TBC1 domain family member 8B (TBC1D8B) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 1; TBC1D8B may act as a GTPase-activating protein for Rab family protein(s). TBC1D8B contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 156 KEKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNVILTESIHVCSQGENHYFSMFL 235
Cdd:cd13350   1 QEKLVTYYSCSYWRGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEISKLEKTSNVILTESIHVCSRGEDHYFSMFL 80

                        90
                ....*....|....*....
gi 38570103 236 HINQTYLLMEQLANYAIRR 254
Cdd:cd13350  81 HINETFLLMEQLANYAVRR 99

Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs; Widespread domain present in Gyp6 and Gyp7, thereby giving rise to the notion that it performs a GTP-activator activity on Rab-like GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103    486 RGIPETLRGELWMLFSGA-VNDMATNPDYYTEVVEQSLGTCNLATEEIERDLRRSLPEHPAFQSDTG--ISALRRVLTAY 562
Cdd:smart00164   3 KGVPPSLRGVVWKLLLNAqPMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQDKEGpgQESLRRVLKAY 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 38570103    563 AYRNPKIGYCQAMNILTSVLLLY-AKEEEAFWLLVAVCERMLPDYFN 608
Cdd:smart00164  83 ALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYL 129

TBC1 domain family member 8B (TBC1D8B) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 1; TBC1D8B may act as a GTPase-activating protein for Rab family protein(s). TBC1D8B contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 156 KEKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNVILTESIHVCSQGENHYFSMFL 235
Cdd:cd13350   1 QEKLVTYYSCSYWRGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEISKLEKTSNVILTESIHVCSRGEDHYFSMFL 80

                        90
                ....*....|....*....
gi 38570103 236 HINQTYLLMEQLANYAIRR 254
Cdd:cd13350  81 HINETFLLMEQLANYAVRR 99

Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs; Widespread domain present in Gyp6 and Gyp7, thereby giving rise to the notion that it performs a GTP-activator activity on Rab-like GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103    486 RGIPETLRGELWMLFSGA-VNDMATNPDYYTEVVEQSLGTCNLATEEIERDLRRSLPEHPAFQSDTG--ISALRRVLTAY 562
Cdd:smart00164   3 KGVPPSLRGVVWKLLLNAqPMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQDKEGpgQESLRRVLKAY 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 38570103    563 AYRNPKIGYCQAMNILTSVLLLY-AKEEEAFWLLVAVCERMLPDYFN 608
Cdd:smart00164  83 ALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYL 129

Rab-GTPase-TBC domain; Identification of a TBC domain in GYP6_YEAST and GYP7_YEAST, which are GTPase activator proteins of yeast Ypt6 and Ypt7, implies that these domains are GTPase activator proteins of Rab-like small GTPases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38570103   532 IERDLRRSLPEHPAFQSDTGISALRRVLTAYAYRNPKIGYCQAMNILTSVLLL-YAKEEEAFWLLVAVCER-MLPDYF 607
Cdd:pfam00566  12 IEKDVPRTFPHSFFFDNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENyLLRDFY 89

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38570103    152 GLPEKEKLVTYYSCSYWKgRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTS 212
Cdd:smart00568   1 KLPEEEKLIADYSCYLSR-TGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38570103    292 RLPKGESLKEVHECFLW--VPFshfntHGKMCISENYICFASQD-GNQCSVIIPLREVLAIDK 351
Cdd:smart00568   1 KLPEEEKLIADYSCYLSrtGPV-----QGRLYISNYRLCFRSNLpGKLTKVVIPLADITRIEK 58

TBC1 domain family member 8B (TBC1D8B) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 1; TBC1D8B may act as a GTPase-activating protein for Rab family protein(s). TBC1D8B contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 156 KEKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNVILTESIHVCSQGENHYFSMFL 235
Cdd:cd13350   1 QEKLVTYYSCSYWRGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEISKLEKTSNVILTESIHVCSRGEDHYFSMFL 80

                        90
                ....*....|....*....
gi 38570103 236 HINQTYLLMEQLANYAIRR 254
Cdd:cd13350  81 HINETFLLMEQLANYAVRR 99

TCB1D8 and TCB1D9 family Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 1; TBC1D8, TBC1D8B, TBC1D9 and TBC1D9B may act as a GTPase-activating proteins for Rab family protein(s). They all contain an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 157 EKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNVILTESIHVCSQGENHYFSMFLH 236
Cdd:cd13217   2 EKLVTYYSCSYWKGRVPRQGWLYLSINHLCFYSFLLGSESKLIIRWTEVSDLERTSNTILTDTIKVNTRSKEHPFSMFLN 81

                        90
                ....*....|....*...
gi 38570103 237 INQTYLLMEQLANYAIRR 254
Cdd:cd13217  82 ISETFKLMEQLAQIPDRP 99

TCB1D8 and TCB1D9 family Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 2; TBC1D8, TBC1D8B, TBC1D9 and TBC1D9B may act as a GTPase-activating proteins for Rab family protein(s). They all contain an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 297 ESLKEVHECFLWVPFSHFNTHGKMCISENYICFASQDGNQCSVIIPLREVLAIDKTNDSS---KSVIISIKGKTAFRFHE 373
Cdd:cd13218   2 EKLKEVHDCFLWTPFSHFHTHGKMFISENYICFASKEGNLCSVIIPLREVLAIEKTNDSSvlpKPVIISIKGKMAFRFSE 81

