Switches.ELM

Switch #:

SWTI000615

Switch type:
Binary

Description:
Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). NCK2-beta has a clear preference for splice variant 2 (with the YQYI motif) over splice variant 3 (with the YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).

Participants:
(1) Disabled homolog 1 (Dab1)
(2) Cytoplasmic protein NCK2 (NCK2)

Interactions

Interaction #1 Dab1 - NCK2

Interfaces
(1) ELM:LIG_SH2_IA motif (₂₂₀YQVP₂₂₃) in Disabled homolog 1 (Dab1)
(2) SH2 domain_(285-323) in Cytoplasmic protein NCK2 (NCK2)

Interaction Regulation
Alternative splicing Abrogation (Phosphorylation of Y₂₂₀ on Disabled homolog 1 (Dab1)) of the Disabled homolog 1 (Dab1) LIG_SH2_IA motif - Cytoplasmic protein NCK2 (NCK2) SH2 domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: Y₂₂₀: Neuronal proto-oncogene tyrosine-protein kinase Src (Src)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y₂₂₀ : Tyrosine-protein kinase ABL1 (ABL1), Neuronal proto-oncogene tyrosine-protein kinase Src (Src), Proto-oncogene tyrosine-protein kinase Src (SRC).

References

(1) Splice-mediated motif switching regulates Disabled-1 phosphorylation and SH2 domain interactions.
Gao et al. (2012)

(2) Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1.
Keshvara et al. J. Biol. Chem. (2001)