LIG_TRAF2_1
ELM server details
ELM
blue dot
Functional site class:
 TRAF2 binding site
Functional site description:
 Endogenous TRAF2 is a cytosolic protein that is recruited to membrane associated receptors.
ELM(s): LIG_TRAF2_1, LIG_TRAF2_2
LIG_TRAF2_1 description: Major TRAF2-binding consensus motif. Members of the tumor necrosis factor receptor (TNFR) superfamily initiate intracellular signaling by recruiting the C-domain of the TNFR-associated factors (TRAFs) through their cytoplasmic tails.
Pattern: [PSAT].[QE]E
Present in taxon(s): Eukaryota  
Not represented in taxon(s):

o See instances for LIG_TRAF2_1


o Abstract

The cell activation, cell survival, and antiapoptotic functions of the tumor necrosis factor (TNF) receptor superfamily are mostly mediated by the family of the TNF receptor-associated factors (TRAF1-6). The TRAF proteins are found in mammals, drosophila, C.elegans, and Dictyostelium discoideum. Most of the biological effects are mediated by the activation of the transcriptional factor NF-kB and Ap-1 family, which can turn on numerous genes involved in various aspects of cellular and immune functions.
TRAF2 was isolated biochemically from the TNFR-2 signaling complex and is the prototype of the six TRAF family members. Beside TNFR-2, a number of other TNFRs such as CD30, CD40, CD27, Ox40, 4-1BB, and ATAR also recruit TRAF2. In addition, the transforming effect of the Epstein-Barr virus (EBV) oncoprotein latent infection membrane protein-1 (LMP1) is partly TRAF2 mediated. Several linear consensus sequences have been proposed to bind to TRAF2, including PXQX[TSD] motif in LMP1, CD30, CD40, and CD27; the phiSXEE ( phi = large hydrophobic) sequence in TNFR-2 and CD30; and the QEE motif in 4-1BB and Ox40 receptors.
Despite the apparent sequence diversity, the receptor peptides bind to a common site on the surface of the TRAF domain of TRAF2. Crystal structures of the human TRAF2 domain in complex with peptides from the TNFR family members revealed a conserved binding mode and allowed to identify two consensus sequences.

o Selected references

Bradley JR, Pober JS
Tumor necrosis factor receptor-associated factors (TRAFs).
Oncogene 2001 Oct 1;20(44) : 6482-91.
PMID: 11607847

Park YC, Burkitt V, Villa AR, Tong L, Wu H
Structural basis for self-association and receptor recognition of human TRAF2.
Nature 1999 Apr 8;398(6727) : 533-8.
PMID: 10206649

Ye H, Park YC, Kreishman M, Kieff E, Wu H
The structural basis for the recognition of diverse receptor sequences by TRAF2.
Mol Cell 1999 Sep;4(3) : 321-30.
PMID: 10518213

o This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
  signal transduction
Cellular Component
  cytosol
Molecular Function
  signal transducer

 

