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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974141089   6 MEGPLFLQSQRFGTKRWRKTWAVLYPASPHGVARLEFFDHKGSSSGGGRGSSRrLDCKVIRLAECVSVAPVTVETPPEPG 85
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSGGKPSKRE-SDRKVIRLSDCVSVAPAGGESSPPRD 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974141089  86 ATAFRLDTAQRSHLLAADAPSSAAWVQTLCRNAF 119
Cdd:cd14676   80 TAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally 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. 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 974141089   6 MEGPLFLQSQRFGTKRWRKTWAVLYPASPHGVARLEFFDHKGSSSGGGRGSSRrLDCKVIRLAECVSVAPVTVETPPEPG 85
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSGGKPSKRE-SDRKVIRLSDCVSVAPAGGESSPPRD 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974141089  86 ATAFRLDTAQRSHLLAADAPSSAAWVQTLCRNAF 119
Cdd:cd14676   80 TAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974141089     5 VMEGPLFLQSQRFGtKRWRKTWAVLYPasphgvARLEFFDHKGSSSGGGRGssrrldcKVIRLAECVSVAPVTVETPPEP 84
Cdd:smart00233   2 IKEGWLYKKSGGGK-KSWKKRYFVLFN------STLLYYKSKKDKKSYKPK-------GSIDLSGCTVREAPDPDSSKKP 67

                           90       100       110
                   ....*....|....*....|....*....|....
gi 974141089    85 GatAFRLDTAQR-SHLLAADAPSSA-AWVQTLCR 116
Cdd:smart00233  68 H--CFEIKTSDRkTLLLQAESEEEReKWVEALRK 99

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally 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. 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 974141089   6 MEGPLFLQSQRFGTKRWRKTWAVLYPASPHGVARLEFFDHKGSSSGGGRGSSRrLDCKVIRLAECVSVAPVTVETPPEPG 85
Cdd:cd14676    1 KEGQLYLQQQKFFGKKWRKFWAVLYPASPCGVARLEFFEGKGGPSGGKPSKRE-SDRKVIRLSDCVSVAPAGGESSPPRD 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 974141089  86 ATAFRLDTAQRSHLLAADAPSSAAWVQTLCRNAF 119
Cdd:cd14676   80 TAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974141089     5 VMEGPLFLQSQRFGtKRWRKTWAVLYPasphgvARLEFFDHKGSSSGGGRGssrrldcKVIRLAECVSVAPVTVETPPEP 84
Cdd:smart00233   2 IKEGWLYKKSGGGK-KSWKKRYFVLFN------STLLYYKSKKDKKSYKPK-------GSIDLSGCTVREAPDPDSSKKP 67

                           90       100       110
                   ....*....|....*....|....*....|....
gi 974141089    85 GatAFRLDTAQR-SHLLAADAPSSA-AWVQTLCR 116
Cdd:smart00233  68 H--CFEIKTSDRkTLLLQAESEEEReKWVEALRK 99