProtKB-KW
osteoclast differentiation Source: Ensembl
positive regulation of apoptotic process Source: Reactome
positive regulation of DNA-binding transcription factor activity
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 12296995
positive regulation of I-kappaB kinase/NF-kappaB signaling
Source: UniProtKB
Inferred from direct assayⁱ
- 17135271
positive regulation of interleukin-12 biosynthetic process Source: Ensembl
positive regulation of interleukin-2 production
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15125833
positive regulation of interleukin-6 biosynthetic process Source: Ensembl
positive regulation of JUN kinase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 11751921
positive regulation of lipopolysaccharide-mediated signaling pathway Source: Ensembl
positive regulation of NF-kappaB transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 11279055
- 16378096
positive regulation of osteoclast differentiation
Source: UniProtKB
Inferred from direct assayⁱ
- 17135271
positive regulation of protein ubiquitination
Source: BHF-UCL
Non-traceable author statementⁱ
- 22412986
positive regulation of smooth muscle cell proliferation Source: Ensembl
positive regulation of T cell cytokine production
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15125833
positive regulation of T cell proliferation Source: Ensembl
positive regulation of transcription by RNA polymerase II
Source: BHF-UCL
Inferred from direct assayⁱ
- 11751921
positive regulation of transcription regulatory region DNA binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 11751921
protein autoubiquitination
Source: UniProtKB
Inferred from direct assayⁱ
- 17135271
- 18093978
protein deubiquitination Source: Reactome
protein K63-linked ubiquitination
Source: UniProtKB
Inferred from direct assayⁱ
- 19713527
protein polyubiquitination
Source: UniProtKB
Inferred from direct assayⁱ
- 15125833
- 19675569
regulation of immunoglobulin secretion Source: Ensembl
response to interleukin-1
Source: UniProtKB
Inferred from direct assayⁱ
- 17135271
stimulatory C-type lectin receptor signaling pathway Source: Reactome
T cell receptor signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 15125833
T-helper 1 type immune response Source: Ensembl
toll-like receptor 9 signaling pathway Source: Reactome
toll-like receptor signaling pathway Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Transferase
Biological process	DNA damage, Immunity, Osteogenesis, Ubl conjugation pathway
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-HSA-1257604 PIP3 activates AKT signaling R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168638 NOD1/2 Signaling Pathway R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment R-HSA-193692 Regulated proteolysis of p75NTR R-HSA-202424 Downstream TCR signaling R-HSA-205043 NRIF signals cell death from the nucleus R-HSA-209543 p75NTR recruits signalling complexes R-HSA-209560 NF-kB is activated and signals survival R-HSA-2871837 FCERI mediated NF-kB activation R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-450302 activated TAK1 mediates p38 MAPK activation R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-HSA-5607764 CLEC7A (Dectin-1) signaling R-HSA-5689880 Ub-specific processing proteases R-HSA-5689896 Ovarian tumor domain proteases R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex R-HSA-9020702 Interleukin-1 signaling R-HSA-933541 TRAF6 mediated IRF7 activation R-HSA-933542 TRAF6 mediated NF-kB activation R-HSA-937039 IRAK1 recruits IKK complex R-HSA-937041 IKK complex recruitment mediated by RIP1 R-HSA-937042 IRAK2 mediated activation of TAK1 complex R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation R-HSA-975871 MyD88 cascade initiated on plasma membrane
SignaLinkⁱ	Q9Y4K3
SIGNORⁱ	Q9Y4K3
UniPathwayⁱ	UPA00143

Protein family/group databases

MoonDBⁱ	Q9Y4K3 Predicted

MoonDBⁱ

Q9Y4K3 Predicted

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: TNF receptor-associated factor 6 (EC:2.3.2.27) Alternative name(s): E3 ubiquitin-protein ligase TRAF6 Interleukin-1 signal transducer RING finger protein 85 RING-type E3 ubiquitin transferase TRAF6Curated
Gene namesⁱ	Name:TRAF6 Synonyms:RNF85
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 11

