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Protein

TNF receptor-associated factor 6

Gene

TRAF6

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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. 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. 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

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 keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri70 – 109RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri150 – 202TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri203 – 259TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, Immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
TNF receptor-associated factor 6 (EC:2.3.2.27)
Alternative name(s):
E3 ubiquitin-protein ligase TRAF6
RING-type E3 ubiquitin transferase TRAF6Curated
Gene namesi
Name:TRAF6
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Chromosome 14

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Lipid droplet, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Osteopetrosis

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003916091 – 522TNF receptor-associated factor 6Add BLAST522

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki453Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Sumoylated on Lys-124, Lys-142 and Lys-453 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. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage.By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Expressioni

Gene expression databases

ExpressionAtlasiB6CJY5. baseline.

Interactioni

Subunit structurei

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 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). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with CARD14 (By similarity). Interacts with CD40 and MAP3K8; the interaction is required for ERK activation. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity). Interacts with TANK; this interaction increases in response to DNA damage (By similarity). Interacts with USP10; this interaction increases in response to DNA damage (By similarity). Interacts with ZC3H12A; this interaction increases in response to DNA damage and is stimulated by TANK (By similarity). Interacts with WDFY3 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000021907.

Structurei

3D structure databases

SMRiB6CJY5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini350 – 499MATHPROSITE-ProRule annotationAdd BLAST150

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 354Interaction with TAX1BP1By similarityAdd BLAST354
Regioni355 – 522Interaction with TANKBy similarityAdd BLAST168

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili288 – 348Sequence analysisAdd BLAST61

Domaini

The coiled coil domain mediates homo- and hetero-oligomerization.By similarity
The MATH/TRAF domain binds to receptor cytoplasmic domains.By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri70 – 109RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri150 – 202TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri203 – 259TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ISDW. Eukaryota.
ENOG410XTXK. LUCA.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiB6CJY5.
KOiK03175.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 4 hits.
InterProiView protein in InterPro
IPR002083. MATH/TRAF_dom.
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.
PANTHERiPTHR10131:SF111. PTHR10131:SF111. 1 hit.
PfamiView protein in Pfam
PF02176. zf-TRAF. 1 hit.
PIRSFiPIRSF015614. TRAF. 1 hit.
SMARTiView protein in SMART
SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
SUPFAMiSSF49599. SSF49599. 3 hits.
PROSITEiView 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.

B6CJY5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLNCENSC GSSQSESDCC VAMASSCSAA TKDDSVGGTA STGNLSSSFM
60 70 80 90 100
EDIQGYDVEF DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD
110 120 130 140 150
AGHKCPVDNE ILLENQLFPD NFAKREILSL MVKCPNEGCL HKMELRHLED
160 170 180 190 200
HQAHCEFALV DCPQCQRPFQ KFHINIHILK DCPRRQVSCD NCAALVAFED
210 220 230 240 250
KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI PCTFSTFGCH
260 270 280 290 300
EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SLIPDSGYVS EVRNFQETIH
310 320 330 340 350
QLEGRLVRQD HQIRELTAKM ETQSTYVSEL 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
DAKPDLLAFQ RPTIPRNPKG FGYVTFMHLE ALRQRTFIKD DTLLVRCEVS
510 520
TRFDMGSLRR EGFQPRSTDS GV
Length:522
Mass (Da):59,465
Last modified:November 25, 2008 - v1
Checksum:iC96138B2C75D93DB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU204929 mRNA. Translation: ABY64983.1.
RefSeqiNP_001129268.1. NM_001135796.1.
UniGeneiMmu.17706.

Genome annotation databases

EnsembliENSMMUT00000025667; ENSMMUP00000024012; ENSMMUG00000018266.
GeneIDi716907.
KEGGimcc:716907.

Similar proteinsi

Entry informationi

Entry nameiTRAF6_MACMU
AccessioniPrimary (citable) accession number: B6CJY5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 9, 2010
Last sequence update: November 25, 2008
Last modified: October 25, 2017
This is version 76 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families