NCBI Conserved Domain Search

Guanylate-binding protein (GBP) family (N-terminal domain); Guanylate-binding protein (GBP), N-terminal domain. Guanylate-binding proteins (GBPs) define a group of proteins that are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. Furthermore, two unique regions around the base and the phosphate-binding areas, the guanine and the phosphate caps, respectively, give the nucleotide-binding site a unique appearance not found in the canonical GTP-binding proteins. The phosphate cap, which constitutes the region analogous to switch I, completely shields the phosphate-binding site from solvent such that a potential GTPase-activating protein (GAP) cannot approach.

Pssm-ID: 206650 Cd Length: 224 Bit Score: 194.08 E-value: 4.32e-57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 174 CKPDQHLKVVSIFGNTGDGKSHTLNHTFFYGrEVFKTSPTQESCTVGVWAAYDPV-------HKVAVIDTEGLLGATVNL 246
Cdd:cd01851    1 LDVGFPVVVVSVFGSQSSGKSFLLNHLFGTS-DGFDVMDTSQQTTKGIWMWSDPFkdtdgkkHAVLLLDTEGTDGRERGE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 247 -SQRTRLLLKVLAISDLVIYRTHADRLHNDLFKFLGDASEAylkhftkelkattarcgldvpLSTLGPAVIIFHETVHTQ 325
Cdd:cd01851   80 fENDARLFALATLLSSVLIYNMWQTILGDDLDKLMGLLKTA---------------------LETLGLAGLHNFSKPKPL 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 326 LLGSDHPSEVPEKLIQD-----RFRKLGRFPEAFSSIHYKGTrtynPPTDFSGLRRALEQLLENNTTRSPRHPGVIFKAL 400
Cdd:cd01851  139 LLFVVRDFTGPTPLEGLdvtekSETLIEELNKIWSSIRKPFT----PITCFVLPHPGLLHKLLQNDGRLKDLPPEFRKAL 214

                        250
                 ....*....|
gi 528524508 401 KALSDRFSGE 410
Cdd:cd01851  215 KALRQRFFSS 224

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.

Pssm-ID: 277273 [Multi-domain] Cd Length: 61 Bit Score: 123.21 E-value: 1.02e-33

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 697 YWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCN 757
Cdd:cd15734    1 YWVPDSEIKECSVCKRPFSPRLSKHHCRACGQGVCDDCSKNRRPVPSRGWDHPVRVCDPCA 61

second B-box-type 1 zinc finger found in zinc finger FYVE domain-containing protein 1 (ZFYVE1) and similar proteins; ZFYVE1 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 ZFYVE1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by Wortmannin, a PI3-kinase inhibitor. ZFYVE1 harbors two B-box motifs, both of which show high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs). The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

Pssm-ID: 380878 Cd Length: 59 Bit Score: 106.58 E-value: 5.96e-28

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508  69 PYCDLCKGLSGHL-----PGVRQRAIVRCQTCKINLCLECQKRTHSGGNKRRHPVTVYN 122
Cdd:cd19820    1 PYCDSCKGGNGNSmhsstAGSRQRAAVRCQSCKINLCPECQKRTHSGGNKRKHPVTVYP 59

first B-box-type 1 zinc finger found in zinc finger FYVE domain-containing protein 1 (ZFYVE1) and similar proteins; ZFYVE1 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 ZFYVE1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by Wortmannin, a PI3-kinase inhibitor. ZFYVE1 harbors two B-box motifs, both of which show high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs). The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

Pssm-ID: 380877 Cd Length: 48 Bit Score: 96.04 E-value: 2.15e-24

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 528524508  16 LMCQESYACSGTDEAIFECDECCSLQCLRCEEELHRQERLRNHERIRL 63
Cdd:cd19819    1 LMCQESYACSGSDEAVFECDECGSLQCQRCEKELHQQERLRNHERTRI 48

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.

Pssm-ID: 277273 [Multi-domain] Cd Length: 61 Bit Score: 89.31 E-value: 7.84e-22

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 580 YWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCY 641
Cdd:cd15734    1 YWVPDSEIKECSVCKRPFSPRLSKHHCRACGQGVCDDCSKNRRPVPSRGW-DHPVRVCDPCA 61

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.