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000175104.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12036 TRAF6
MIMⁱ	602355 gene
neXtProtⁱ	NX_Q9Y4K3

Keywords - Cellular componentⁱ

Cytoplasm, Lipid droplet, Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	57	D → K: Loss of interaction with UBE2N. 1 Publication	1
Mutagenesisⁱ	70	C → A: Loss of ligase activity, autoubiquitination and signaling capacity. 2 Publications	1
Mutagenesisⁱ	72	I → D: Loss of interaction with UBE2N. 1 Publication	1
Mutagenesisⁱ	74	L → E or K: Loss of interaction with UBE2N. 1 Publication	1
Mutagenesisⁱ	88	R → A: Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis. Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis; when associated with A-122. 1 Publication	1
Mutagenesisⁱ	118	F → A: Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis. 1 Publication	1
Mutagenesisⁱ	118	F → W: Partially impaired polyubiquitin synthesis. 1 Publication	1
Mutagenesisⁱ	118	F → Y: Partially impaired polyubiquitin synthesis. 1 Publication	1
Mutagenesisⁱ	122	F → A: Loss of TRAF6 homodimerization and partially impaired polyubiquitin synthesis. Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis; when associated with A-88. 1 Publication	1
Mutagenesisⁱ	124	K → R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation. 3 Publications	1
Mutagenesisⁱ	142	K → R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation. 1 Publication	1
Mutagenesisⁱ	453	K → R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	7189
MalaCards human disease database More...MalaCardsⁱ	TRAF6
Open Targets More...OpenTargetsⁱ	ENSG00000175104
Orphanetⁱ	1810 Autosomal dominant hypohidrotic ectodermal dysplasia
PharmGKBⁱ	PA36713

Chemistry databases

ChEMBLⁱ	CHEMBL3588728

ChEMBLⁱ

CHEMBL3588728

Polymorphism and mutation databases

BioMutaⁱ	TRAF6
DMDMⁱ	30580642

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000056407	1 – 522	TNF receptor-associated factor 6Add BLAST		522

Amino acid modifications

Feature key	Position(s)	DescriptionActions
Cross-linkⁱ	124	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linkⁱ	124	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Cross-linkⁱ	142	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linkⁱ	453	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationⁱ

Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1.1 Publication

Polyubiquitinated on Lys-124; after cell stimulation with IL-1-beta or TGF-beta. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage (PubMed:25861989).7 Publications

Keywords - PTMⁱ

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDⁱ	Q9Y4K3
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9Y4K3
PaxDbⁱ	Q9Y4K3
PeptideAtlas More...PeptideAtlasⁱ	Q9Y4K3
PRIDEⁱ	Q9Y4K3
ProteomicsDBⁱ	86225

PTM databases

iPTMnetⁱ	Q9Y4K3
PhosphoSitePlusⁱ	Q9Y4K3

Expressionⁱ

Tissue specificityⁱ

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Gene expression databases

Bgeeⁱ	ENSG00000175104 Expressed in 170 organ(s), highest expression level in secondary oocyte
CleanExⁱ	HS_TRAF6
Genevisibleⁱ	Q9Y4K3 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB004605 HPA019805 HPA020599