                        90
                ....*....|....*
gi 38570103 374 VKDFEQLVAKLRLRC 388
Cdd:cd13218  82 LKDRDELVAKLRLKL 96

Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs; Widespread domain present in Gyp6 and Gyp7, thereby giving rise to the notion that it performs a GTP-activator activity on Rab-like GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103    486 RGIPETLRGELWMLFSGA-VNDMATNPDYYTEVVEQSLGTCNLATEEIERDLRRSLPEHPAFQSDTG--ISALRRVLTAY 562
Cdd:smart00164   3 KGVPPSLRGVVWKLLLNAqPMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQDKEGpgQESLRRVLKAY 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 38570103    563 AYRNPKIGYCQAMNILTSVLLLY-AKEEEAFWLLVAVCERMLPDYFN 608
Cdd:smart00164  83 ALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYL 129

TBC1 domain family member 8 (TBC1D8; also called Vascular Rab-GAP/TBC-containing protein) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 2; TBC1D8 may act as a GTPase-activating protein for Rab family protein(s). TBC1D8 contains two N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 297 ESLKEVHECFLWVPFSHFNTHGKMCISENYICFASQDGNQCSVIIPLREVLAIDKTNDSS---KSVIISIKGKTAFRFHE 373
Cdd:cd13353   2 EKLHEVVDCSLWTPFSRCHTAGRMYTSDSYICFASKEDGSCNVILPLREVVSIEKMEDTSllpNPIIVSIRSKMAFQFIE 81

                        90
                ....*....|....
gi 38570103 374 VKDFEQLVAKLRLR 387
Cdd:cd13353  82 LKDRDSLVESLLAR 95

GRAM domain-containing protein (GRAMDC) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; The GRAMDC proteins are membrane proteins. Nothing is known about its function. Members include: GRAMDC1A, GRAMDC1B, GRAMDC1C, GRAMDC2, GRAMDC3, GRAMDC4, and GRAMDC-like proteins. All of the members, except for GRAMDC4 are included in this hierarchy. Each contains a single PH-GRAM domain at their N-terminus. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 157 EKLVTYYSCSyWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNV-ILTESIHVCSQGENHYFSMFL 235
Cdd:cd13220   3 ERLIDDFSCA-LQRDILLQGRLYISENHLCFYSNIFGWETKLVIPFKDITSIEKKKTAlIFPNAIEITTKGEKYFFTSFL 81

                        90
                ....*....|..
gi 38570103 236 HINQTYLLMEQL 247
Cdd:cd13220  82 SRDSAYKLLTRV 93

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103   146 KFEKCFGLPEKEKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSN--VILTESIHVC 223
Cdd:pfam02893   2 LFRKKFKLPPEERLIASYSCYLNRDGGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKLKGgaNLFPNGIQVE 81

                          90       100
                  ....*....|....*....|....*...
gi 38570103   224 SqGENHYFSMFLHINQTYLLMEQLANYA 251
Cdd:pfam02893  82 T-GSNDKFSFAGFVTRDEAIEFILALLK 108

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103   287 FNAFFRLPKGESLKEVHECFLWVPFSHfnTHGKMCISENYICFASQ-DGNQCSVIIPLREVLAIDKTNDSS----KSVII 361
Cdd:pfam02893   3 FRKKFKLPPEERLIASYSCYLNRDGGP--VQGRLYLTNYRLCFRSLpKGWSTKVVIPLVDIEEIEKLKGGAnlfpNGIQV 80

                          90
                  ....*....|
gi 38570103   362 SIKGKTAFRF 371
Cdd:pfam02893  81 ETGSNDKFSF 90

Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 38570103 157 EKLVTYYSCSYWKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEK 210
Cdd:cd10570   2 EKLGVRFCCALRPRKLPLEGTLYLSTYRLIFSSKADGDETKLVIPLVDITDVEK 55

C2 and GRAM domain-containing protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; C2GRAM contains two N-terminal C2 domains followed by a single PH-GRAM domain. Since it contains both of these domains it is assumed that this gene cross-links both calcium and phosphoinositide signaling pathways. In general he C2 domain is involved in binding phospholipids in a calcium dependent manner or calcium independent manner. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38570103 157 EKLVTYYSCSYwKGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEVSKLEKTSNVILTESI 220
Cdd:cd13219   2 EFLINDFSCAL-KRKFLYQGRMFLSARHIGFHSNVFGKKTKFVFLWEDIEEIQESPHSLINPAI 64

TBC1 domain family members 9 and 9B (TBC1D9 and TBC1D9B) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 2; TBC1D9 and TCB1D9B may act as a GTPase-activating proteins for Rab family protein(s). TBC1D9 and TCB1D9B contain two N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This cd contains the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570103 157 EKLVTYYSCSYW----KGRVPcqGWLYLSTNFLSFYSFLLgSEIKLIISWDEVSKLEK--TSNVILTESIHVCSQGENHY 230
Cdd:cd13354   2 EKLDGSTDCTLWtpynKRHVW--GTLYLSQNYICFTSKVR-DLVSLVIPLREVTSVEKadSSSVSLPNGILITTKSKMTF 78

                ....*..
gi 38570103 231 fsMFLHI 237
Cdd:cd13354  79 --LFAQI 83

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 2; 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38570103 316 THGKMCISENYICFAS-QDGNQCSVIIPLREVLAIDK---TNDSSKSVIISIKGktafrfHEVKDFEQLVAKLRLRC 388
Cdd:cd13216  18 VYGKLYVSNNYLCFRSlLPGVSTKMILPLRDIENVEKekgFRFGYSGLVIVIKG------HEELFFEFSSKSSRDDC 88