Pssm-ID: 426221 [Multi-domain] Cd Length: 68 Bit Score: 83.58 E-value: 9.62e-20

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528524508  579 AYWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGPAPVRVCDNCYEA 643
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLLPELGSNKPVRVCDACYDT 65

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.

Pssm-ID: 426221 [Multi-domain] Cd Length: 68 Bit Score: 83.58 E-value: 9.81e-20

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508  696 AYWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAV-PSRGWDHPVRVCFNC 756
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLlPELGSNKPVRVCDAC 62

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.

Pssm-ID: 277261 [Multi-domain] Cd Length: 58 Bit Score: 77.42 E-value: 1.16e-17

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwdHPVRVCFNCN 757
Cdd:cd15721    1 WADDKEVTHCQQCEKEFSLSRRKHHCRNCGGIFCNSCSDNTMPLPSSA--KPVRVCDTCY 58

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.

Pssm-ID: 277269 [Multi-domain] Cd Length: 63 Bit Score: 74.74 E-value: 1.05e-16

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSrgWDHPVRVCFNC 756
Cdd:cd15730    3 WADDEEVQNCMACGKGFSVTVRKHHCRQCGNIFCNECSSKTATTPS--SKKPVRVCDAC 59

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.

Pssm-ID: 214499 [Multi-domain] Cd Length: 68 Bit Score: 74.78 E-value: 1.31e-16

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528524508   696 AYWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCNKK 759
Cdd:smart00064   2 PHWIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIERPVRVCDDCYEN 65

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.

Pssm-ID: 277272 [Multi-domain] Cd Length: 60 Bit Score: 73.23 E-value: 3.40e-16

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15733    1 WVPDHAASHCFGCDCEFWLAKRKHHCRNCGNVFCADCSNYKLPIPDEQLYDPVRVCNSC 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.

Pssm-ID: 277266 [Multi-domain] Cd Length: 64 Bit Score: 71.25 E-value: 1.66e-15

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 697 YWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15727    3 PWVPDKECPVCMSCKKKFDFFKRRHHCRRCGKCFCSDCCSNKVPLPRMCFVDPVRVCNEC 62

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.

Pssm-ID: 277270 [Multi-domain] Cd Length: 65 Bit Score: 70.07 E-value: 5.26e-15

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 694 RPAYWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15731    1 DPPLWVPDEACPQCMACSAPFTVLRRRHHCRNCGKIFCSRCSSNSVPLPRYGQMKPVRVCNHC 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.

Pssm-ID: 277261 [Multi-domain] Cd Length: 58 Bit Score: 68.95 E-value: 9.12e-15

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPErgwGPAPVRVCDNCY 641
Cdd:cd15721    1 WADDKEVTHCQQCEKEFSLSRRKHHCRNCGGIFCNSCSDNTMPLPS---SAKPVRVCDTCY 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.

Pssm-ID: 277297 [Multi-domain] Cd Length: 71 Bit Score: 68.94 E-value: 1.62e-14

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSrgWDHPVRVCFNCN 757
Cdd:cd15758    6 WLKDDEATHCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPS--YPKPVRVCDSCH 63

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.

Pssm-ID: 277249 [Multi-domain] Cd Length: 52 Bit Score: 66.40 E-value: 6.23e-14

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 528524508 706 HCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd00065    1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSFGSGKPVRVCDSC 51

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.

Pssm-ID: 277269 [Multi-domain] Cd Length: 63 Bit Score: 66.65 E-value: 7.91e-14

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPErgwGPAPVRVCDNCY 641
Cdd:cd15730    3 WADDEEVQNCMACGKGFSVTVRKHHCRQCGNIFCNECSSKTATTPS---SKKPVRVCDACF 60

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.

Pssm-ID: 277260 [Multi-domain] Cd Length: 61 Bit Score: 66.64 E-value: 8.10e-14

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528524508 707 CHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCNKK 759
Cdd:cd15720    8 CHRCRVQFGVFQRKHHCRACGQVFCGKCSSKSSTIPKFGIEKEVRVCDPCYEK 60

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.

Pssm-ID: 214499 [Multi-domain] Cd Length: 68 Bit Score: 66.69 E-value: 9.73e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528524508   579 AYWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGPaPVRVCDNCYEARN 645
Cdd:smart00064   2 PHWIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIER-PVRVCDDCYENLN 67

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.

