Switch #: SWTI000605

Switch type: Binary

Switch subtype: Pre-translational

Description:
Alternative splicing removes the AP-2 beta-appendage-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit beta (Ap2b1). With other enzymes (members of the eukaryotic diacylglycerol kinase family, and Synaptojanin-1 (Synj1)), Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) optimises the regional lipid environment necessary for clathrin coat formation. There are three different C-terminal splice variants of Pip5k1c: one (PIPKIgamma687) can bind selectively to Talin-1 (Tln1) via the C-terminal extension (switch details), one (PIPKIgamma661) can bind to both Talin-1 (Tln1) and AP-2 complex subunit beta (Ap2b1), and one (PIPKIgamma635) can bind to neither protein. This flexibility could impart importantly different biological functions to each isoform. For example, in humans PIP5K1C (PIPKIgamma661 in mouse) is proposed to act upstream of Rac/Rho and the differential regulation of PIP5K-gamma and -alpha might allow them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis (See (here)).

Participants:
(1) Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c)
(2) AP-2 complex subunit beta (Ap2b1)

(1) Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor beta2 appendage.
Thieman et al. J. Biol. Chem. (2009)

Other switches involving participants
Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) - 5 more (view)
AP-2 complex subunit beta (Ap2b1) - 1 more (view)

Other switches involving interfaces
Beta2-adaptin appendage, C-terminal sub-domain - 2 more (view)
ELM:TRG_AP2beta_CARGO_2 - 1 more (view)