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 595582299    506 VLKGIPESLRGELWLLFSGAW-NEMVTHPGYYAELVEKSLGKYSLATEEIERDLHRSMPEHPAFQ--NELGIAALRRVLT 582
Cdd:smart00164    1 VRKGVPPSLRGVVWKLLLNAQpMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQdkEGPGQESLRRVLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299    583 AYAFRNPTIGYCQAMNIVTSVLLLY-GSEEEAFWLLVALCERMLPDYYNTRVVGALVDQGIFEELTRDVLPRLSEKMQEL 661
Cdd:smart00164   81 AYALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYLPDMSGLQLDLLQLDRLVKEYDPDLYKHLKDL 160

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 595582299    662 GV-ISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKVILQVALAVLDANVEQLL 716
Cdd:smart00164  161 GItPSLYALRWFLTLFARELPLEIVLRIWDVLFAEGSDFLFRVALALLKLHRDVLL 216

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                            10        20
                    ....*....|....*....|....*.
gi 595582299    887 RMFRLLDQNKDSLINFKEFVTGMSGM 912
Cdd:smart00054    4 EAFRLFDKDGDGKIDFEEFKDLLKAL 29

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 595582299    506 VLKGIPESLRGELWLLFSGAW-NEMVTHPGYYAELVEKSLGKYSLATEEIERDLHRSMPEHPAFQ--NELGIAALRRVLT 582
Cdd:smart00164    1 VRKGVPPSLRGVVWKLLLNAQpMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQdkEGPGQESLRRVLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299    583 AYAFRNPTIGYCQAMNIVTSVLLLY-GSEEEAFWLLVALCERMLPDYYNTRVVGALVDQGIFEELTRDVLPRLSEKMQEL 661
Cdd:smart00164   81 AYALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYLPDMSGLQLDLLQLDRLVKEYDPDLYKHLKDL 160

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 595582299    662 GV-ISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKVILQVALAVLDANVEQLL 716
Cdd:smart00164  161 GItPSLYALRWFLTLFARELPLEIVLRIWDVLFAEGSDFLFRVALALLKLHRDVLL 216

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299   554 IERDLHRSMPEHPAFQNELGIAALRRVLTAYAFRNPTIGYCQAMNIVTSVLLL-YGSEEEAFWLLVALCER-MLPDYYNT 631
Cdd:pfam00566   12 IEKDVPRTFPHSFFFDNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENyLLRDFYTP 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299   632 RVVGALVDQGIFEELTRDVLPRLSEKMQELGV-ISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKV-ILQVALAVLD 709
Cdd:pfam00566   92 DFPGLKRDLYVFEELLKKKLPKLYKHLKELGLdPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVALAILK 171

                   ....*..
gi 595582299   710 ANVEQLL 716
Cdd:pfam00566  172 RFREELL 178

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 595582299   143 KMRKQFGMPEGEKLVNYYSCNFWKGRVPRQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEK--NATLLFPESIRVD 220
Cdd:pfam02893    2 LFRKKFKLPPEERLIASYSCYLNRDGGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKlkGGANLFPNGIQVE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 595582299   221 TRDQElFFSMFLNIGETFKLMEQLANLAMRQL 252
Cdd:pfam02893   82 TGSND-KFSFAGFVTRDEAIEFILALLKNAHP 112

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 595582299   291 RATFRLPKDERLDGHTGCTLWTPFnkLHIPGQMFISNNYICFASKEEDA-CRLIIPLREVTIVEK-ADSSSVLPSPLSIS 368
Cdd:pfam02893    4 RKKFKLPPEERLIASYSCYLNRDG--GPVQGRLYLTNYRLCFRSLPKGWsTKVVIPLVDIEEIEKlKGGANLFPNGIQVE 81

                           90       100
                   ....*....|....*....|....*....
gi 595582299   369 TKSKMTFLFANLKDRDFLVQRISDFLQKT 397
Cdd:pfam02893   82 TGSNDKFSFAGFVTRDEAIEFILALLKNA 110

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                            10        20
                    ....*....|....*....|....*.
gi 595582299    887 RMFRLLDQNKDSLINFKEFVTGMSGM 912
Cdd:smart00054    4 EAFRLFDKDGDGKIDFEEFKDLLKAL 29

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.

