Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

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                  ....*....|....*....|....*....|..
gi 1950281162  20 VLFQVKECYVYMIPPRKSAASYKADEWDINKW 51
Cdd:cd13228     2 VLLVKPEVYVYRIPPRASAAGYRAADWGLEKP 33

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
                  ....*....|....*....|....*....|..
gi 1950281162  20 VLFQVKECYVYMIPPRKSAASYKADEWDINKW 51
Cdd:cd13228     2 VLLVKPEVYVYRIPPRASAAGYRAADWGLEKP 33

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
                  ....*....|....*....|....*....|..
gi 1950281162  20 VLFQVKECYVYMIPPRKSAASYKADEWDINKW 51
Cdd:cd13228     2 VLLVKPEVYVYRIPPRASAAGYRAADWGLEKP 33