Descriptions

The Tumor Necrosis Factor (TNF) Receptor Associated Factor (TRAF) class of intracellular signal transducers is responsible for mediating many of the activation events initiated by TNF receptor (TNFR) and Toll-like/Interleukin-1, 17 and 18 receptor (TIR) families. ​​These receptors can, both directly and indirectly, activate TRAF6 via specific binding of proteins containing TRAF Interacting Motif (TIM) peptides to a groove on the carboxyl-terminal MATH domain. <br>TRAF6 is autoinhibited by an intramolecular interaction between the RING-Zinc (RZ) region and MATH domain. The interaction renders TRAF6 inactive and structurally closed, as well as incapable of auto-ubiquitination. RING-Zinc fingers region and the MATH domain are targets for ubiquitination. TRAF autoubiquitination in trans is a means of sustaining an open conformation active in downstream signaling.

Autoinhibitory domains (AIDs)

Target domain

71-274 (RZ domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

4 structures for Q6IWL4

Entry ID Method Resolution Chain Position Source
5VNZ X-ray 341 A A/D 50-159 PDB
5VO0 X-ray 390 A A/D 50-213 PDB
6MYD X-ray 140 A A/C 370-525 PDB
AF-Q6IWL4-F1 Predicted AlphaFoldDB

No variants for Q6IWL4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q6IWL4

No associated diseases with Q6IWL4

9 regional properties for Q6IWL4

Type Name Position InterPro Accession
domain Zinc finger, TRAF-type 132 - 178 IPR001293-1
domain Zinc finger, TRAF-type 205 - 262 IPR001293-2
domain Zinc finger, RING-type 71 - 110 IPR001841
domain MATH/TRAF domain 374 - 520 IPR002083
conserved_site Zinc finger, RING-type, conserved site 86 - 95 IPR017907
domain Zinc finger, C3HC4 RING-type 71 - 108 IPR018957
domain TNF receptor-associated factor 6, C3HC3D-type RING zinc finger 68 - 125 IPR027139
domain TNF receptor-associated factor 6, MATH domain 375 - 521 IPR037309
domain TRAF1-6, MATH domain 398 - 517 IPR049342

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
  • Cytoplasm
  • Cytoplasm, cell cortex
  • Nucleus
  • Lipid droplet
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cell cortex The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
lipid droplet An intracellular non-membrane-bounded organelle comprising a matrix of coalesced lipids surrounded by a phospholipid monolayer. May include associated proteins.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

4 GO annotations of molecular function

Name Definition
tumor necrosis factor receptor binding Binding to a tumor necrosis factor receptor.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond
ubiquitin-protein transferase activity Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.
zinc ion binding Binding to a zinc ion (Zn).

10 GO annotations of biological process

Name Definition
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
lipopolysaccharide-mediated signaling pathway The series of molecular signals initiated by the binding of a lipopolysaccharide (LPS) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Lipopolysaccharides are major components of the outer membrane of Gram-negative bacteria, making them prime targets for recognition by the immune system.
non-canonical NF-kappaB signal transduction The process in which a signal is passed on to downstream components within the cell through the NIK-dependent processing and activation of NF-KappaB. Begins with activation of the NF-KappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-Kappa B2 protein (p100) leading to p100 processing and release of an active NF-KappaB (p52).
positive regulation of DNA-templated transcription Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
protein K63-linked ubiquitination A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair.
regulation of apoptotic process Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of canonical NF-kappaB signal transduction Any process that modulates I-kappaB kinase/NF-kappaB signaling.
response to bacterium Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium.
response to virus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus.
tumor necrosis factor-mediated signaling pathway The series of molecular signals initiated by tumor necrosis factor binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.

7 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3ZCC3 TRAF6 TNF receptor-associated factor 6 Bos taurus (Bovine) SS
Q9Y4K3 TRAF6 TNF receptor-associated factor 6 Homo sapiens (Human) EV
P70196 Traf6 TNF receptor-associated factor 6 Mus musculus (Mouse) SS
A7XUJ6 TRAF6 TNF receptor-associated factor 6 Sus scrofa (Pig) SS
B5DF45 Traf6 TNF receptor-associated factor 6 Rattus norvegicus (Rat) SS
B6CJY5 TRAF6 TNF receptor-associated factor 6 Macaca mulatta (Rhesus macaque) SS
Q28DL4 traf6 TNF receptor-associated factor 6 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
10 20 30 40 50 60
MACNDVDKSS FDDVCCDSGH SSCAAAMEKE RESFLSPTEN PSTISVSSSM PPDQQGYDVE
70 80 90 100 110 120
FDPPLESKYE CPICLMGLRS AVQTPCGHRF CDSCIRKSIR DTGQKCPVDN EVLLEEQLFP
130 140 150 160 170 180
DNFAKREILS LTVKCSNFGC SEKMELRQLE KHLSQCRFAT APCPQCQESV PISHLDEHKS
190 200 210 220 230 240
QHCLQRIMTC PDCAGSFVYA VKQNHEQFCP FANTVCEYCE MELIRDQLAL HCDTDCLKAP
250 260 270 280 290 300
VACTFSTFGC REKMTRNELA QHMQEFTQMH MRYMAEFLRS QTLNNCTMPS AAAHLSSDDR
310 320 330 340 350 360
GASARSPDSC QCKQELLNLR ETVLELEGRL VRQDQQIREL CIHNDTQKNQ VTELRRKLVS
370 380 390 400 410 420
LEESTRELEA QQYQGIYVWR VENFSHHLRN QEAGQPIVLH SPPFYTGRPG YKLCLRLHLQ
430 440 450 460 470 480
TPSAPRCSNF ISLFVHTMQG EFDSQLSWPL QGTIRLAVLD QVEGQHHIEV METKPDLQAF
490 500 510 520 530 540
QRPTVMRNPK GFGYVTFLHL QALRQRGFVK EDVLLVRCEV TPRFDASLRR EGVQPRGPEP
SI