A7XUJ6 (TRAF6_PIG) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TNF receptor-associated factor 6
EC=6.3.2.-

Alternative name(s):
E3 ubiquitin-protein ligase TRAF6

Gene names

Name:

TRAF6

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	541 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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. Mediates 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 By similarity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homotrimer By similarity. Homooligomer By similarity. 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. Interacts with PELI2 and PELI3. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1. Interacts with IL1RL1. Interacts with TRAFD1. Interacts with ZNF675. Interacts with AJUBA. Interacts with TICAM1 and TICAM2. Interacts with ZFAND5. 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 (via TRAF domains) with WDR34 (via WD domains). Interacts with RBCK1 By similarity. Interacts with TRAF3IP2 By similarity. Interacts with LIMD1 (via LIM domains) By similarity. Interacts with RSAD2/viperin By similarity. Interacts with IFIT3 (via N-terminus) By similarity.
Subcellular location	Cytoplasm By similarity. Cytoplasm › cell cortex By similarity. Nucleus By similarity. Lipid droplet By similarity. Note: RSAD2/viperin recruits it to the lipid droplet By similarity.
Domain	The coiled coil domain mediates homo- and hetero-oligomerization By similarity. The MATH/TRAF domain binds to receptor cytoplasmic domains By similarity.
Post-translational modification	Sumoylated on Lys-125, Lys-143 and Lys-472 with SUMO1 By similarity. Polyubiquitinated; 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 By similarity.
Sequence similarities	Belongs to the TNF receptor-associated factor family. A subfamily. Contains 1 MATH domain. Contains 1 RING-type zinc finger. Contains 2 TRAF-type zinc fingers.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Lipid droplet Nucleus
Disease	Osteopetrosis
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Inferred from electronic annotation. Source: InterPro activation of NF-kappaB-inducing kinase activity Inferred from electronic annotation. Source: InterPro bone remodeling Inferred from electronic annotation. Source: InterPro cell development Inferred from electronic annotation. Source: InterPro interleukin-1-mediated signaling pathway Inferred from electronic annotation. Source: InterPro organ morphogenesis Inferred from electronic annotation. Source: InterPro ossification Inferred from electronic annotation. Source: InterPro positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: InterPro positive regulation of JUN kinase activity Inferred from electronic annotation. Source: InterPro positive regulation of lipopolysaccharide-mediated signaling pathway Inferred from electronic annotation. Source: InterPro positive regulation of osteoclast differentiation Inferred from electronic annotation. Source: InterPro protein K63-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB protein autoubiquitination Inferred from electronic annotation. Source: InterPro regulation of apoptotic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell lipid particle Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	signal transducer activity Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 541	541	TNF receptor-associated factor 6		PRO_0000391610
Regions
	Domain	369 – 518	150	MATH
	Zinc finger	71 – 110	40	RING-type; degenerate
	Zinc finger	151 – 203	53	TRAF-type 1
	Zinc finger	204 – 260	57	TRAF-type 2
	Region	1 – 373	373	Interaction with TAX1BP1 By similarity
	Coiled coil	312 – 367	56	Potential
Amino acid modifications
	Cross-link	125		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
	Cross-link	125		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
	Cross-link	143		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	472		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	A7XUJ6 [UniParc]. Last modified October 23, 2007. Version 1. Checksum: CCA939106D3476BE	FASTA	541	61,266
	10 20 30 40 50 60 MSLLHCENSC GSSQSESDCC AAMAASSCGA AAKDDGVSGT ASTGNLSSSF MEEIQGYDVE 70 80 90 100 110 120 FDPPLESKYE CPICLMALRE AVQTPCGHRF CKACIIKSIR DAGHKCPVDN EILLENQLFP 130 140 150 160 170 180 DNFAKREILS LTVKCPNVGC LHKMELRHLE DHQAHCEFAL MNCPQCQRPF QKCQLNIHIL 190 200 210 220 230 240 KECPRRQVSC VNCAVSMAFE DKEIHDQNCP LANVICEYCN TVLIREQMPN HYDLDCPTAP 250 260 270 280 290 300 VPCTFSTFGC HEKMQRNHLA RHLQENTQSH MRMMAQALQG LSLAVAPVPQ RDMLPYDSSP 310 320 330 340 350 360 LSRISSGCCS DQNFQETIQQ LEGRLVRQDH QIRELTAKME TQSMYVSELK RTIRSLEDKV 370 380 390 400 410 420 AEIEAQQCNG IYIWKIGNFG MHLKSQEEEK PVVIHSPGFY TGKPGYKLCM RLHLQLPTAQ 430 440 450 460 470 480 RCANYISLFV HTMQGEYDSH LPWPFQGTIR LTILDQSEAP IRQNHEEIMD AKPELLAFQR 490 500 510 520 530 540 PTIPRNPKGF GYVTFMHLDA LRQRTFIKDD TLLVRCEVST RFDMGSLRRE GFQPRSTDSG T

References

[1]	Wang D., Xiao S., Fang L. Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	EU095967 mRNA. Translation: ABU75303.1.
RefSeq	NP_001098756.1. NM_001105286.1.
UniGene	Ssc.96412.
3D structure databases
ProteinModelPortal	A7XUJ6.
SMR	A7XUJ6. Positions 44-129, 366-520.
ModBase	Search...
Protein-protein interaction databases
STRING	9823.ENSSSCP00000014123.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSSSCT00000014516; ENSSSCP00000014123; ENSSSCG00000013291. ENSSSCT00000033074; ENSSSCP00000029003; ENSSSCG00000013291.
GeneID	396629.
KEGG	ssc:396629.
Organism-specific databases
CTD	7189.
Phylogenomic databases
eggNOG	NOG289765.
GeneTree	ENSGT00550000074359.
HOGENOM	HOG000006625.
HOVERGEN	HBG060248.
KO	K03175.
OMA	SEAPIRQ.
OrthoDB	EOG4320XV.
Enzyme and pathway databases
UniPathway	UPA00143.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
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. [Graphical view]
PANTHER	PTHR10131:SF48. PTHR10131:SF48. 1 hit.
Pfam	PF00917. MATH. 1 hit. [Graphical view]
PIRSF	PIRSF015614. TRAF. 1 hit.
SMART	SM00061. MATH. 1 hit. SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF49599. Traf_like. 3 hits.
PROSITE	PS50144. MATH. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. PS50145. ZF_TRAF. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TRAF6_PIG

Accession

Primary (citable) accession number: A7XUJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 9, 2010
Last sequence update:	October 23, 2007
Last modified:	May 1, 2013
This is version 50 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program