Pssm-ID: 277271 [Multi-domain] Cd Length: 61 Bit Score: 65.69 E-value: 1.66e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 697 YWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15732    1 RWVPDHLAASCYGCEREFWLASRKHHCRNCGNVFCGSCCNQKLPVPSQQLFEPSRVCKSC 60

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.

Pssm-ID: 277274 [Multi-domain] Cd Length: 59 Bit Score: 63.70 E-value: 7.39e-13

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528524508 590 CNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGpAPVRVCDNCY 641
Cdd:cd15735    9 CMRCRTAFTFTNRKHHCRNCGGVFCQQCSSKSLPLPHFGIN-QPVRVCDGCY 59

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.

Pssm-ID: 277260 [Multi-domain] Cd Length: 61 Bit Score: 62.02 E-value: 3.65e-12

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 528524508 590 CNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCYEA 643
Cdd:cd15720    8 CHRCRVQFGVFQRKHHCRACGQVFCGKCSSKSSTIPKFGI-EKEVRVCDPCYEK 60

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.

Pssm-ID: 277270 [Multi-domain] Cd Length: 65 Bit Score: 61.21 E-value: 7.58e-12

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528524508 578 PAYWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGpAPVRVCDNCY 641
Cdd:cd15731    2 PPLWVPDEACPQCMACSAPFTVLRRRHHCRNCGKIFCSRCSSNSVPLPRYGQM-KPVRVCNHCF 64

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.

Pssm-ID: 277266 [Multi-domain] Cd Length: 64 Bit Score: 59.70 E-value: 1.92e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 580 YWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPeRGWGPAPVRVCDNCYE 642
Cdd:cd15727    3 PWVPDKECPVCMSCKKKFDFFKRRHHCRRCGKCFCSDCCSNKVPLP-RMCFVDPVRVCNECAL 64

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.

Pssm-ID: 277249 [Multi-domain] Cd Length: 52 Bit Score: 59.47 E-value: 1.96e-11

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528524508 589 SCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGpAPVRVCDNCY 641
Cdd:cd00065    1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSFGSG-KPVRVCDSCY 52

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.

Pssm-ID: 277297 [Multi-domain] Cd Length: 71 Bit Score: 58.92 E-value: 5.10e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERgwgPAPVRVCDNCY 641
Cdd:cd15758    6 WLKDDEATHCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNELALPSY---PKPVRVCDSCH 63

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.

Pssm-ID: 277271 [Multi-domain] Cd Length: 61 Bit Score: 57.60 E-value: 1.18e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 580 YWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPeRGWGPAPVRVCDNCY 641
Cdd:cd15732    1 RWVPDHLAASCYGCEREFWLASRKHHCRNCGNVFCGSCCNQKLPVP-SQQLFEPSRVCKSCF 61

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.

Pssm-ID: 277298 [Multi-domain] Cd Length: 71 Bit Score: 57.73 E-value: 1.49e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRgwDHPVRVCFNCN 757
Cdd:cd15759    4 WLKDKEATHCKLCEKEFSLSKRKHHCRNCGEIFCNACSDNELPLPSS--PKPVRVCDSCH 61

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.

Pssm-ID: 277264 [Multi-domain] Cd Length: 62 Bit Score: 56.95 E-value: 1.86e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 697 YWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCNK 758
Cdd:cd15725    1 YWMPDSSCKECYECSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFIGYPGDLRVCTYCCK 62

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.

Pssm-ID: 277259 [Multi-domain] Cd Length: 65 Bit Score: 57.01 E-value: 2.37e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 697 YWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15719    2 HWVKDEGGDSCTGCSVRFSLTERRHHCRNCGQLFCSKCSRFESEIRRLRISRPVRVCQAC 61

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.

Pssm-ID: 277258 [Multi-domain] Cd Length: 70 Bit Score: 56.18 E-value: 5.18e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528524508 693 ARPAYWvpdheilhchNCRKEFSIK---LSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCN 757
Cdd:cd15718   13 SRPFFW----------NFKQMWEKKtlgVRQHHCRKCGKAVCDKCSSNRSTIPVMGFEFPVRVCNECY 70

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.

