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hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1
Stable Identifier
R-HSA-8948063
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-1 family signaling (Homo sapiens)
Interleukin-1 signaling (Homo sapiens)
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Homo sapiens)
General
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IL1 induces the poly-ubiquitination and degradation of IRAK1. Pellino1-3 possess E3 ligase activity and are believed to directly catalyse polyubiquitylation of IRAK1 (Xiao et al. 2008; Butler et al. 2007; Ordureau et al. 2008). They are capable of catalysing the formation of K63- and K48-linked polyubiquitin chains; the type of linkage is controlled by the collaborating E2 enzyme. All the Pellino proteins can combine with the E2 heterodimer UBE2N:UBE2V1 (Ubc13:Uev1a) to catalyze K63-linked ubiquitylation (Ordureau et al. 2008). IRAK1 polyubiquitination was originally thought to tag IRAK1 for proteolysis by the proteasome, but more recently has been shown to involve K63-linked, not K48-linked polyubiquitination (Windheim et al. 2008; Conze et al. 2008), which is believed to have a scaffoling function. IRAK1 is ubiquitinated on K134 and K180; mutation of these sites impairs IL1R-mediated ubiquitination of IRAK1 (Conze et al. 2008). Some authors have proposed a role for TRAF6 as the E3 ubiquitin ligase that catalyzes polyubiquitination of IRAK1 (Conze et al. 2008) but this view has been refuted (Windheim et al. 2008, Xiao et al. 2008). The current consensus is that Pellino proteins are the physiologically-relevant IRAK1 E3 ubiquitin ligases.
Literature References
PubMed ID
Title
Journal
Year
17997719
The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1
Peggie, M
,
Ordureau, A
,
Carrick, E
,
Morrice, N
,
Windheim, M
,
Smith, H
,
Cohen, P
Biochem J
2008
Participants
Input
hp-IRAK1:p-Pellino, IRAK4:p-Pellino [cytosol]
(Homo sapiens)
x 2
UBE2N:UBE2V1:K63polyUb [cytosol]
(Homo sapiens)
Output
IRAK1:Pellino:E2 complexes [cytosol]
(Homo sapiens)
Participates
as an event of
Interleukin-1 signaling (Homo sapiens)
Orthologous Events
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Caenorhabditis elegans)
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Canis familiaris)
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Drosophila melanogaster)
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Mus musculus)
hp-IRAK1:p-Pellino, IRAK4:p-Pellino bind UBE2N:UBE2V1 (Sus scrofa)
Authored
Ray, KP (2010-05-17)
Reviewed
Pinteaux, E (2010-09-06)
Created
Jupe, S (2016-11-10)
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