o Instances for LIG_TRAF2_1

SequencePositionSubsequence
(Click for evidence information)		PDBGene NameProtein DescriptionOrganism
TNR4_HUMAN 262-265 GSFRTPIQEEQADAH - Name=TNFRSF4; Synonyms=TXGP1L; Tumor necrosis factor receptor superfamily member 4 precursor (OX40L receptor) (ACT35 antigen) (TAX transcriptionally-activated glycoprotein 1 receptor) (CD134 antigen). Homo sapiens (Human).
TNR3_HUMAN 402-405 PGLSTPHQEDGKAWH - Name=LTBR; Synonyms=D12S370, TNFCR, TNFRSF3; Tumor necrosis factor receptor superfamily member 3 precursor (Lymphotoxin-beta receptor) (Tumor necrosis factor receptor 2-related protein) (Tumor necrosis factor C receptor). Homo sapiens (Human).
CD27_HUMAN 246-249 EGSTIPIQEDYRKPE - Name=CD27; Synonyms=TNFRSF7; CD27 antigen precursor (CD27L receptor) (T-cell activation antigen CD27) (T14) (Tumor necrosis factor receptor superfamily member 7). Homo sapiens (Human).
TNR8_HUMAN 561-564 HTPHYPEQETEPPLG - Name=TNFRSF8; Synonyms=CD30, D1S166E; Tumor necrosis factor receptor superfamily member 8 precursor (CD30L receptor) (Lymphocyte activation antigen CD30) (KI-1 antigen). Homo sapiens (Human).
TNR8_HUMAN 578-581 SDVMLSVEEEGKEDP - Name=TNFRSF8; Synonyms=CD30, D1S166E; Tumor necrosis factor receptor superfamily member 8 precursor (CD30L receptor) (Lymphocyte activation antigen CD30) (KI-1 antigen). Homo sapiens (Human).
TNR14_HUMAN 175-178 FSPNGTLEECQHQTK - Name=TNFRSF14; Synonyms=HVEA, HVEM; ORFNames=UNQ329/PRO509; Tumor necrosis factor receptor superfamily member 14 precursor (Herpesvirus entry mediator A) (Tumor necrosis factor receptor-like 2) (TR2). Homo sapiens (Human).
TNR14_HUMAN 268-271 DVTTVAVEETIPSFT - Name=TNFRSF14; Synonyms=HVEA, HVEM; ORFNames=UNQ329/PRO509; Tumor necrosis factor receptor superfamily member 14 precursor (Herpesvirus entry mediator A) (Tumor necrosis factor receptor-like 2) (TR2). Homo sapiens (Human).
TNR1B_HUMAN 129-132 WYCALSKQEGCRLCA - Name=TNFRSF1B; Synonyms=TNFBR, TNFR2; Tumor necrosis factor receptor superfamily member 1B precursor (Tumor necrosis factor receptor 2) (TNF-R2) (Tumor necrosis factor receptor type II) (p75) (p80 TNF-alpha receptor) (CD120b antigen) (Etanercept) [Contains: Tumor necrosis factor receptor superfamily member 1b, membrane form; Tumor necrosis factor-binding protein 2 (TBPII) (TBP- 2)]. Homo sapiens (Human).
TNR1B_HUMAN 424-427 EQVPFSKEECAFRSQ - Name=TNFRSF1B; Synonyms=TNFBR, TNFR2; Tumor necrosis factor receptor superfamily member 1B precursor (Tumor necrosis factor receptor 2) (TNF-R2) (Tumor necrosis factor receptor type II) (p75) (p80 TNF-alpha receptor) (CD120b antigen) (Etanercept) [Contains: Tumor necrosis factor receptor superfamily member 1b, membrane form; Tumor necrosis factor-binding protein 2 (TBPII) (TBP- 2)]. Homo sapiens (Human).
TNR5_HUMAN 104-107 TDTICTCEEGWHCTS 1QSC
 Name=CD40; Synonyms=TNFRSF5; Tumor necrosis factor receptor superfamily member 5 precursor (CD40L receptor) (B-cell surface antigen CD40) (CDw40) (Bp50). Homo sapiens (Human).
TNR5_HUMAN 250-253 SNTAAPVQETLHGCQ - Name=CD40; Synonyms=TNFRSF5; Tumor necrosis factor receptor superfamily member 5 precursor (CD40L receptor) (B-cell surface antigen CD40) (CDw40) (Bp50). Homo sapiens (Human).
TNR9_HUMAN 234-237 MRPVQTTQEEDGCSC - Name=TNFRSF9; Synonyms=CD137, ILA; Tumor necrosis factor receptor superfamily member 9 precursor (4-1BB ligand receptor) (T-cell antigen 4-1BB homolog) (T-cell antigen ILA) (CD137 antigen) (CDw137). Homo sapiens (Human).
TNR9_HUMAN 246-249 CSCRFPEEEEGGCEL - Name=TNFRSF9; Synonyms=CD137, ILA; Tumor necrosis factor receptor superfamily member 9 precursor (4-1BB ligand receptor) (T-cell antigen 4-1BB homolog) (T-cell antigen ILA) (CD137 antigen) (CDw137). Homo sapiens (Human).