Pssm-ID: 277274 [Multi-domain] Cd Length: 59 Bit Score: 55.61 E-value: 5.69e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 528524508 707 CHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15735    9 CMRCRTAFTFTNRKHHCRNCGGVFCQQCSSKSLPLPHFGINQPVRVCDGC 58

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.

Pssm-ID: 277299 [Multi-domain] Cd Length: 59 Bit Score: 55.38 E-value: 7.10e-10

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528524508 589 SCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGPAPVRVCDNCY 641
Cdd:cd15760    7 RCDVCRKKFGLFKRRHHCRNCGDSFCSEHSSRRIPLPHLGPLGVPQRVCDRCF 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.

Pssm-ID: 277272 [Multi-domain] Cd Length: 60 Bit Score: 55.13 E-value: 9.35e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCY 641
Cdd:cd15733    1 WVPDHAASHCFGCDCEFWLAKRKHHCRNCGNVFCADCSNYKLPIPDEQL-YDPVRVCNSCY 60

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.

Pssm-ID: 277257 [Multi-domain] Cd Length: 61 Bit Score: 54.68 E-value: 1.23e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRK-EFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwDHPVRVCFNC 756
Cdd:cd15717    2 WVPDSEAPVCMHCKKtKFTAINRRHHCRKCGAVVCGACSSKKFLLPHQS-SKPLRVCDTC 60

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.

Pssm-ID: 277278 [Multi-domain] Cd Length: 73 Bit Score: 54.27 E-value: 2.05e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECShdRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15739    4 WQHEDDVDQCPNCKTPFSVGKRKHHCRHCGKIFCSDCL--TKTVPSGPNRRPARVCDVC 60

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.

Pssm-ID: 277298 [Multi-domain] Cd Length: 71 Bit Score: 54.26 E-value: 2.62e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPErgwGPAPVRVCDNCY 641
Cdd:cd15759    4 WLKDKEATHCKLCEKEFSLSKRKHHCRNCGEIFCNACSDNELPLPS---SPKPVRVCDSCH 61

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.

Pssm-ID: 277258 [Multi-domain] Cd Length: 70 Bit Score: 53.86 E-value: 2.63e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528524508 589 SCNKCATSFKDN-----DTK------HHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCY 641
Cdd:cd15718    8 NCQKCSRPFFWNfkqmwEKKtlgvrqHHCRKCGKAVCDKCSSNRSTIPVMGF-EFPVRVCNECY 70

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.

Pssm-ID: 277299 [Multi-domain] Cd Length: 59 Bit Score: 53.45 E-value: 3.02e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528524508 706 HCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWD-HPVRVCFNC 756
Cdd:cd15760    7 RCDVCRKKFGLFKRRHHCRNCGDSFCSEHSSRRIPLPHLGPLgVPQRVCDRC 58

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.

Pssm-ID: 277278 [Multi-domain] Cd Length: 73 Bit Score: 53.50 E-value: 4.27e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVpergwGPA--PVRVCDNCY 641
Cdd:cd15739    4 WQHEDDVDQCPNCKTPFSVGKRKHHCRHCGKIFCSDCLTKTVPS-----GPNrrPARVCDVCH 61

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.

Pssm-ID: 277295 [Multi-domain] Cd Length: 76 Bit Score: 53.15 E-value: 5.69e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528524508 589 SCNKCATSFKDN-----DTK------HHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCYEA 643
Cdd:cd15756    8 SCQKCEQPFFWNikqmwDTKtlglrqHHCRKCGQAVCGKCSSKRSSYPIMGF-EFQVRVCDSCFET 72

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.

Pssm-ID: 277294 [Multi-domain] Cd Length: 64 Bit Score: 52.73 E-value: 7.06e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 698 WVPDHEILHCHNCRK-EFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwDHPVRVCFNCNK 758
Cdd:cd15755    2 WVPDSEATVCMRCQKaKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQS-SKPVRVCDFCYD 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.

Pssm-ID: 277282 [Multi-domain] Cd Length: 61 Bit Score: 52.05 E-value: 8.98e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECShDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15743    3 WIPDSRVTMCMICTSEFTVTWRRHHCRACGKVVCGSCS-SNKAPLEYLKNKSARVCDEC 60

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.