HPAⁱ

CAB004605
HPA019805
HPA020599

Interactionⁱ

Subunit structureⁱ

Homotrimer. Homooligomer. N-terminal region is dimeric while C-terminal region is trimeric; maybe providing a mode of oligomerization. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK. Associates with NGFR, TNFRSF17, IRAK2, IRAK3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ (By similarity). Interacts with PELI2 and PELI3. Binds UBE2V1. Interacts with TAX1BP1. Interacts with ZNF675. Interacts with ARRB1 and ARRB2. Interacts with MAP3K7 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF domains) with NUMBL (via C-terminal). Interacts with RBCK1. Interacts with TRAF3IP2. Interacts with LIMD1 (via LIM domains) (By similarity). Interacts with RSAD2/viperin (By similarity). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). Interacts with ZFAND5. Interacts with IL1RL1. Interacts with TRAFD1. Interacts with AJUBA. Interacts with MAVS/IPS1. Interacts (via TRAF domains) with WDR34 (via WD domains). Interacts with IFIT3 (via N-terminus). Interacts with TICAM2. Interacts with CARD14. Interacts with CD40 and MAP3K8; the interaction is required for ERK activation (By similarity). Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with USP10; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this interaction increases in response to DNA damage and is stimulated by TANK (PubMed:25861989). Interacts with WDFY3 (By similarity). Interacts with TRIM13 (PubMed:28087809). Interacts with GPS2 (By similarity).By similarity3 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
itself		10	EBI-359276,EBI-359276
	Q8V2D1	3	EBI-359276,EBI-8622036	From Human cytomegalovirus.
AMBRA1	Q9C0C7-3	2	EBI-359276,EBI-16042318
CD40	P25942	2	EBI-359276,EBI-525714
Ecsit	Q9QZH6	2	EBI-359276,EBI-527020	From Mus musculus.
EDARADD	Q8WWZ3	5	EBI-359276,EBI-2949647
IL1R1	P14778	2	EBI-359276,EBI-525905
IRAK1	P51617	2	EBI-359276,EBI-358664
MALT1	Q9UDY8	5	EBI-359276,EBI-1047372
MAP3K14	Q99558	2	EBI-359276,EBI-358011
MAP3K7	O43318	2	EBI-359276,EBI-358684
MEOX2	P50222	3	EBI-359276,EBI-748397
Ngfr	P07174	2	EBI-359276,EBI-1038810	From Rattus norvegicus.
PLEKHF2	Q9H8W4	3	EBI-359276,EBI-742388
POLI	Q9UNA4	3	EBI-359276,EBI-741774
RUSC1	Q9BVN2-2	2	EBI-359276,EBI-6257338
SPHK1	Q9NYA1	2	EBI-359276,EBI-985303
SQSTM1	Q13501	4	EBI-359276,EBI-307104
TAB2	Q9NYJ8	3	EBI-359276,EBI-358708
TAX1BP1	Q86VP1	8	EBI-359276,EBI-529518
TIFA	Q96CG3	6	EBI-359276,EBI-740711
TNIK	Q9UKE5	3	EBI-359276,EBI-1051794
TRAF1	Q13077	13	EBI-359276,EBI-359224
TRAF2	Q12933	10	EBI-359276,EBI-355744
TRAF3IP2	O43734	4	EBI-359276,EBI-744798
TRAF5	O00463	14	EBI-359276,EBI-523498
UBC	P0CG48	3	EBI-359276,EBI-3390054
UBE2D1	P51668	2	EBI-359276,EBI-743540
UBE2D2	P62837	4	EBI-359276,EBI-347677
UBE2D3	P61077	2	EBI-359276,EBI-348268
UBE2N	P61088	8	EBI-359276,EBI-1052908
UL37	P10221	3	EBI-359276,EBI-6880600	From Human herpesvirus 1 (strain 17).
ULK1	O75385	2	EBI-359276,EBI-908831
USP2	O75604	3	EBI-359276,EBI-743272
VACWR178	Q01220	2	EBI-359276,EBI-3863691	From Vaccinia virus (strain Western Reserve).
VPS52	Q8N1B4	5	EBI-359276,EBI-2799833
WDR5	P61964	2	EBI-359276,EBI-540834
XIAP	P98170	2	EBI-359276,EBI-517127
YES1	P07947	5	EBI-359276,EBI-515331
ZNF675	Q8TD23	4	EBI-359276,EBI-528190
ZRANB1	Q9UGI0	3	EBI-359276,EBI-527853

