Pathways & interactions
ASAP, PH domain (IPR037844)
Short name: PH_ASAP
Overlapping homologous superfamilies
- PH-like domain superfamily (IPR011993)
- Pleckstrin homology domain (IPR001849)
- ASAP, PH domain (IPR037844)
This entry represents the PH domain of Arf-GAP with SH3 domain, ANK repeat and PH domain-containing proteins (ASAPs). ASAPs (ASAP1, ASAP2, and ASAP3) function as Arf-specific GTPase-activating proteins (GAPs), participate in rhodopsin trafficking, are associated with tumour cell metastasis, modulate phagocytosis, promote cell proliferation, facilitate vesicle budding, Golgi exocytosis, and regulate vesicle coat assembly via a Bin/Amphiphysin/Rvs domain [PMID: 10725410, PMID: 21775626, PMID: 18400762]. Each member has a BAR, PH, Arf GAP, Ank repeat and proline rich domains. ASAP1 and ASAP2 also have a SH3 domain at the C terminus [PMID: 18675341]. The ASAP family is named for the first identified member, ASAP1 [PMID: 9819391].
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 [PMID: 22728242]. 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 [PMID: 15493994]. 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 [PMID: 14594214]. 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 [PMID: 22728242].
- cd13251 (PH_ASAP)