The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
Actinfilin-binding degron
Functional site description:
Actinfilin (Q6TDP4),an actin binding protein, functions as a substrate adaptor for Cul3 (Q13618) dependent E3 ubiquitin ligase for the degradation of proteins involved in neuronal transmission. The Kelch domain (PF01344) of Actinfilin E3 ligase interacts with a hydrophobic motif in kainate receptor GluR6 (Q13002) and the dis-regulation of GluR6 expression can cause cerebral ischemia, stroke and epileptic seizures.
ELM Description:
Actinfilin (Q6TDP4) acts as a substrate adaptor linking substrates to the E3 ubiquitin-ligase complex for degradation. The Kelch domain (PF01344) of actinfilin interacts with a hydrophobic motif in Kainate receptors such as GluR6 (Q13002). The motif is conserved in Mammalia.
Pattern: [AP]P[MV][IM]V
Pattern Probability: 0.0000021
Present in taxon: Mammalia
Interaction Domain:
Kelch_1 (PF01344) Kelch motif (Stochiometry: 1 : 1)
o See 1 Instance for DEG_Kelch_actinfilin_1
o Abstract
Regulation of certain glutamate receptors, scaffolds and signaling proteins are mediated by their proper degradation by kelch domain (PF01344) containing proteins. Actinfilin (Q6TDP4) is a kelch domain containing protein largely enriched in brain especially in cerebrum and cerebellum and is present in postsynaptic density. It plays a key role in actin polymerization, stability, subcellular anchoring and in actin-based neuronal function (Chen,2002). The actinfilin protein contains two functional domains that mediate protein degradation, a BTB domain (PF00651) that binds Cul3-based ligases, and a Kelch domain that interacts with the substrate. The kainate receptor GluR6 (Q13002) binds to the kelch domain of actinfilin through a hydrophobic motif and this interaction is important for the correct regulation of GluR6 surface expression (Salinas,2006).
o 3 selected references:

o 10 GO-Terms:

o 1 Instance for DEG_Kelch_actinfilin_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P42260 Grik2
881 885 RLKHKPQAPVIVKTEEVINM TP 4 Rattus norvegicus (Norway rat)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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