Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 (also called Ral GEF with PH domain and SH3 binding motif 1;RALGEF2/ Ral guanine nucleotide exchange factor 2; RalA exchange factor RalGPS1; Ral guanine nucleotide exchange factor RalGPS1A2; ras-specific guanine nucleotide-releasing factor RalGPS1) and RalGPS2 (also called Ral GEF with PH domain and SH3 binding motif 2; Ral-A exchange factor RalGPS2; ras-specific guanine nucleotide-releasing factor RalGPS22). They activate small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thereby regulating various downstream cellular processes. Structurally they contain an N-terminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal PH domain. The Cdc25-like catalytic domain interacts with Ral and its PH domain ensures the correct membrane localization. Its PXXP motif is thought to interact with the SH3 domain of Grb2. 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 1720399100 320 TMEGPLRRKTLLKEGRKPALSSWTRYWVVLSGATLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 399
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720399100 400 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSSRPQ 435
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116

Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 (also called Ral GEF with PH domain and SH3 binding motif 1;RALGEF2/ Ral guanine nucleotide exchange factor 2; RalA exchange factor RalGPS1; Ral guanine nucleotide exchange factor RalGPS1A2; ras-specific guanine nucleotide-releasing factor RalGPS1) and RalGPS2 (also called Ral GEF with PH domain and SH3 binding motif 2; Ral-A exchange factor RalGPS2; ras-specific guanine nucleotide-releasing factor RalGPS22). They activate small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thereby regulating various downstream cellular processes. Structurally they contain an N-terminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal PH domain. The Cdc25-like catalytic domain interacts with Ral and its PH domain ensures the correct membrane localization. Its PXXP motif is thought to interact with the SH3 domain of Grb2. 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 1720399100 320 TMEGPLRRKTLLKEGRKPALSSWTRYWVVLSGATLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 399
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720399100 400 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSSRPQ 435
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720399100   1 MSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTRDYIRSLK-MVPSIPYLGIYLLDLIYIDSAYPas 79
Cdd:cd00155    98 MAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGpNPPCVPFLGVYLKDLTFLHEGNP-- 175

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720399100  80 GSIMENEQRSNQMNNILRIIADLQV--SCSYDhLTTLPHVQKYLKSVRYIEELqkfvEDDNYKLSLR 144
Cdd:cd00155   176 DFLEGNLVNFEKRRKIAEILREIRQlqSNSYE-LNRDEDILAFLWKLLELILN----EDELYELSLE 237

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 1720399100  319 PTMEGPLRRKTllkegrKPALSSWTRYWVVLSGATLLYYGAKSlrgtdrKHYKSTPGKKVSIVGWMVQLPDDPEHPD--- 395
Cdd:smart00233   1 VIKEGWLYKKS------GGGKKSWKKRYFVLFNSTLLYYKSKK------DKKSYKPKGSIDLSGCTVREAPDPDSSKkph 68

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720399100  396 IFQLNNPDkGNVYKFQTGSRFHAILWHKHLDDACK 430
Cdd:smart00233  69 CFEIKTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 (also called Ral GEF with PH domain and SH3 binding motif 1;RALGEF2/ Ral guanine nucleotide exchange factor 2; RalA exchange factor RalGPS1; Ral guanine nucleotide exchange factor RalGPS1A2; ras-specific guanine nucleotide-releasing factor RalGPS1) and RalGPS2 (also called Ral GEF with PH domain and SH3 binding motif 2; Ral-A exchange factor RalGPS2; ras-specific guanine nucleotide-releasing factor RalGPS22). They activate small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thereby regulating various downstream cellular processes. Structurally they contain an N-terminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal PH domain. The Cdc25-like catalytic domain interacts with Ral and its PH domain ensures the correct membrane localization. Its PXXP motif is thought to interact with the SH3 domain of Grb2. 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 1720399100 320 TMEGPLRRKTLLKEGRKPALSSWTRYWVVLSGATLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 399
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720399100 400 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSSRPQ 435
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720399100   1 MSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTRDYIRSLK-MVPSIPYLGIYLLDLIYIDSAYPas 79
Cdd:cd00155    98 MAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGpNPPCVPFLGVYLKDLTFLHEGNP-- 175

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720399100  80 GSIMENEQRSNQMNNILRIIADLQV--SCSYDhLTTLPHVQKYLKSVRYIEELqkfvEDDNYKLSLR 144
Cdd:cd00155   176 DFLEGNLVNFEKRRKIAEILREIRQlqSNSYE-LNRDEDILAFLWKLLELILN----EDELYELSLE 237

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 1720399100  319 PTMEGPLRRKTllkegrKPALSSWTRYWVVLSGATLLYYGAKSlrgtdrKHYKSTPGKKVSIVGWMVQLPDDPEHPD--- 395
Cdd:smart00233   1 VIKEGWLYKKS------GGGKKSWKKRYFVLFNSTLLYYKSKK------DKKSYKPKGSIDLSGCTVREAPDPDSSKkph 68

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720399100  396 IFQLNNPDkGNVYKFQTGSRFHAILWHKHLDDACK 430
Cdd:smart00233  69 CFEIKTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology (PH) 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 1720399100 321 MEGPLRRKTllkegrKPALSSWTRYWVVLSGATLLYYgakslrgTDRKHYKSTPGKKVSIVGWM-VQLPDDPEHPDIFQL 399
Cdd:cd00821     1 KEGYLLKRG------GGGLKSWKKRWFVLFEGVLLYY-------KSKKDSSYKPKGSIPLSGILeVEEVSPKERPHCFEL 67

                          90       100
                  ....*....|....*....|....*.
gi 1720399100 400 NNPDkGNVYKFQTGSRFHAILWHKHL 425
Cdd:cd00821    68 VTPD-GRTYYLQADSEEERQEWLKAL 92

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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 1720399100 321 MEGPLRRKTLLKEGRKPALS-SWTRYWVVLSGATLLYYgaKslrgtDRKHYKSTPGKK----VSIVGWMVQLPDD---PE 392
Cdd:cd10571     1 MEGFLERKHEWESGGKKASNrSWKNVYTVLRGQELSFY--K-----DQKAAKSGITYAaeppLNLYNAVCEVASDytkKK 73

                          90       100
                  ....*....|....*....|..
gi 1720399100 393 HpdIFQLNNPDkGNVYKFQTGS 414
Cdd:cd10571    74 H--VFRLKLSD-GAEFLFQAKD 92

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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 1720399100 321 MEGPLRRKTLLKegrkpalSSWTRYWVVLSGATLLYY----------GAKSLRgtdrkhykstpgKKVSIvgwmVQLPDD 390
Cdd:cd13215    23 KSGYLSKRSKRT-------LRYTRYWFVLKGDTLSWYnsstdlyfpaGTIDLR------------YATSI----ELSKSN 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720399100 391 PEHPDIFQLNNPDKgnVYKFQTGSRFHAILWHKHL 425
Cdd:cd13215    80 GEATTSFKIVTNSR--TYKFKADSETSADEWVKAL 112