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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063715498  559 ITGTDSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMAPktNRPYRVCDDCYIKLEG 624
Cdd:smart00064   5 IPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGI--ERPVRVCDDCYENLNG 68

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063715498  559 ITGTDSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMAPktNRPYRVCDDCYIKLEG 624
Cdd:smart00064   5 IPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGI--ERPVRVCDDCYENLNG 68

Regulator of chromosome condensation (RCC1) repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063715498 346 EGKLFTFGDGTFGALGHGDRISTNIPREVEALNGCRTIKAACGVWHSAAV 395
Cdd:pfam00415   1 DGRVYTWGRNDYGQLGLGTTENVLVPQKVEGLSGNKVVQVACGGDHTVAL 50

Alpha-tubulin suppressor ATS1 and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 224 QSISCGTNYAVLVTKQGQMYSWGEESGGRLGHGVCSYVPHPKLIDefNGSTVELADCGEFHTCAVTASGDLYAWGDGDHn 303
Cdd:COG5184     1 TQVAAGGSHSCALKSDGTVWCWGDNSYGQLGDGTTTDRSTPVRVP--GLSNVVAVAAGGDHTCALKADGTVWCWGNNSY- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 304 aGLLGLGSGASHWKPVRILGqmeGIYVKAISCGPWHTAFVTSEGKLFTFGDGTFGALGHGDRISTNIPREVEAlnGCRTI 383
Cdd:COG5184    78 -GQLGDGTTTDRTTPVKVPG---LTGVVAVAAGYYHSCALKSDGTVWCWGDNSSGQLGDGTTTNRLTPVQVDA--GLSGV 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 384 KA-ACGVWHSAAVvsvfgeaTSSGKLFTWGDGDDGRLGHGDIECRLIPSCVTELdtTSFQQVACGQSITVALSMSGQVYA 462
Cdd:COG5184   152 VAiAAGGYHTCAL-------KSDGTVWCWGANSYGQLGDGTTTDRPTPVQVGGL--SGVVAVAAGGDHSCALKSDGTVWC 222

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 463 MGT------ADPSHDIVRAPSCIEGGlgkSFVQEVACGFHHIAVLNSKAEVYTWGKGSNGQLGHGDTEYRCMPTLVKALK 536
Cdd:COG5184   223 WGSnssgqlGDGTTTDRATPVQVAGL---TGVVAIAAGGSHTCALKSDGTVWCWGDNSYGQLGDGTTTDRSTPVKVPGLS 299

                         330
                  ....*....|....
gi 1063715498 537 GkqVRKVVCGSNYT 550
Cdd:COG5184   300 G--VVAVAAGSSHT 311

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAmAPKTNRPYRVCDDCYIKLE 623
Cdd:pfam01363   8 SATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLLP-ELGSNKPVRVCDACYDTLQ 67

Regulator of chromosome condensation (RCC1) repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063715498 405 SGKLFTWGDGDDGRLGHGDIECRLIPSCVTELDTTSFQQVACGQSITVAL 454
Cdd:pfam00415   1 DGRVYTWGRNDYGQLGLGTTENVLVPQKVEGLSGNKVVQVACGGDHTVAL 50

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMapktNRPYRVCDDCYIKL 622
Cdd:cd15730     8 EVQNCMACGKGFSVTVRKHHCRQCGNIFCNECSSKTATTPSS----KKPVRVCDACFDDL 63

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. 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. RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCtSKKSLAAAMAPKtnrPYRVCDDCY 619
Cdd:cd15721     6 EVTHCQQCEKEFSLSRRKHHCRNCGGIFCNSC-SDNTMPLPSSAK---PVRVCDTCY 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063715498 556 HKPITGTDSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKsLAAAMAPKtnrPYRVCDDCY 619
Cdd:cd15758     4 HAWLKDDEATHCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNE-LALPSYPK---PVRVCDSCH 63

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKkslAAAMAPKtNRPYRVCDDCY 619
Cdd:cd15739     9 DVDQCPNCKTPFSVGKRKHHCRHCGKIFCSDCLTK---TVPSGPN-RRPARVCDVCH 61

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSkkslAAAMAPKTN--RPYRVCDDCYI 620
Cdd:cd15731    10 ACPQCMACSAPFTVLRRRHHCRNCGKIFCSRCSS----NSVPLPRYGqmKPVRVCNHCFM 65

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 564 STKCSGCRHPFNYMRKLHNCYNCGSVFCNS-CTSKKSLAAAmAPKTNrPYRVCDDCY 619
Cdd:cd15760     5 DSRCDVCRKKFGLFKRRHHCRNCGDSFCSEhSSRRIPLPHL-GPLGV-PQRVCDRCF 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063715498 565 TKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMapKTNRPYRVCDDCYIKL 622
Cdd:cd15719    10 DSCTGCSVRFSLTERRHHCRNCGQLFCSKCSRFESEIRRL--RISRPVRVCQACYNIL 65

FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063715498 563 DSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKslaaAMAPKTNRPYRVCDDCYIKL 622
Cdd:cd15759     9 EATHCKLCEKEFSLSKRKHHCRNCGEIFCNACSDNE----LPLPSSPKPVRVCDSCHAML 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 565 TKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKslaaAMAPKTN--RPYRVCDDCY 619
Cdd:cd15733     8 SHCFGCDCEFWLAKRKHHCRNCGNVFCADCSNYK----LPIPDEQlyDPVRVCNSCY 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063715498 567 CSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKslaaAMAPKTN--RPYRVCDDCY 619
Cdd:cd15732    11 CYGCEREFWLASRKHHCRNCGNVFCGSCCNQK----LPVPSQQlfEPSRVCKSCF 61

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 557 KPITGTDSTKCSGCRHPFNYM-RKLHNCYNCGSVFCNSCTSKKslaAAMAPKTNRPYRVCDDCYIKL 622
Cdd:cd15741     2 RWVRDNEVTMCMRCKEPFNALtRRRHHCRACGYVVCWKCSDYK---ATLEYDGNKLNRVCKHCYVIL 65

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1063715498 567 CSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMApkTNRPYRVCDDCY 619
Cdd:cd15727    13 CMSCKKKFDFFKRRHHCRRCGKCFCSDCCSNKVPLPRMC--FVDPVRVCNECA 63

FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar proteins; FYCO1, also termed zinc finger FYVE domain-containing protein 7, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport. It acts as an effector of GTP-bound Rab7, a GTPase that recruits FYCO1 to autophagosomes and has been implicated in autophagosome-lysosomal fusion. FYCO1 also interacts with two microtubule motor proteins, kinesin (KIF) 5B and KIF23, and thus functions as a platform for assembly of vesicle fusion and trafficking factors. FYCO1 contains an N-terminal alpha-helical RUN domain followed by a long central coiled-coil region, a FYVE domain and a GOLD (Golgi dynamics) domain in C-terminus.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063715498 562 TDSTKCSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMAPKTnrpyRVCDDCY 619
Cdd:cd15726     5 TDVTHCLDCKSEFSWMVRRHHCRLCGRIFCYACSNFYVLTAHGGKKE----RCCKACF 58

FYVE-related domain 1 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 first FYVE domain, which resembles the FYVE-related domain as it has an altered sequence in the basic ligand binding patch.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063715498 566 KCSGCRHPFNYMRKLHNCYNCGSVFCNS---CTSKKSLAAAMAPKTNRPYRVCDDCYIKLEG 624
Cdd:cd15761    12 RCSECGKTLNKKNGIVNCRKCGELFCNEhcrNRIKLNNSAEYDPKNGKWCRCCEKCFTSRPG 73

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063715498 567 CSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLaaamapktnrPYRVCDDCYIKLE 623
Cdd:cd15716    13 CPDCGKKFNLARRRHHCRLCGSIMCNKCSQFLPL----------HIRCCHHCKDLLE 59

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063715498 558 PITGTD-STKCSGCRhpFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMAPKtnrPYRVCDDCYIKL 622
Cdd:cd15754     4 PDKATDiCMRCTQTN--FSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPK---PVRVCSLCYRKL 64

Regulator of chromosome condensation (RCC1) repeat;

                          10        20
                  ....*....|....*....|....*....
gi 1063715498 330 VKAISCGPWHTAFVTSEGKLFTFGDGTFG 358
Cdd:pfam13540   1 VVSVAAGDNHTLALTSDGRVYCWGDNSYG 29

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063715498 567 CSGCRHPFNYMRKL-HNCYNCGSVFCNSCTSKKSLAAamapktnRPYRVCDDCY 619
Cdd:cd15740     8 CKGCNESFNSITKRrHHCKQCGAVICGKCSEFKDLAS-------RHNRVCRDCF 54

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.

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gi 1063715498 562 TDSTKCSGCRHPF--NYMRKL---------HNCYNCGSVFCNSCTSKKSLAAAMAPKTnrPYRVCDDCY 619
Cdd:cd15718     4 AESDNCQKCSRPFfwNFKQMWekktlgvrqHHCRKCGKAVCDKCSSNRSTIPVMGFEF--PVRVCNECY 70

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar proteins; FGD5, also termed zinc finger FYVE domain-containing protein 23, is an endothelial cell (EC)-specific guanine nucleotide exchange factor (GEF) that regulates endothelial adhesion, survival, and angiogenesis by modulating phosphatidylinositol 3-kinase signaling. It functions as a novel genetic regulator of vascular pruning by activation of endothelial cell-targeted apoptosis. FGD5 is a homologue of FGD1 and contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. The FYVE domain of FGD5 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.

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gi 1063715498 567 CSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAAMapkTNRPYRVCDDCYIKLE 623
Cdd:cd15742    12 CMNCGSDFTLTLRRHHCHACGKIVCRNCSRNKYPLKYL---KDRPAKVCDGCFAELR 65

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.

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gi 1063715498 567 CSGCRHPFNYMRKLHNCYNCGSVFCNSCTSKKSLAAamAPKTNRPYRVCDDCY 619
Cdd:cd15745     2 CAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDLVLS--VPDTCIYLRVCKTCY 52

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.

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gi 1063715498 563 DSTKCSGCRHPF--NYMR---------KLHNCYNCGSVFCNSCTSKKSLAAAMAPKTNrpYRVCDDCY 619
Cdd:cd15757     5 DSDSCQKCDQPFfwNFKQmwdskkiglRQHHCRKCGKAVCGKCSSKRSTIPLMGFEFE--VRVCDSCH 70