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 1958680109  11 DYNKMTPVKNYQAHQSRVTMVLFVLELEWVLSTGQDKQFAWHCSESGQRLGGYR--TSAVASgLQFDVESRHVFIGDHSG 88
Cdd:cd00200    79 DLETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNS-VAFSPDGTFVASSSQDG 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  89 QVTILKLEQENCtlLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIggRKGTAI-ELQGHNDKVQALSYAQHTRQ 167
Cdd:cd00200   158 TIKLWDLRTGKC--VATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDL--STGKCLgTLRGHENGVNSVAFSPDGYL 233

                         170
                  ....*....|....*.
gi 1958680109 168 LISCGGDGGIVVWNMD 183
Cdd:cd00200   234 LASGSEDGTIRVWDLR 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 1958680109  11 DYNKMTPVKNYQAHQSRVTMVLFVLELEWVLSTGQDKQFAWHCSESGQRLGGYR--TSAVASgLQFDVESRHVFIGDHSG 88
Cdd:cd00200    79 DLETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNS-VAFSPDGTFVASSSQDG 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  89 QVTILKLEQENCtlLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIggRKGTAI-ELQGHNDKVQALSYAQHTRQ 167
Cdd:cd00200   158 TIKLWDLRTGKC--VATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDL--STGKCLgTLRGHENGVNSVAFSPDGYL 233

                         170
                  ....*....|....*.
gi 1958680109 168 LISCGGDGGIVVWNMD 183
Cdd:cd00200   234 LASGSEDGTIRVWDLR 249

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 1958680109  190 PEWLD---SDSCQKCDQPFFWNfkqmwdskkigLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCHE 260
Cdd:smart00064   2 PHWIPdeeVSNCMGCGKEFNLT-----------KRRHHCRNCGRIFCSKCSSKKAPLPKLGIERPVRVCDDCYE 64

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1958680109  101 TLLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWD 138
Cdd:smart00320   3 ELLKTLKGHTGPVTSVAFSPDGKYLASGSDDGTIKLWD 40

phosphatidylinositol kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  190 PEWL----DSDSCQKCDQPFfwnfkqMWDSKKIGLRQHHCRKCGKAVCGKCSSKRS-------SIPLMGFEFEVR-VCDS 257
Cdd:PTZ00303   451 PSWQkddeSSDSCPSCGRAF------ISLSRPLGTRAHHCRSCGIRLCVFCITKRAhysfaklAKPGSSDEAEERlVCDT 524

                   ...
gi 1958680109  258 CHE 260
Cdd:PTZ00303   525 CYK 527

FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar proteins; 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. In addition to FYVE domain, WDFY1 harbors multiple WD-40 repeats.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958680109 190 PEWLDSDSCQKCDQPFFWNFKQMWDSKKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCHEAITDE 265
Cdd:cd15756     1 PQWLESDSCQKCEQPFFWNIKQMWDTKTLGLRQHHCRKCGQAVCGKCSSKRSSYPIMGFEFQVRVCDSCFETIKDE 76

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 1958680109  11 DYNKMTPVKNYQAHQSRVTMVLFVLELEWVLSTGQDKQFAWHCSESGQRLGGYR--TSAVASgLQFDVESRHVFIGDHSG 88
Cdd:cd00200    79 DLETGECVRTLTGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNS-VAFSPDGTFVASSSQDG 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  89 QVTILKLEQENCtlLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIggRKGTAI-ELQGHNDKVQALSYAQHTRQ 167
Cdd:cd00200   158 TIKLWDLRTGKC--VATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDL--STGKCLgTLRGHENGVNSVAFSPDGYL 233

                         170
                  ....*....|....*.
gi 1958680109 168 LISCGGDGGIVVWNMD 183
Cdd:cd00200   234 LASGSEDGTIRVWDLR 249

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  16 TPVKNYQAHQSRVTMVLFVLELEWVLSTGQDKQFA-WHcSESGQRLG--GYRTSAVASgLQFDVESRHVFIGDHSGQVTI 92
Cdd:COG2319   237 KLLRTLTGHSGSVRSVAFSPDGRLLASGSADGTVRlWD-LATGELLRtlTGHSGGVNS-VAFSPDGKLLASGSDDGTVRL 314