Pssm-ID: 277294 [Multi-domain] Cd Length: 64 Bit Score: 51.96 E-value: 1.17e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 581 WRPNSQILSCNKC-ATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERgwGPAPVRVCDNCYE 642
Cdd:cd15755    2 WVPDSEATVCMRCqKAKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQ--SSKPVRVCDFCYD 62

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).

Pssm-ID: 277256 [Multi-domain] Cd Length: 61 Bit Score: 51.96 E-value: 1.22e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECshdrravpSRGWDHPVRVCFNC 756
Cdd:cd15716    4 WVNDSDVPFCPDCGKKFNLARRRHHCRLCGSIMCNKC--------SQFLPLHIRCCHHC 54

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.

Pssm-ID: 277263 [Multi-domain] Cd Length: 61 Bit Score: 51.75 E-value: 1.44e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKE-FSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwDHPVRVCFNC 756
Cdd:cd15724    1 WVPDEAVSVCMVCQVErFSMFNRRHHCRRCGRVVCSSCSTKKMLVEGYR-ENPVRVCDQC 59

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.

Pssm-ID: 277268 [Multi-domain] Cd Length: 68 Bit Score: 51.59 E-value: 1.83e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 695 PAYWVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHdRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15729    4 APVWVPDSEAPNCMQCEVKFTFTKRRHHCRACGKVLCSACCS-LKARLEYLDNKEARVCVPC 64

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.

Pssm-ID: 277257 [Multi-domain] Cd Length: 61 Bit Score: 50.83 E-value: 2.51e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 581 WRPNSQILSCNKCA-TSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERgwGPAPVRVCDNCY 641
Cdd:cd15717    2 WVPDSEAPVCMHCKkTKFTAINRRHHCRKCGAVVCGACSSKKFLLPHQ--SSKPLRVCDTCY 61

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.

Pssm-ID: 277282 [Multi-domain] Cd Length: 61 Bit Score: 50.90 E-value: 2.97e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVpeRGWGPAPVRVCDNCY 641
Cdd:cd15743    3 WIPDSRVTMCMICTSEFTVTWRRHHCRACGKVVCGSCSSNKAPL--EYLKNKSARVCDECF 61

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.

Pssm-ID: 277295 [Multi-domain] Cd Length: 76 Bit Score: 50.84 E-value: 4.10e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 707 CHNCRKEF-----------SIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15756    9 CQKCEQPFfwnikqmwdtkTLGLRQHHCRKCGQAVCGKCSSKRSSYPIMGFEFQVRVCDSC 69

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.

Pssm-ID: 277259 [Multi-domain] Cd Length: 65 Bit Score: 50.46 E-value: 4.31e-08

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528524508 589 SCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPeRGWGPAPVRVCDNCY 641
Cdd:cd15719   11 SCTGCSVRFSLTERRHHCRNCGQLFCSKCSRFESEIR-RLRISRPVRVCQACY 62

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.

Pssm-ID: 277267 [Multi-domain] Cd Length: 63 Bit Score: 49.34 E-value: 1.03e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 528524508 589 SCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGpAPVRVCDNCYE 642
Cdd:cd15728    9 YCYECGVKFGITTRKHHCRHCGRLLCSKCSTKEVPIIKFDLN-KPVRVCDVCFD 61

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.

Pssm-ID: 277263 [Multi-domain] Cd Length: 61 Bit Score: 49.05 E-value: 1.05e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 581 WRPNSQILSCNKCATS-FKDNDTKHHCRACGEGFCDSCSSKTRPVpeRGWGPAPVRVCDNCYE 642
Cdd:cd15724    1 WVPDEAVSVCMVCQVErFSMFNRRHHCRRCGRVVCSSCSTKKMLV--EGYRENPVRVCDQCYE 61

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.

Pssm-ID: 277268 [Multi-domain] Cd Length: 68 Bit Score: 49.27 E-value: 1.12e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528524508 578 PAYWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSS-KTR-PVPERgwgpAPVRVCDNCYEA 643
Cdd:cd15729    4 APVWVPDSEAPNCMQCEVKFTFTKRRHHCRACGKVLCSACCSlKARlEYLDN----KEARVCVPCYQT 67

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.

Pssm-ID: 277267 [Multi-domain] Cd Length: 63 Bit Score: 48.96 E-value: 1.57e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 528524508 707 CHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15728   10 CYECGVKFGITTRKHHCRHCGRLLCSKCSTKEVPIIKFDLNKPVRVCDVC 59

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.