GO - Molecular functionⁱ

histone deacetylase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 18093978
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
mitogen-activated protein kinase kinase kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 10094049
protein kinase B binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19713527
protein kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19713527
protein N-terminus binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 14530355
thioesterase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11279055
tumor necrosis factor receptor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11728344
ubiquitin conjugating enzyme binding
Source: MGI
Inferred from direct assayⁱ
- 23776175
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11279055

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	113041, 303 interactors
CORUMⁱ	Q9Y4K3
Database of interacting proteins More...DIPⁱ	DIP-27515N
ELMⁱ	Q9Y4K3
IntActⁱ	Q9Y4K3, 113 interactors
Molecular INTeraction database More...MINTⁱ	Q9Y4K3
STRINGⁱ	9606.ENSP00000337853

Chemistry databases

BindingDBⁱ

Q9Y4K3

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	60 – 62	Combined sources	3
Helixⁱ	66 – 68	Combined sources	3
Turnⁱ	71 – 73	Combined sources	3
Beta strandⁱ	78 – 82	Combined sources	5
Turnⁱ	84 – 86	Combined sources	3
Beta strandⁱ	88 – 90	Combined sources	3
Helixⁱ	91 – 101	Combined sources	11
Turnⁱ	106 – 108	Combined sources	3
Helixⁱ	114 – 116	Combined sources	3
Helixⁱ	121 – 128	Combined sources	8
Beta strandⁱ	130 – 133	Combined sources	4
Beta strandⁱ	135 – 138	Combined sources	4
Beta strandⁱ	142 – 144	Combined sources	3
Helixⁱ	145 – 147	Combined sources	3
Helixⁱ	149 – 151	Combined sources	3
Beta strandⁱ	153 – 155	Combined sources	3
Beta strandⁱ	158 – 161	Combined sources	4
Turnⁱ	163 – 165	Combined sources	3
Beta strandⁱ	168 – 170	Combined sources	3
Helixⁱ	171 – 173	Combined sources	3
Helixⁱ	174 – 180	Combined sources	7
Beta strandⁱ	186 – 188	Combined sources	3
Turnⁱ	190 – 192	Combined sources	3
Beta strandⁱ	195 – 197	Combined sources	3
Helixⁱ	198 – 200	Combined sources	3
Helixⁱ	201 – 205	Combined sources	5
Beta strandⁱ	351 – 357	Combined sources	7
Helixⁱ	360 – 368	Combined sources	9
Beta strandⁱ	373 – 376	Combined sources	4
Beta strandⁱ	380 – 385	Combined sources	6
Beta strandⁱ	388 – 395	Combined sources	8
Turnⁱ	401 – 405	Combined sources	5
Beta strandⁱ	406 – 414	Combined sources	9
Helixⁱ	419 – 421	Combined sources	3
Beta strandⁱ	428 – 434	Combined sources	7
Helixⁱ	440 – 442	Combined sources	3
Beta strandⁱ	446 – 451	Combined sources	6
Helixⁱ	457 – 459	Combined sources	3
Beta strandⁱ	463 – 466	Combined sources	4
Beta strandⁱ	468 – 478	Combined sources	11
Helixⁱ	479 – 483	Combined sources	5
Turnⁱ	484 – 486	Combined sources	3
Beta strandⁱ	492 – 500	Combined sources	9

Show more details

3D structure databases

ProteinModelPortalⁱ	Q9Y4K3
SMRⁱ	Q9Y4K3
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q9Y4K3

EvolutionaryTraceⁱ

Q9Y4K3

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	350 – 499	MATHPROSITE-ProRule annotationAdd BLAST		150

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 354	Interaction with TAX1BP11 PublicationAdd BLAST		354
Regionⁱ	355 – 522	Interaction with TANK1 PublicationAdd BLAST		168

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	288 – 348	Sequence analysisAdd BLAST		61

Domainⁱ

The coiled coil domain mediates homo- and hetero-oligomerization.

The MATH/TRAF domain binds to receptor cytoplasmic domains.

