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  Domain Name: PHsplit_syntrophin
Syntrophin Split Pleckstrin homology (PH) domain. Syntrophins are scaffold proteins that associate with associate with the Duchenne muscular dystrophy protein dystrophin and the dystrophin-related proteins, utrophin and dystrobrevin to form the dystrophin glycoprotein complex (DGC). There are 5 members: alpha, beta1, beta2, gamma1, and gamma2) all of which contains a split (also called joined) PH domain and a PDZ domain (PHN-PDZ-PHC). The split PH domain of alpha-syntrophin adopts a canonical PH domain fold and together with PDZ forms a supramodule functioning synergistically in binding to inositol phospholipids. The alpha-syntrophin PH-PDZ supramodule showed strong binding to phosphoinositides PI(3,5)P2 and PI(5)P, modest binding to PI(3,4)P2 and PI(4,5)P2, and weak binding to PI(3)P, PI(4)P, and PI(3,4,5)P. There are a large number of signaling proteins that bind to the PDZ domain of syntrophins: nitric oxide synthase (nNOS), aquaporin-4, voltage-gated sodium channels, potassium channels, serine/threonine protein kinases, and the ATP-binding cassette transporter A1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 2
Total Disease Mutations Found: 1
This domain occurred 5 times on human genes (10 proteins).


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Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  

Feature Name:Total Found:
phosphoinositide binding

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Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

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