Pssm-ID: 277265 [Multi-domain] Cd Length: 58 Bit Score: 47.94 E-value: 3.07e-07

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwdHPVRVCFNC 756
Cdd:cd15726    1 WQDDTDVTHCLDCKSEFSWMVRRHHCRLCGRIFCYACSNFYVLTAHGG--KKERCCKAC 57

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.

Pssm-ID: 277293 [Multi-domain] Cd Length: 64 Bit Score: 47.64 E-value: 4.52e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 698 WVPDHEILHCHNC-RKEFSIKLSKHHCRACGQGFCDECSHDRRAVPsRGWDHPVRVCFNCNKK 759
Cdd:cd15754    2 WIPDKATDICMRCtQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIP-RLSPKPVRVCSLCYRK 63

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.

Pssm-ID: 277264 [Multi-domain] Cd Length: 62 Bit Score: 47.32 E-value: 5.48e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528524508 580 YWRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCYE 642
Cdd:cd15725    1 YWMPDSSCKECYECSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFIGY-PGDLRVCTYCCK 62

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.

Pssm-ID: 277296 [Multi-domain] Cd Length: 70 Bit Score: 46.60 E-value: 1.24e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 528524508 716 IKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCN 757
Cdd:cd15757   29 IGLRQHHCRKCGKAVCGKCSSKRSTIPLMGFEFEVRVCDSCH 70

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.

Pssm-ID: 277276 [Multi-domain] Cd Length: 83 Bit Score: 46.73 E-value: 1.34e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCD----ECS------------------HDRRAVPSRGWDHPVRVCFN 755
Cdd:cd15737    2 WEDDSSVTHCPICLRSFGLLLRKHHCRLCGKVVCDdrrtKCStevpldllssalpdlpfvFKEPQSDIPDDTKSVRVCRD 81


                 .
gi 528524508 756 C 756
Cdd:cd15737   82 C 82

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.

Pssm-ID: 277281 [Multi-domain] Cd Length: 67 Bit Score: 45.70 E-value: 1.88e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528524508 699 VPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGwDHPVRVCFNC 756
Cdd:cd15742    4 VPVSHVMMCMNCGSDFTLTLRRHHCHACGKIVCRNCSRNKYPLKYLK-DRPAKVCDGC 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).

Pssm-ID: 277283 [Multi-domain] Cd Length: 52 Bit Score: 44.72 E-value: 2.81e-06

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 528524508 602 TKHHCRACGEGFCDSCSSKTRPVPERgwGPAPVRVCDNCY 641
Cdd:cd15744   15 PKHNCYNCGGTFCDACSSNELPLPSS--IYEPARVCDVCY 52

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.

Pssm-ID: 277284 [Multi-domain] Cd Length: 52 Bit Score: 44.42 E-value: 4.41e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528524508 706 HCHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNCN 757
Cdd:cd15745    1 ACAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDLVLSVPDTCIYLRVCKTCY 52

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.

Pssm-ID: 277277 [Multi-domain] Cd Length: 61 Bit Score: 44.63 E-value: 4.89e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528524508 581 WRPNSQILSCNkCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPergwGP---APVRVCDNCY 641
Cdd:cd15738    3 WKSFRNVTECS-CSTPFDHFSKKHHCWRCGNVFCTRCIDKQRALP----GHlsqRPVPVCRACY 61

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.

Pssm-ID: 277293 [Multi-domain] Cd Length: 64 Bit Score: 44.56 E-value: 5.84e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 581 WRPNSQILSCNKCA-TSFKDNDTKHHCRACGEGFCDSCSSKTRPVPErgWGPAPVRVCDNCY 641
Cdd:cd15754    2 WIPDKATDICMRCTqTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPR--LSPKPVRVCSLCY 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.

Pssm-ID: 277280 [Multi-domain] Cd Length: 65 Bit Score: 44.01 E-value: 9.01e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 698 WVPDHEILHCHNCRKEF-SIKLSKHHCRACGQGFCDECSHDRRAVPSRGwDHPVRVCFNC 756
Cdd:cd15741    3 WVRDNEVTMCMRCKEPFnALTRRRHHCRACGYVVCWKCSDYKATLEYDG-NKLNRVCKHC 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.

