NECAP (adaptin-ear-binding coat-associated protein) Plextrin Homology (PH) fold with ear-like function (PHear) domain; NECAPs are alpha-ear-binding proteins that enrich on clathrin-coated vesicles (CCVs). NECAP 1 is expressed in brain and non-neuronal tissues and cells while NECAP 2 is ubiquitously expressed. The PH-like domain of NECAPs is a protein-binding interface that mimics the FxDxF motif binding properties of the alpha-ear and is called PHear (PH fold with ear-like function) domain. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45555767   5 SVLIVKPEVFIYKIPPRASNRGYRAGDWNLKEPTWTGRMRLVAKGTAVVLKLEDKTSGALFANCPIDTYPGVAIEAVSDS 84
Cdd:cd13228   1 SVLLVKPEVYVYRIPPRASAAGYRAADWGLEKPIWTGRLRVVAKGEECEIRLEDPNTGELFAQCPVDVDPGTAVEPVLDS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45555767  85 SRYFVIRVQDDNGRSAFLGLGFGDRSDSFDLNVALQDHFK 124
Cdd:cd13228  81 SRYFVLRVEDGAGRHAFIGIGFRERSDAFDFNVALQDHFK 120

NECAP (adaptin-ear-binding coat-associated protein) Plextrin Homology (PH) fold with ear-like function (PHear) domain; NECAPs are alpha-ear-binding proteins that enrich on clathrin-coated vesicles (CCVs). NECAP 1 is expressed in brain and non-neuronal tissues and cells while NECAP 2 is ubiquitously expressed. The PH-like domain of NECAPs is a protein-binding interface that mimics the FxDxF motif binding properties of the alpha-ear and is called PHear (PH fold with ear-like function) domain. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45555767   5 SVLIVKPEVFIYKIPPRASNRGYRAGDWNLKEPTWTGRMRLVAKGTAVVLKLEDKTSGALFANCPIDTYPGVAIEAVSDS 84
Cdd:cd13228   1 SVLLVKPEVYVYRIPPRASAAGYRAADWGLEKPIWTGRLRVVAKGEECEIRLEDPNTGELFAQCPVDVDPGTAVEPVLDS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45555767  85 SRYFVIRVQDDNGRSAFLGLGFGDRSDSFDLNVALQDHFK 124
Cdd:cd13228  81 SRYFVLRVEDGAGRHAFIGIGFRERSDAFDFNVALQDHFK 120