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

72-275 (RZ domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q28DL4

Entry ID Method Resolution Chain Position Source
AF-Q28DL4-F1 Predicted AlphaFoldDB

No variants for Q28DL4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q28DL4

No associated diseases with Q28DL4

9 regional properties for Q28DL4

Type Name Position InterPro Accession
domain Zinc finger, TRAF-type 149 - 194 IPR001293-1
domain Zinc finger, TRAF-type 206 - 263 IPR001293-2
domain Zinc finger, RING-type 72 - 111 IPR001841
domain MATH/TRAF domain 386 - 535 IPR002083
conserved_site Zinc finger, RING-type, conserved site 87 - 96 IPR017907
domain TNF receptor-associated factor 6, C3HC3D-type RING zinc finger 69 - 126 IPR027139
domain TNF receptor-associated factor 6, MATH domain 387 - 536 IPR037309
domain TNF receptor-associated factor 6, zinc finger 2 159 - 185 IPR041310
domain TRAF1-6, MATH domain 409 - 532 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

3 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.
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).

7 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.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
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.
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.
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
Q6IWL4 traf6 TNF receptor-associated factor 6 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MSILNCRPSF DGVDTDDACC GAMASACCVN TKEDGESPSA GSPSGTPQSL VLEDVQGYDV
70 80 90 100 110 120
EFDPPLESKY ECPICLMALR EAVQTPCGHR FCKACILKSI RDAGHKCPVD NESLMENQLF
130 140 150 160 170 180
PDNFAKREIL SLRVKCPSQG CTETMELRHL ERHLVRCDFA GVECSQCQSS FPKYSLQKHK
190 200 210 220 230 240
FEECPRRQIF CENCAVAMAL EDKLNHDQTC PLAYVTCEYC QTNLIREQMP AHYSMDCTMA
250 260 270 280 290 300
PIPCMYYEFG CTEKMQRNDL ARHLQEFTQA HMRMMAQTLR SFSSSVTPTS HMPDISFCDP
310 320 330 340 350 360
SQFEPAPPSV ATVHSTHTPS QNDCTQETRN LRETIEQLEG RLVRQDHQIR ELIAKMETQC
370 380 390 400 410 420
TYVNELKHTI RSLDNRLGEM ESQQCSGIFI WRINNFNSLL KNQEEERPVV IHSQGFYTGK
430 440 450 460 470 480
PGYKLCLRLH LQLPSAQRCA NYISLFVHTM QGEYDSLLPW PLQGTIRLSI LDQSEGVAMQ
490 500 510 520 530 540
DQEEVMDTKP ELLAFQRPTV ARNPKGFGYV TFMHLQALKQ RQYVKNDTLL VRCSVTTHLD
550
LISPRREGFQ PRSGDGAL