Sequence similaritiesⁱ

Belongs to the TNF receptor-associated factor family. A subfamily.Curated

Zinc finger

Feature key	Position(s)	DescriptionActions	Length
Zinc fingerⁱ	70 – 109	RING-typePROSITE-ProRule annotationAdd BLAST	40
Zinc fingerⁱ	150 – 202	TRAF-type 1PROSITE-ProRule annotationAdd BLAST	53
Zinc fingerⁱ	203 – 259	TRAF-type 2PROSITE-ProRule annotationAdd BLAST	57

Keywords - Domainⁱ

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGⁱ	ENOG410ISDW Eukaryota ENOG410XTXK LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00550000074359
HOGENOMⁱ	HOG000006625
HOVERGENⁱ	HBG060248
InParanoidⁱ	Q9Y4K3
KEGG Orthology (KO) More...KOⁱ	K03175
OMAⁱ	IRQNHEE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0GHD
PhylomeDBⁱ	Q9Y4K3
TreeFamⁱ	TF321154

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd03776 MATH_TRAF6, 1 hit
Gene3Dⁱ	2.60.210.10, 1 hit 3.30.40.10, 3 hits
InterProⁱ	View protein in InterPro IPR002083 MATH/TRAF_dom IPR012227 TNF_rcpt--assoc_TRAF IPR008974 TRAF-like IPR027139 TRAF6 IPR037309 TRAF6_MATH IPR001841 Znf_RING IPR013083 Znf_RING/FYVE/PHD IPR017907 Znf_RING_CS IPR001293 Znf_TRAF
PANTHERⁱ	PTHR10131:SF111 PTHR10131:SF111, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02176 zf-TRAF, 1 hit
PIRSFⁱ	PIRSF015614 TRAF, 1 hit
SMARTⁱ	View protein in SMART SM00061 MATH, 1 hit SM00184 RING, 1 hit
SUPFAMⁱ	SSF49599 SSF49599, 3 hits
PROSITEⁱ	View protein in PROSITE PS50144 MATH, 1 hit PS00518 ZF_RING_1, 1 hit PS50089 ZF_RING_2, 1 hit PS50145 ZF_TRAF, 2 hits

Sequenceⁱ

Sequence statusⁱ: Complete.

Q9Y4K3-1 [UniParc]FASTA Add to basket

« Hide

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

Length:522

Mass (Da):59,573

Last modified:November 1, 1999 - v1

Checksum:ⁱ5AB9C255CCFEE749

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	12	S → F in AAH31052 (PubMed:15489334).Curated		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U78798 mRNA Translation: AAB38751.1 AY228337 Genomic DNA Translation: AAO38054.1 AK292978 mRNA Translation: BAF85667.1 AC009656 Genomic DNA No translation available. AC061999 Genomic DNA No translation available. CH471064 Genomic DNA Translation: EAW68119.1 CH471064 Genomic DNA Translation: EAW68120.1 CH471064 Genomic DNA Translation: EAW68122.1 BC031052 mRNA Translation: AAH31052.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS7901.1
PIRⁱ	S71821
NCBI Reference Sequences More...RefSeqⁱ	NP_004611.1, NM_004620.3 NP_665802.1, NM_145803.2
UniGeneⁱ	Hs.444172 Hs.591983

Genome annotation databases

Ensemblⁱ	ENST00000348124; ENSP00000337853; ENSG00000175104 ENST00000526995; ENSP00000433623; ENSG00000175104
GeneIDⁱ	7189
KEGGⁱ	hsa:7189
UCSC genome browser More...UCSCⁱ	uc001mwq.3 human

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9Y4K3	TNF receptor-associated factor 6		PIG		541	UniRef90_Q9Y4K3
TNF receptor-associated factor 6		CERAT		522
TNF receptor-associated factor 6		MACMU		522
TNF receptor associated factor 6		PONAB		604
TNF receptor-associated factor 6		PANTR		522
+58