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  93 LKLEqeNCTLLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIGGRKGTAiELQGHNDKVQALSYAQHTRQLISCG 172
Cdd:COG2319   315 WDLA--TGKLLRTLTGHTGAVRSVAFSPDGKTLASGSDDGTVRLWDLATGELLR-TLTGHTGAVTSVAFSPDGRTLASGS 391

                         170
                  ....*....|.
gi 1958680109 173 GDGGIVVWNMD 183
Cdd:COG2319   392 ADGTVRLWDLA 402

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 1958680109  11 DYNKMTPVKNYQAHQSRVTMVLFVLELEWVLSTGQDKQ---FAWHCSESGQRLGGYrTSAVASgLQFDVESRHVFIGDHS 87
Cdd:cd00200    37 DLETGELLRTLKGHTGPVRDVAASADGTYLASGSSDKTirlWDLETGECVRTLTGH-TSYVSS-VAFSPDGRILSSSSRD 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  88 GQVTILKLEQENCtlLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIGGRKGTAiELQGHNDKVQALSYAQHTRQ 167
Cdd:cd00200   115 KTIKVWDVETGKC--LTTLRGHTDWVNSVAFSPDGTFVASSSQDGTIKLWDLRTGKCVA-TLTGHTGEVNSVAFSPDGEK 191

                         170       180
                  ....*....|....*....|
gi 1958680109 168 LISCGGDGGIVVWNMDVERQ 187
Cdd:cd00200   192 LLSSSSDGTIKLWDLSTGKC 211

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 1958680109  72 LQFDVESRHVFIGDHSGQVTILKLEqeNCTLLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIGGRKgTAIELQG 151
Cdd:cd00200    15 VAFSPDGKLLATGSGDGTIKVWDLE--TGELLRTLKGHTGPVRDVAASADGTYLASGSSDKTIRLWDLETGE-CVRTLTG 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109 152 HNDKVQALSYAQHTRQLISCGGDGGIVVWNmdverqetpewLDSDSCQKCdqpffwnfkqmwdskkigLRQH-----HCR 226
Cdd:cd00200    92 HTSYVSSVAFSPDGRILSSSSRDKTIKVWD-----------VETGKCLTT------------------LRGHtdwvnSVA 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109 227 --KCGKAVCGkCSSKRSsiplmgfefeVRVCDscheaiTDEERaPTATFHDSKHNIVHVHFDATRGWLLTAGTDKVIKLW 304
Cdd:cd00200   143 fsPDGTFVAS-SSQDGT----------IKLWD------LRTGK-CVATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLW 204

                  ..
gi 1958680109 305 DM 306
Cdd:cd00200   205 DL 206

FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 (spVps27p) and similar proteins; spVps27p, also termed suppressor of ste12 deletion protein 4 (Sst4p), is a conserved homolog of budding Saccharomyces cerevisiae Vps27 and of mammalian Hrs. It functions as a downstream factor for phosphatidylinositol 3-kinase (PtdIns 3-kinase) in forespore membrane formation with normal morphology. It colocalizes and interacts with Hse1p, a homolog of Saccharomyces cerevisiae Hse1p and of mammalian STAM, to form a complex whose ubiquitin-interacting motifs (UIMs) are important for sporulation. spVps27p contains a VHS (Vps27p/Hrs/Stam) domain, a FYVE domain, and two UIMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958680109 190 PEWLDSDSCQKCDQPF-FWNfkqmwdskkiglRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 259
Cdd:cd15735     1 PEWVDSDVCMRCRTAFtFTN------------RKHHCRNCGGVFCQQCSSKSLPLPHFGINQPVRVCDGCY 59

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 1958680109 197 SCQKCDQPFFWNFkqmwdskkiglRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 259
Cdd:cd00065     1 RCMLCGKKFSLFR-----------RRHHCRRCGRVFCSKCSSKKLPLPSFGSGKPVRVCDSCY 52

FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed endosome-associated protein p162, or zinc finger FYVE domain-containing protein 2, is an essential component of the endosomal fusion machinery and required for the fusion and maturation of early endosomes in endocytosis. It forms a parallel coiled-coil homodimer in cells. EEA1 serves as the p97 ATPase substrate and the p97 ATPase may regulate the size of early endosomes by governing the oligomeric state of EEA1. It can interact with the GTP-bound form of Rab22a and be involved in endosomal membrane trafficking. EEA1 also functions as an obligate scaffold for angiotensin II-induced Akt activation in early endosomes. It can be phosphorylated by p38 mitogen-activated protein kinase (MAPK) and further regulate mu opioid receptor endocytosis. EEA1 consists of an N-terminal C2H2 Zn2+ finger, four long heptad repeats, and a C-terminal region containing a calmodulin binding (IQ) motif, a Rab5 interaction site, and a FYVE domain. This model corresponds to the FYVE domain that is responsible for binding phosphatidyl inositol-3-phosphate (PtdIns3P or PI3P) on the membrane.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958680109 190 PEWLD---SDSCQKCDQPFfwnfkqmwdskKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMgfEFEVRVCDSC 258
Cdd:cd15730     1 RKWADdeeVQNCMACGKGF-----------SVTVRKHHCRQCGNIFCNECSSKTATTPSS--KKPVRVCDAC 59

FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ZF21 is phosphoinositide-binding protein that functions as a regulator of focal adhesions and cell movement through interaction with focal adhesion kinase. It can also bind to the cytoplasmic tail of membrane type 1 matrix metalloproteinase, a potent invasion-promoting protease, and play a key role in regulating multiple aspects of cancer cell migration and invasion. ZF21 contains a FYVE domain, which corresponds to this model.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958680109 190 PEWLDSDSCQKCDqpffwNFKQMWDSKKiglRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSC 258
Cdd:cd15727     2 PPWVPDKECPVCM-----SCKKKFDFFK---RRHHCRRCGKCFCSDCCSNKVPLPRMCFVDPVRVCNEC 62

FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958680109 192 WLDSDS---CQKCDQPFfwnfkqmwdskKIGLRQHHCRKCGKAVCGKCSSKRSSIPlmGFEFEVRVCDSCH 259
Cdd:cd15758     6 WLKDDEathCKQCEKEF-----------SISRRKHHCRNCGHIFCNTCSSNELALP--SYPKPVRVCDSCH 63

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 1958680109 187 QETPEWL-DSDS--CQKCDQPFfwnfkqmwdskKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGfEFEVRVCDSCHEAI 262
Cdd:cd15729     2 KVAPVWVpDSEApnCMQCEVKF-----------TFTKRRHHCRACGKVLCSACCSLKARLEYLD-NKEARVCVPCYQTL 68

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and similar proteins; 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958680109 192 WLDSDSCQKCDQPFFWnFKqmwdskkiglRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFE-VRVCDSCH 259
Cdd:cd15760     2 WKPDSRCDVCRKKFGL-FK----------RRHHCRNCGDSFCSEHSSRRIPLPHLGPLGVpQRVCDRCF 59

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958680109 198 CQKCDQPFFwnfkqmwdskkIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 259
Cdd:cd15733    10 CFGCDCEFW-----------LAKRKHHCRNCGNVFCADCSNYKLPIPDEQLYDPVRVCNSCY 60

FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed FYVE domain-containing centrosomal protein (FYVE-CENT), or spastizin, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that localizes to the centrosome and midbody. ZFY26 and its interacting partners TTC19 and KIF13A are required for cytokinesis. It also interacts with Beclin 1, a subunit of class III phosphatidylinositol 3-kinase complex, and may have potential implications for carcinogenesis. In addition, it has been considered as the causal agent of a rare form of hereditary spastic paraplegia. ZFY26 contains a FYVE domain that is important for targeting of FYVE-CENT to the midbody.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958680109 221 RQHHCRKCGKAVCGKCSSKRSSIPLMGfEFEVRVCDSCHE 260
Cdd:cd15724    23 RRHHCRRCGRVVCSSCSTKKMLVEGYR-ENPVRVCDQCYE 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 1958680109 196 DSCQKCDQPFfwnfkqmwdskKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 259
Cdd:cd15719    10 DSCTGCSVRF-----------SLTERRHHCRNCGQLFCSKCSRFESEIRRLRISRPVRVCQACY 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
                  ....*....|....*....|....*....|....*...
gi 1958680109 221 RQHHCRKCGKAVCGKCSSKRSSIPLMGFEfEVRVCDSC 258
Cdd:cd15743    24 RRHHCRACGKVVCGSCSSNKAPLEYLKNK-SARVCDEC 60

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1958680109  101 TLLTSFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWD 138
Cdd:smart00320   3 ELLKTLKGHTGPVTSVAFSPDGKYLASGSDDGTIKLWD 40