                           10        20
                   ....*....|....*....|....*.
gi 595582299   887 RMFRLLDQNKDSLINFKEFVTGMSGM 912
Cdd:pfam00036    4 EIFRLFDKDGDGKIDFEEFKELLKKL 29

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 595582299    506 VLKGIPESLRGELWLLFSGAW-NEMVTHPGYYAELVEKSLGKYSLATEEIERDLHRSMPEHPAFQ--NELGIAALRRVLT 582
Cdd:smart00164    1 VRKGVPPSLRGVVWKLLLNAQpMDTSADKDLYSRLLKETAPDDKSIVHQIEKDLRRTFPEHSFFQdkEGPGQESLRRVLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299    583 AYAFRNPTIGYCQAMNIVTSVLLLY-GSEEEAFWLLVALCERMLPDYYNTRVVGALVDQGIFEELTRDVLPRLSEKMQEL 661
Cdd:smart00164   81 AYALYNPEVGYCQGMNFLAAPLLLVmEDEEDAFWCLVKLMERYGPNFYLPDMSGLQLDLLQLDRLVKEYDPDLYKHLKDL 160

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 595582299    662 GV-ISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKVILQVALAVLDANVEQLL 716
Cdd:smart00164  161 GItPSLYALRWFLTLFARELPLEIVLRIWDVLFAEGSDFLFRVALALLKLHRDVLL 216

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299   554 IERDLHRSMPEHPAFQNELGIAALRRVLTAYAFRNPTIGYCQAMNIVTSVLLL-YGSEEEAFWLLVALCER-MLPDYYNT 631
Cdd:pfam00566   12 IEKDVPRTFPHSFFFDNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENyLLRDFYTP 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299   632 RVVGALVDQGIFEELTRDVLPRLSEKMQELGV-ISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKV-ILQVALAVLD 709
Cdd:pfam00566   92 DFPGLKRDLYVFEELLKKKLPKLYKHLKELGLdPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVALAILK 171

                   ....*..
gi 595582299   710 ANVEQLL 716
Cdd:pfam00566  172 RFREELL 178

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 595582299  154 EKLVNYYSCNFWKGRVPRQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEKNATLLFPESIRVDTRDQELFFSMFLN 233
Cdd:cd13217     2 EKLVTYYSCSYWKGRVPRQGWLYLSINHLCFYSFLLGSESKLIIRWTEVSDLERTSNTILTDTIKVNTRSKEHPFSMFLN 81

                          90
                  ....*....|....*...
gi 595582299  234 IGETFKLMEQLANLAMRQ 251
Cdd:cd13217    82 ISETFKLMEQLAQIPDRP 99

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 595582299  154 EKLVNYYSCNFWKGRVPRQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEKNATLLFPESIRVDTRDQELFFSMFLN 233
Cdd:cd13350     2 EKLVTYYSCSYWRGRVPCQGWLYLSTNFLSFYSFLLGSEIKLIISWDEISKLEKTSNVILTESIHVCSRGEDHYFSMFLH 81

                          90
                  ....*....|....*...
gi 595582299  234 IGETFKLMEQLANLAMRQ 251
Cdd:cd13350    82 INETFLLMEQLANYAVRR 99

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 595582299  300 ERLDGHTGCTLWTPFNKLHIPGQMFISNNYICFASKEEDACRLIIPLREVTIVEKADSSSVLPSPLSISTKSKMTFLFAN 379
Cdd:cd13353     2 EKLHEVVDCSLWTPFSRCHTAGRMYTSDSYICFASKEDGSCNVILPLREVVSIEKMEDTSLLPNPIIVSIRSKMAFQFIE 81

