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Switch #:
SWTI000291
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation.

Participants:
(1) Ataxin-1 (ATXN1)
(2) Splicing factor U2AF 65 kDa subunit (U2AF2)
(3) 14-3-3 protein zeta/delta (YWHAZ)

Interactions
Interaction #1 ATXN1 - U2AF2

Is mutually exclusive with Interaction #2 ATXN1 - YWHAZ

Interfaces
(1) LIG_ULM_U2AF65_1 motif (770RKRRWS775) in Ataxin-1 (ATXN1)
(2) RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) (399-460) in Splicing factor U2AF 65 kDa subunit (U2AF2)

Interaction Regulation
PTM-dependent Abrogation (Phosphorylation of S775 on Ataxin-1 (ATXN1)) of the Ataxin-1 (ATXN1) LIG_ULM_U2AF65_1 motif - Splicing factor U2AF 65 kDa subunit (U2AF2) RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S775 : RAC-alpha serine/threonine-protein kinase (AKT1), cAMP-dependent protein kinase catalytic subunit alpha (PRKACA).

Additional Information
Affinity : S775: 9.2 µM, pS775: 35.8 µM
Interaction #2 ATXN1 - YWHAZ

Is mutually exclusive with Interaction #1 ATXN1 - U2AF2

Interfaces
(3) LIG_14-3-3_1 motif (772RRWSAP777) in Ataxin-1 (ATXN1)
(4) 14-3-3 protein (3-236) in 14-3-3 protein zeta/delta (YWHAZ)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S775 on Ataxin-1 (ATXN1)) of the Ataxin-1 (ATXN1) LIG_14-3-3_1 motif - 14-3-3 protein zeta/delta (YWHAZ) 14-3-3 protein interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S775 : RAC-alpha serine/threonine-protein kinase (AKT1), cAMP-dependent protein kinase catalytic subunit alpha (PRKACA).

Additional Information
Affinity : S775: N.D. µM, pS775: 0.4 µM
Context
Switch localisation
ELM curated: nucleus, spliceosome complex, cytosol, internal side of plasma membrane
Inferred: nucleoplasm
References

(1) Phosphorylation of S776 and 14-3-3 binding modulate ataxin-1 interaction with splicing factors.
de Chiara et al. PLoS ONE (2009)

See also

Other switches involving participants
14-3-3 protein zeta/delta (YWHAZ) - 11 more (view)
Ataxin-1 (ATXN1) - 1 more (view)

Other switches involving interfaces
14-3-3 protein - 38 more (view)
LIG_14-3-3_1 - 13 more (view)


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