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 1958680109 197 SCQKCDQPFFWNFKQmwdskkiglrQHHCRKCGKAVCGKCSSKRSSIPLMGFEfEVRVCDSCH 259
Cdd:cd15744     1 SCSLCQEDFASLALP----------KHNCYNCGGTFCDACSSNELPLPSSIYE-PARVCDVCY 52

FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also termed Myotubularin-related phosphatase 3, or FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1), or zinc finger FYVE domain-containing protein 10, is a ubiquitously expressed phosphoinositide 3-phosphatase specific for phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and PIKfyve, which produces PtdIns(3,5)P2 from PtdIns3P. It regulates cell migration through modulating phosphatidylinositol 5-phosphate (PtdIns5P) levels. MTMR3 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain. Unlike conventional FYVE domains, the FYVE domain of MTMR3 neither confers endosomal localization nor binds to PtdIns3P. It is also not required for the enzyme activity of MTMR3. In contrast, the PH-G domain binds phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109 192 WLD---SDSCQKCDQPFFwnfkqmwdskkIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSC 258
Cdd:cd15732     2 WVPdhlAASCYGCEREFW-----------LASRKHHCRNCGNVFCGSCCNQKLPVPSQQLFEPSRVCKSC 60

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the 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. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958680109 190 PEWLDSDS---CQKCDQPFFWNFKqmwdskkiglRQHHCRKCGKAVCGKCSSKRSSIPLMGfEFEVRVCDSCHEAI 262
Cdd:cd15741     1 PRWVRDNEvtmCMRCKEPFNALTR----------RRHHCRACGYVVCWKCSDYKATLEYDG-NKLNRVCKHCYVIL 65

phosphatidylinositol kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958680109  190 PEWL----DSDSCQKCDQPFfwnfkqMWDSKKIGLRQHHCRKCGKAVCGKCSSKRS-------SIPLMGFEFEVR-VCDS 257
Cdd:PTZ00303   451 PSWQkddeSSDSCPSCGRAF------ISLSRPLGTRAHHCRSCGIRLCVFCITKRAhysfaklAKPGSSDEAEERlVCDT 524

                   ...
gi 1958680109  258 CHE 260
Cdd:PTZ00303   525 CYK 527

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 1958680109 194 DSDSCQKCDQPFfwNFkqmwdskkIGLRQHHCRKCGKAVCGKCSSKRSSIPLmgfefEVRVCDSC 258
Cdd:cd15740     4 EKQTCKGCNESF--NS--------ITKRRHHCKQCGAVICGKCSEFKDLASR-----HNRVCRDC 53

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 1958680109 220 LRQHHCRKCGKAVCG----KCSS------KRSSIPLMGFEFE------------VRVCDSC 258
Cdd:cd15737    22 LRKHHCRLCGKVVCDdrrtKCSTevpldlLSSALPDLPFVFKepqsdipddtksVRVCRDC 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
                  ....*....|....*....|....*....|....*...
gi 1958680109 221 RQHHCRKCGKAVCGKCSSkrssiplmGFEFEVRVCDSC 258
Cdd:cd15716    25 RRHHCRLCGSIMCNKCSQ--------FLPLHIRCCHHC 54

FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from eumetazoa; This family includes a group of uncharacterized myotubularin-related proteins mainly found in eumetazoa. Although their biological functions remain unclear, they share similar domain architecture that consists of an N-terminal pleckstrin homology (PH) domain, a highly conserved region related to myotubularin proteins, a C-terminal FYVE domain. The model corresponds to the FYVE domain, which resembles the FYVE-related domain as it has an altered sequence in the basic ligand binding patch.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1958680109 221 RQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCH 259
Cdd:cd15738    23 KKHHCWRCGNVFCTRCIDKQRALPGHLSQRPVPVCRACY 61

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 1958680109 215 SKKIGL--RQHHCRKCGKAVCGKCSSKRSSIPLMGFEFE----VRVCDSC 258
Cdd:cd15736     6 SRTFNLniRAHHCRKCGKLFCRRHLPNMIPLNLSAYDPRngkwYRCCHSC 55

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1958680109 148 ELQGHNDKVQALSYAQHTRQLISCGGDGGIVVWN 181
Cdd:pfam00400   6 TLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39