FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 279 PEWLDSDSCQKCDQPFFWNFKQMWDSRKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd15718     1 PEWAESDNCQKCSRPFFWNFKQMWEKKTLGVRQHHCRKCGKAVCDKCSSNRSTIPVMGFEFPVRVCNECY 70

FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 279 PEWLDSDSCQKCDQPFFWNFKQMWDSRKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd15718     1 PEWAESDNCQKCSRPFFWNFKQMWEKKTLGVRQHHCRKCGKAVCDKCSSNRSTIPVMGFEFPVRVCNECY 70

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  16 LLQRVEGSQDVVNMAVIVPKEEGVISVSEDRTVRVW-------LKRDSGQYwPSVYHVMPSPCScmsfnpetRRLSIGLD 88
Cdd:cd00200     1 LRRTLKGHTGGVTCVAFSPDGKLLATGSGDGTIKVWdletgelLRTLKGHT-GPVRDVAASADG--------TYLASGSS 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  89 NGTISEFilseDYNKMTPMKNYQAHQSRVTMILFVLELEWVLSTGQDKQFAWHCSESGQRLGGYR--TSAVASgLQFDVE 166
Cdd:cd00200    72 DKTIRLW----DLETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNS-VAFSPD 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 167 TRHVFIGDHSGQVTILKLEQENCtlVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIggRKGTAI-ELQGHNDKI 245
Cdd:cd00200   147 GTFVASSSQDGTIKLWDLRTGKC--VATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDL--STGKCLgTLRGHENGV 222

                         250       260
                  ....*....|....*....|....*..
gi 1910924708 246 QALSYAQHTRQLISCGSDGGIVIWNMD 272
Cdd:cd00200   223 NSVAFSPDGYLLASGSEDGTIRVWDLR 249

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1910924708 279 PEWL---DSDSCQKCDQPFFWNFkqmwdsrkislRQHHCRKCGKAVCGKCSSKR-SSIPLMGFEFEVRVCDSCHEAIT 352
Cdd:pfam01363   1 PVWVpdsSATVCMICSKPFTFFR-----------RRHHCRNCGRVFCSACSSKKiSLLPELGSNKPVRVCDACYDTLQ 67

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1910924708 190 TLVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWD 227
Cdd:pfam00400   2 KLLKTLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39

coronin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 177 GQVTILKLE-QENCTLVTTFRGHTGGVTALCWDPV-QRVLFSGSSDHSVIMWDIGGRKGTAIE-------LQGHNDKIQA 247
Cdd:PTZ00420   51 GLIGAIRLEnQMRKPPVIKLKGHTSSILDLQFNPCfSEILASGSEDLTIRVWEIPHNDESVKEikdpqciLKGHKKKISI 130

                          90       100       110
                  ....*....|....*....|....*....|
gi 1910924708 248 LSYAQHTRQLI-SCGSDGGIVIWNMDVERQ 276
Cdd:PTZ00420  131 IDWNPMNYYIMcSSGFDSFVNIWDIENEKR 160

FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 279 PEWLDSDSCQKCDQPFFWNFKQMWDSRKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd15718     1 PEWAESDNCQKCSRPFFWNFKQMWEKKTLGVRQHHCRKCGKAVCDKCSSNRSTIPVMGFEFPVRVCNECY 70

FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. WDFY2 contains WD40 motifs and a FYVE domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 279 PEWLDSDSCQKCDQPFFWNFKQMWDSRKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd15757     1 PEWLDSDSCQKCDQPFFWNFKQMWDSKKIGLRQHHCRKCGKAVCGKCSSKRSTIPLMGFEFEVRVCDSCH 70

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  16 LLQRVEGSQDVVNMAVIVPKEEGVISVSEDRTVRVW-------LKRDSGQYwPSVYHVMPSPCScmsfnpetRRLSIGLD 88
Cdd:cd00200     1 LRRTLKGHTGGVTCVAFSPDGKLLATGSGDGTIKVWdletgelLRTLKGHT-GPVRDVAASADG--------TYLASGSS 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  89 NGTISEFilseDYNKMTPMKNYQAHQSRVTMILFVLELEWVLSTGQDKQFAWHCSESGQRLGGYR--TSAVASgLQFDVE 166
Cdd:cd00200    72 DKTIRLW----DLETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNS-VAFSPD 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 167 TRHVFIGDHSGQVTILKLEQENCtlVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIggRKGTAI-ELQGHNDKI 245
Cdd:cd00200   147 GTFVASSSQDGTIKLWDLRTGKC--VATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDL--STGKCLgTLRGHENGV 222

                         250       260
                  ....*....|....*....|....*..
gi 1910924708 246 QALSYAQHTRQLISCGSDGGIVIWNMD 272
Cdd:cd00200   223 NSVAFSPDGYLLASGSEDGTIRVWDLR 249