Protein	Similar proteins		Species	Score	Length	Source
Q9Y4K3	TNF receptor-associated factor 6		PIG		541	UniRef50_Q9Y4K3
TNF receptor-associated factor 6		MACMU		522
TNF receptor-associated factor 6		CERAT		522
TNF receptor-associated factor 6		BOVIN		542
TNF receptor-associated factor 6		MOUSE		530
+167

Cross-referencesⁱ

Web resourcesⁱ

SeattleSNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U78798 mRNA Translation: AAB38751.1 AY228337 Genomic DNA Translation: AAO38054.1 AK292978 mRNA Translation: BAF85667.1 AC009656 Genomic DNA No translation available. AC061999 Genomic DNA No translation available. CH471064 Genomic DNA Translation: EAW68119.1 CH471064 Genomic DNA Translation: EAW68120.1 CH471064 Genomic DNA Translation: EAW68122.1 BC031052 mRNA Translation: AAH31052.1
CCDSⁱ	CCDS7901.1
PIRⁱ	S71821
RefSeqⁱ	NP_004611.1, NM_004620.3 NP_665802.1, NM_145803.2
UniGeneⁱ	Hs.444172 Hs.591983

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1LB4	X-ray	2.40	A	348-504	[»]
	1LB5	X-ray	2.40	A	347-504	[»]
	1LB6	X-ray	1.80	A	347-504	[»]
	2ECI	NMR	-	A	50-128	[»]
	2JMD	NMR	-	A	67-124	[»]
	3HCS	X-ray	2.20	A/B	50-211	[»]
	3HCT	X-ray	2.10	A	50-159	[»]
	3HCU	X-ray	2.60	A/C	50-159	[»]
	4Z8M	X-ray	2.95	A/B	346-504	[»]
ProteinModelPortalⁱ	Q9Y4K3
SMRⁱ	Q9Y4K3
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	113041, 303 interactors
CORUMⁱ	Q9Y4K3
DIPⁱ	DIP-27515N
ELMⁱ	Q9Y4K3
IntActⁱ	Q9Y4K3, 113 interactors
MINTⁱ	Q9Y4K3
STRINGⁱ	9606.ENSP00000337853

Chemistry databases

BindingDBⁱ	Q9Y4K3
ChEMBLⁱ	CHEMBL3588728

Protein family/group databases

MoonDBⁱ	Q9Y4K3 Predicted

MoonDBⁱ

Q9Y4K3 Predicted

PTM databases

iPTMnetⁱ	Q9Y4K3
PhosphoSitePlusⁱ	Q9Y4K3

Polymorphism and mutation databases

BioMutaⁱ	TRAF6
DMDMⁱ	30580642

Proteomic databases

EPDⁱ	Q9Y4K3
MaxQBⁱ	Q9Y4K3
PaxDbⁱ	Q9Y4K3
PeptideAtlasⁱ	Q9Y4K3
PRIDEⁱ	Q9Y4K3
ProteomicsDBⁱ	86225

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	7189
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000348124; ENSP00000337853; ENSG00000175104 ENST00000526995; ENSP00000433623; ENSG00000175104
GeneIDⁱ	7189
KEGGⁱ	hsa:7189
UCSCⁱ	uc001mwq.3 human

Organism-specific databases

CTDⁱ	7189
DisGeNETⁱ	7189
EuPathDBⁱ	HostDB:ENSG00000175104.14
GeneCardsⁱ	TRAF6
HGNCⁱ	HGNC:12036 TRAF6
HPAⁱ	CAB004605 HPA019805 HPA020599
MalaCardsⁱ	TRAF6
MIMⁱ	602355 gene
neXtProtⁱ	NX_Q9Y4K3
OpenTargetsⁱ	ENSG00000175104
Orphanetⁱ	1810 Autosomal dominant hypohidrotic ectodermal dysplasia
PharmGKBⁱ	PA36713
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410ISDW Eukaryota ENOG410XTXK LUCA
GeneTreeⁱ	ENSGT00550000074359
HOGENOMⁱ	HOG000006625
HOVERGENⁱ	HBG060248
InParanoidⁱ	Q9Y4K3
KOⁱ	K03175
OMAⁱ	IRQNHEE
OrthoDBⁱ	EOG091G0GHD
PhylomeDBⁱ	Q9Y4K3
TreeFamⁱ	TF321154