                  ....*....
gi 595582299  380 LKDRDFLVQ 388
Cdd:cd13353    82 LKDRDSLVE 90

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 595582299   143 KMRKQFGMPEGEKLVNYYSCNFWKGRVPRQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEK--NATLLFPESIRVD 220
Cdd:pfam02893    2 LFRKKFKLPPEERLIASYSCYLNRDGGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKlkGGANLFPNGIQVE 81

                           90       100       110
                   ....*....|....*....|....*....|..
gi 595582299   221 TRDQElFFSMFLNIGETFKLMEQLANLAMRQL 252
Cdd:pfam02893   82 TGSND-KFSFAGFVTRDEAIEFILALLKNAHP 112

TBC1 domain family member 8B (TBC1D8B) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain, repeat 2; 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 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 595582299  308 CTLWTPFNKLHIPGQMFISNNYICFASKEEDACRLIIPLREVTIVEKADsssVLPSPLSISTKSKMTFLFANLKDRDFLV 387
Cdd:cd13352    10 CFLWVPFSHFNTHGKMCISENYICFASQDGSLCSVIIPLREVLSIDKTD---DSSRAVTISTKGKRAFRFTEVKDFEQLV 86

                  ...
gi 595582299  388 QRI 390
Cdd:cd13352    87 AKL 89

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 595582299   291 RATFRLPKDERLDGHTGCTLWTPFnkLHIPGQMFISNNYICFASKEEDA-CRLIIPLREVTIVEK-ADSSSVLPSPLSIS 368
Cdd:pfam02893    4 RKKFKLPPEERLIASYSCYLNRDG--GPVQGRLYLTNYRLCFRSLPKGWsTKVVIPLVDIEEIEKlKGGANLFPNGIQVE 81

                           90       100
                   ....*....|....*....|....*....
gi 595582299   369 TKSKMTFLFANLKDRDFLVQRISDFLQKT 397
Cdd:pfam02893   82 TGSNDKFSFAGFVTRDEAIEFILALLKNA 110

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 595582299  299 DERLDGHTGCTLWTpfNKLHIPGQMFISNNYICFASKEEDA-CRLIIPLREVTIVEKADSSSVLPSPLSISTKSKMTFLF 377
Cdd:cd10570     1 IEKLGVRFCCALRP--RKLPLEGTLYLSTYRLIFSSKADGDeTKLVIPLVDITDVEKIAGASFLPSGLIITCKDFRTIKF 78

                          90
                  ....*....|....*..
gi 595582299  378 ANLKDrDFLVQRISDFL 394
Cdd:cd10570    79 SFDSE-DEAVKVIARVL 94

GRAM domain-containing protein 4 (GRAMDC4) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; GRAMDC4 is a membrane protein. Nothing is known about its function. Paralogs include: GRAMDC1A, GRAMDC1B, GRAMDC1C, GRAMDC2, GRAMDC3, and GRAMDC-like proteins. It contains a single PH-GRAM domain at its 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 595582299  171 RQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEKNATLLF-PES-----IRVDTRDQELFF 228
Cdd:cd13221    24 RNGRLYLTENYLCFESSSSSSKKNVVIPLTDITRIEKAKPYSFlPGSgmsieVSVSSADKPLFF 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 595582299  153 GEKLVNYYSCNFWKGrVPRQGWLYLTVNHLCFYSFLLGKEVSLVVQWVDVTRLEK 207
Cdd:cd13216     1 TEKLIASYYCYLIRV-LPVYGKLYVSNNYLCFRSLLPGVSTKMILPLRDIENVEK 54

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 595582299  859 RIDASQFRELFASLTPwacgshTPVLAGRMFRLLDQNKDSLINFKEFVTGMSGMYHGD 916
Cdd:COG5126    85 KISADEFRRLLTALGV------SEEEADELFARLDTDGDGKISFEEFVAAVRDYYTPD 136

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 595582299  299 DERLDGHTGCTLwtpFNKLHIPGQMFISNNYICFASKEEDA-CRLIIPLREVTIVEKA 355
Cdd:cd13216     1 TEKLIASYYCYL---IRVLPVYGKLYVSNNYLCFRSLLPGVsTKMILPLRDIENVEKE 55