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  68 PSPCSCMSFNPETRRLSIGLDNGTISEFilseDYNKMTPMKNYQAHQSRVTMILFVLELEWVLSTGQDKQ---FAWHCSE 144
Cdd:cd00200     9 TGGVTCVAFSPDGKLLATGSGDGTIKVW----DLETGELLRTLKGHTGPVRDVAASADGTYLASGSSDKTirlWDLETGE 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 145 SGQRLGGYrTSAVASgLQFDVETRHVFIGDHSGQVTILKLEQENCtlVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVI 224
Cdd:cd00200    85 CVRTLTGH-TSYVSS-VAFSPDGRILSSSSRDKTIKVWDVETGKC--LTTLRGHTDWVNSVAFSPDGTFVASSSQDGTIK 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1910924708 225 MWDIGGRKGTAiELQGHNDKIQALSYAQHTRQLISCGSDGGIVIWNMDVERQ 276
Cdd:cd00200   161 LWDLRTGKCVA-TLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDLSTGKC 211

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1910924708  279 PEWLD---SDSCQKCDQPFFWNfkqmwdsrkisLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCHE 349
Cdd:smart00064   2 PHWIPdeeVSNCMGCGKEFNLT-----------KRRHHCRNCGRIFCSKCSSKKAPLPKLGIERPVRVCDDCYE 64

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1910924708 279 PEWL---DSDSCQKCDQPFFWNFkqmwdsrkislRQHHCRKCGKAVCGKCSSKR-SSIPLMGFEFEVRVCDSCHEAIT 352
Cdd:pfam01363   1 PVWVpdsSATVCMICSKPFTFFR-----------RRHHCRNCGRVFCSACSSKKiSLLPELGSNKPVRVCDACYDTLQ 67

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  11 TRKPILLQRVEGSQDVVNMAVIVPKEEGVISVSEDRTVRVWlKRDSGQYwPSVYHVMPSPCSCMSFNPETRRLSIGLDNG 90
Cdd:cd00200    80 LETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVW-DVETGKC-LTTLRGHTDWVNSVAFSPDGTFVASSSQDG 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708  91 TISEFilseDYNKMTPMKNYQAHQSRVTMILFVLELEWVLSTGQDKQ-FAWHCSeSGQRLGGYR--TSAVASgLQFDVET 167
Cdd:cd00200   158 TIKLW----DLRTGKCVATLTGHTGEVNSVAFSPDGEKLLSSSSDGTiKLWDLS-TGKCLGTLRghENGVNS-VAFSPDG 231

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1910924708 168 RHVFIGDHSGQVTILKLEQENCtlVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWD 227
Cdd:cd00200   232 YLLASGSEDGTIRVWDLRTGEC--VQTLSGHTNSVTSLAWSPDGKRLASGSADGTIRIWD 289

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1910924708 286 SCQKCDQPFFWnfkqmwdsrkiSLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd00065     1 RCMLCGKKFSL-----------FRRRHHCRRCGRVFCSKCSSKKLPLPSFGSGKPVRVCDSCY 52

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1910924708 279 PEWLDSDSCQKCDQPFfwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRssIPLMGFEFE--VRVCDSC 347
Cdd:cd15728     2 PPWADGDYCYECGVKF-----------GITTRKHHCRHCGRLLCSKCSTKE--VPIIKFDLNkpVRVCDVC 59

FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; Lst2, also termed zinc finger FYVE domain-containing protein 28, is a monoubiquitinylated phosphoprotein that functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling. Unlike other FYVE domain-containing proteins, Lst2 displays primarily non-endosomal localization. Its endosomal localization is regulated by monoubiquitinylation. Lst2 physically binds Trim3, also known as BERP or RNF22, which is a coordinator of endosomal trafficking and interacts with Hrs and a complex that biases cargo recycling.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1910924708 279 PEWL---DSDSCQKCDQPFfwnfkqmWDSRkislRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSC 347
Cdd:cd15731     3 PLWVpdeACPQCMACSAPF-------TVLR----RRHHCRNCGKIFCSRCSSNSVPLPRYGQMKPVRVCNHC 63

FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar proteins; ZFYV1, also termed double FYVE-containing protein 1 (DFCP1), or SR3, or tandem FYVE fingers-1, is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYV1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by wortmannin, a PI3-kinase inhibitor. In addition to C-terminal tandem FYVE domain, ZFYV1 contains an N-terminal putative C2H2 type zinc finger and a possible nucleotide binding P-loop.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1910924708 283 DSD--SCQKCDQPFfwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSC 347
Cdd:cd15734     5 DSEikECSVCKRPF-----------SPRLSKHHCRACGQGVCDDCSKNRRPVPSRGWDHPVRVCDPC 60

FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE domain-containing protein 16 (ZFY16), or endosome-associated FYVE domain protein, is a FYVE domain-containing protein that is localized to EEA1-containing endosomes. It is regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Endofin is involved in Bone morphogenetic protein (BMP) signaling through interacting with Smad1 preferentially and enhancing Smad1 phosphorylation and nuclear localization upon BMP stimulation. It also functions as a scaffold protein that brings Smad4 to the proximity of the receptor complex in Transforming growth factor (TGF)-beta signaling. Moreover, endofin is a novel tyrosine phosphorylation target downstream of epidermal growth factor receptor (EGFR) in EGF-signaling. In addition, endofin plays a role in endosomal trafficking by recruiting cytosolic TOM1, an important molecule for membrane recruitment of clathrin, onto endosomal membranes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1910924708 276 QETPEWL-DSDS--CQKCDQPFfwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGfEFEVRVCDSCHEAI 351
Cdd:cd15729     2 KVAPVWVpDSEApnCMQCEVKF-----------TFTKRRHHCRACGKVLCSACCSLKARLEYLD-NKEARVCVPCYQTL 68

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), and similar proteins; This family includes protein containing both PH and FYVE domains 1 (phafin-1) and 2 (phafin-2). Phafin-1 is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway. Phafin-2 is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1910924708 310 RQHHCRKCGKAVCGKCSSKRSSIPLMGfEFEVRVCDSCH 348
Cdd:cd15717    24 RRHHCRKCGAVVCGACSSKKFLLPHQS-SKPLRVCDTCY 61

FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar proteins; WDFY3, also termed autophagy-linked FYVE protein (Alfy), is a ubiquitously expressed phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein required for selective macroautophagic degradation of aggregated proteins. It regulates the protein degradation through the direct interaction with the autophagy protein Atg5. Moreover, WDFY3 acts as a scaffold that bridges its cargo to the macroautophagic machinery via the creation of a greater complex with Atg12, Atg16L, and LC3. It also functionally associates with sequestosome-1/p62 (SQSTM1) in osteoclasts. WDFY3 shuttles between the nucleus and cytoplasm. It predominantly localizes to the nucleus and nuclear membrane under basal conditions, but is recruited to cytoplasmic ubiquitin-positive protein aggregates under stress conditions. WDFY3 contains a PH-BEACH domain assemblage, five WD40 repeats and a PtdIns3P-binding FYVE domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1910924708 285 DSCQKCDQPFfwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 348
Cdd:cd15719    10 DSCTGCSVRF-----------SLTERRHHCRNCGQLFCSKCSRFESEIRRLRISRPVRVCQACY 62

FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar proteins; Phafin-2, also termed endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), or pleckstrin homology domain-containing family F member 2 (PKHF2), or PH domain-containing family F member 2, or PH and FYVE domain-containing protein 2, or zinc finger FYVE domain-containing protein 18, is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1910924708 310 RQHHCRKCGKAVCGKCSSKRSSIPLMGFEfEVRVCDSCHEAI 351
Cdd:cd15755    24 RRHHCRKCGFVVCGPCSEKKFLLPSQSSK-PVRVCDFCYDLL 64

FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, also termed FYVE finger-containing phosphoinositide kinase, or 1-phosphatidylinositol 3-phosphate 5-kinase, or phosphatidylinositol 3-phosphate 5-kinase (PIP5K3), or phosphatidylinositol 3-phosphate 5-kinase type III (PIPkin-III or type III PIP kinase), is a phosphoinositide 5-kinase that forms a complex with its regulators, the scaffolding protein Vac14 and the lipid phosphatase Fig4. The complex is responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] from phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). Then phosphatidylinositol-5-phosphate (PtdIns5P) is generated directly from PtdIns(3,5)P2. PtdIns(3,5)P2 and PtdIns5P regulate endosomal trafficking and responses to extracellular stimuli. At this point, PIKfyve is vital in early embryonic development. Moreover, PIKfyve forms a complex with ArPIKfyve (associated regulator of PIKfyve) and SAC3 at the endomembranes, which plays a role in receptor tyrosine kinase (RTK) degradation. The phosphorylation of PIKfyve by AKT can facilitate Epidermal growth factor receptor (EGFR) degradation. In addition, PIKfyve may participate in the regulation of the glutamate transporters EAAT2, EAAT3 and EAAT4, and the cystic fibrosis transmembrane conductance regulator (CFTR). It is also essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. It can be activated by protein kinase B (PKB/Akt) and further up-regulates human ether-a-go-go (hERG) channels. This family also includes the yeast and plant orthologs of human PIKfyve, Fab1. PIKfyve and its orthologs share a similar architecture. They contain an N-terminal FYVE domain, a middle region related to the CCT/TCP-1/Cpn60 chaperonins that are involved in productive folding of actin and tubulin, a second middle domain that contains a number of conserved cysteine residues (CCR) unique to this family, and a C-terminal lipid kinase domain related to PtdInsP kinases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1910924708 281 WLDSDSCQ---KCDQPF-FWNfkqmwdsrkislRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCHE 349
Cdd:cd15725     2 WMPDSSCKecyECSEKFtTFR------------RRHHCRLCGQIFCSRCCNQEIPGKFIGYPGDLRVCTYCCK 62