Enzyme and pathway databases

UniPathwayⁱ	UPA00143
Reactomeⁱ	R-HSA-1257604 PIP3 activates AKT signaling R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168638 NOD1/2 Signaling Pathway R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment R-HSA-193692 Regulated proteolysis of p75NTR R-HSA-202424 Downstream TCR signaling R-HSA-205043 NRIF signals cell death from the nucleus R-HSA-209543 p75NTR recruits signalling complexes R-HSA-209560 NF-kB is activated and signals survival R-HSA-2871837 FCERI mediated NF-kB activation R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-450302 activated TAK1 mediates p38 MAPK activation R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-HSA-5607764 CLEC7A (Dectin-1) signaling R-HSA-5689880 Ub-specific processing proteases R-HSA-5689896 Ovarian tumor domain proteases R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex R-HSA-9020702 Interleukin-1 signaling R-HSA-933541 TRAF6 mediated IRF7 activation R-HSA-933542 TRAF6 mediated NF-kB activation R-HSA-937039 IRAK1 recruits IKK complex R-HSA-937041 IKK complex recruitment mediated by RIP1 R-HSA-937042 IRAK2 mediated activation of TAK1 complex R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation R-HSA-975871 MyD88 cascade initiated on plasma membrane
SignaLinkⁱ	Q9Y4K3
SIGNORⁱ	Q9Y4K3

Miscellaneous databases

ChiTaRSⁱ	TRAF6 human
EvolutionaryTraceⁱ	Q9Y4K3
GeneWikiⁱ	TRAF6
GenomeRNAiⁱ	7189
Protein Ontology More...PROⁱ	PR:Q9Y4K3
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000175104 Expressed in 170 organ(s), highest expression level in secondary oocyte
CleanExⁱ	HS_TRAF6
Genevisibleⁱ	Q9Y4K3 HS

Family and domain databases

CDDⁱ	cd03776 MATH_TRAF6, 1 hit
Gene3Dⁱ	2.60.210.10, 1 hit 3.30.40.10, 3 hits
InterProⁱ	View protein in InterPro IPR002083 MATH/TRAF_dom IPR012227 TNF_rcpt--assoc_TRAF IPR008974 TRAF-like IPR027139 TRAF6 IPR037309 TRAF6_MATH IPR001841 Znf_RING IPR013083 Znf_RING/FYVE/PHD IPR017907 Znf_RING_CS IPR001293 Znf_TRAF
PANTHERⁱ	PTHR10131:SF111 PTHR10131:SF111, 1 hit
Pfamⁱ	View protein in Pfam PF02176 zf-TRAF, 1 hit
PIRSFⁱ	PIRSF015614 TRAF, 1 hit
SMARTⁱ	View protein in SMART SM00061 MATH, 1 hit SM00184 RING, 1 hit
SUPFAMⁱ	SSF49599 SSF49599, 3 hits
PROSITEⁱ	View protein in PROSITE PS50144 MATH, 1 hit PS00518 ZF_RING_1, 1 hit PS50089 ZF_RING_2, 1 hit PS50145 ZF_TRAF, 2 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TRAF6_HUMAN
Accessionⁱ	Q9Y4K3Primary (citable) accession number: Q9Y4K3 Secondary accession number(s): A6NKI7 , A8KAB3, D3DR16, Q8NEH5
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
	Last sequence update:	November 1, 1999
	Last modified:	November 7, 2018
	This is version 210 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q9Y4K3 (TRAF6_HUMAN)

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TNF receptor-associated factor 6

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Cytosol

Endosome

Nucleus

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Your basket is currently empty. ⁱ

Functionⁱ

Pathwayⁱ: protein ubiquitination

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