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar proteins; FGD6, also termed zinc finger FYVE domain-containing protein 24 is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) whose biological function remains unclear. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Moreover, the FYVE domain of FGD6 is a canonical FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1910924708 307 ISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEfEVRVCDSC 347
Cdd:cd15743    21 VTWRRHHCRACGKVVCGSCSSNKAPLEYLKNK-SARVCDEC 60

FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar proteins; RUFY3, also termed Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. Moreover, the FYVE domain of RUFY3 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1910924708 286 SCQKCDQPFFwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEfEVRVCDSCH 348
Cdd:cd15744     1 SCSLCQEDFA----------SLALPKHNCYNCGGTFCDACSSNELPLPSSIYE-PARVCDVCY 52

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1910924708 190 TLVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWD 227
Cdd:pfam00400   2 KLLKTLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39

FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This family includes a group of uncharacterized rab GTPase-binding effector proteins found in bilateria. Although their biological functions remain unclear, they all contain a FYVE domain that harbors a putative phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding site.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1910924708 283 DSDSCQKCDQPFfwnfkqmwDSRKislRQHHCRKCGKAVCGKCSSKrsSIPLMGFEFEVRVCDSCH 348
Cdd:cd15739     9 DVDQCPNCKTPF--------SVGK---RKHHCRHCGKIFCSDCLTK--TVPSGPNRRPARVCDVCH 61

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar proteins; FGD3, also termed zinc finger FYVE domain-containing protein 5, is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) that undergoes the ubiquitin ligase SCFFWD1/beta-TrCP-mediated proteasomal degradation. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Due to this difference, FGD3 may play different roles from that of FGD1 to regulate cell morphology or motility. The FYVE domain of FGD3 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1910924708 283 DSDSCQKCDQPFfwNFkqmwdsrkISLRQHHCRKCGKAVCGKCSSKRSSIPLmgfefEVRVCDSC 347
Cdd:cd15740     4 EKQTCKGCNESF--NS--------ITKRRHHCKQCGAVICGKCSEFKDLASR-----HNRVCRDC 53

FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1910924708 287 CQKCDQPFfwnfkqmwdsrKISLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSC 347
Cdd:cd15745     2 CAICAKAF-----------SLFRRKYVCRLCGGVVCHSCSSEDLVLSVPDTCIYLRVCKTC 51

FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The family corresponds to the second FYVE domain that is responsible for the ability of Pep7p to efficiently interact with Vac1p and Vps45p.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1910924708 308 SLRQHHCRKCGKAVCG----KCSS------KRSSIPLMGFEFE------------VRVCDSC 347
Cdd:cd15737    21 LLRKHHCRLCGKVVCDdrrtKCSTevpldlLSSALPDLPFVFKepqsdipddtksVRVCRDC 82

FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and similar proteins; Rbsn-5, also termed zinc finger FYVE domain-containing protein 20, is a novel Rab5 effector that is complexed to the Sec1-like protein VPS45 and recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. It also binds to Rab4 and EHD1/RME-1, two regulators of the recycling route, and is involved in cargo recycling to the plasma membrane. Moreover, Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and plays a role of the apical endocytic trafficking of Fmi in the establishment of planar cell polarity (PCP).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1910924708 303 DSRKISLRQHHCRKCGKAVCGKCSSkrssiplmGFEFEVRVCDSC 347
Cdd:cd15716    18 KKFNLARRRHHCRLCGSIMCNKCSQ--------FLPLHIRCCHHC 54

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1910924708  237 ELQGHNDKIQALSYAQHTRQLISCGSDGGIVIWN 270
Cdd:smart00320   7 TLKGHTGPVTSVAFSPDGKYLASGSDDGTIKLWD 40

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and FYVE-related domain 1 found in yeast protein VAC1 (Vac1p) and similar proteins; The family includes Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and protein VAC1 (Vac1p). scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif. Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The FYVE domain in both Vps27p and Vac1p harbors a zinc-binding site composed of seven Cysteines and one Histidine, which is different from that of other FYVE domain containing proteins.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1910924708 304 SRKISL--RQHHCRKCGKAVCGKCSSKRSSIPLMGFEFE----VRVCDSC 347
Cdd:cd15736     6 SRTFNLniRAHHCRKCGKLFCRRHLPNMIPLNLSAYDPRngkwYRCCHSC 55

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1910924708 237 ELQGHNDKIQALSYAQHTRQLISCGSDGGIVIWN 270
Cdd:pfam00400   6 TLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39