Pssm-ID: 277275 [Multi-domain] Cd Length: 56 Bit Score: 43.33 E-value: 1.10e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 528524508 590 CNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGP---APVRVCDNCY 641
Cdd:cd15736    2 CHTCSRTFNLNIRAHHCRKCGKLFCRRHLPNMIPLNLSAYDPrngKWYRCCHSCF 56

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.

Pssm-ID: 277296 [Multi-domain] Cd Length: 70 Bit Score: 43.13 E-value: 1.86e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528524508 589 SCNKCATSFKDN-----DTK------HHCRACGEGFCDSCSSKTRPVPERGWgPAPVRVCDNCY 641
Cdd:cd15757    8 SCQKCDQPFFWNfkqmwDSKkiglrqHHCRKCGKAVCGKCSSKRSTIPLMGF-EFEVRVCDSCH 70

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).

Pssm-ID: 277283 [Multi-domain] Cd Length: 52 Bit Score: 42.40 E-value: 1.87e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 528524508 707 CHNCRKE-FSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDhPVRVCFNC 756
Cdd:cd15744    2 CSLCQEDfASLALPKHNCYNCGGTFCDACSSNELPLPSSIYE-PARVCDVC 51

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.

Pssm-ID: 277281 [Multi-domain] Cd Length: 67 Bit Score: 43.00 E-value: 2.25e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 583 PNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVpeRGWGPAPVRVCDNCY 641
Cdd:cd15742    5 PVSHVMMCMNCGSDFTLTLRRHHCHACGKIVCRNCSRNKYPL--KYLKDRPAKVCDGCF 61

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).

Pssm-ID: 277256 [Multi-domain] Cd Length: 61 Bit Score: 41.95 E-value: 3.88e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSktrpvpergWGPAPVRVCDNCY 641
Cdd:cd15716    4 WVNDSDVPFCPDCGKKFNLARRRHHCRLCGSIMCNKCSQ---------FLPLHIRCCHHCK 55

FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ZFY19, also termed mixed lineage leukemia (MLL) partner containing FYVE domain, is encoded by a novel gene, MLL partner containing FYVE domain (MPFYVE). The FYVE domain of ZFY19 resembles FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the 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. The biological function of ZFY19 remains unclear.

Pssm-ID: 277288 [Multi-domain] Cd Length: 51 Bit Score: 40.57 E-value: 9.03e-05

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 528524508 589 SCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGWGPApvRVCDNCY 641
Cdd:cd15749    1 RCFGCAAKFSLFKKECGCKNCGRSFCKGCLTFSAVVPRKGNQKQ--KVCKQCH 51

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.

Pssm-ID: 277300 Cd Length: 76 Bit Score: 40.72 E-value: 1.36e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528524508 698 WVPDHEILHCHNCRKEFSIKLSKHHCRACGQGFCDEcsHDRRAV---------PSRG-WdhpVRVCFNC-NKKPG 761
Cdd:cd15761    4 WKKPSGKSRCSECGKTLNKKNGIVNCRKCGELFCNE--HCRNRIklnnsaeydPKNGkW---CRCCEKCfTSRPG 73

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.

Pssm-ID: 277276 [Multi-domain] Cd Length: 83 Bit Score: 40.95 E-value: 1.72e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDS----CSSKTR-----------------PVPERGWGPAPVRVCDN 639
Cdd:cd15737    2 WEDDSSVTHCPICLRSFGLLLRKHHCRLCGKVVCDDrrtkCSTEVPldllssalpdlpfvfkePQSDIPDDTKSVRVCRD 81


                 .
gi 528524508 640 C 640
Cdd:cd15737   82 C 82

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.

Pssm-ID: 277300 Cd Length: 76 Bit Score: 40.33 E-value: 1.88e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDS-C------SSKTRPVPERG-WgpapVRVCDNCYEAR 644
Cdd:cd15761    4 WKKPSGKSRCSECGKTLNKKNGIVNCRKCGELFCNEhCrnriklNNSAEYDPKNGkW----CRCCEKCFTSR 71

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.

Pssm-ID: 277284 [Multi-domain] Cd Length: 52 Bit Score: 39.79 E-value: 1.92e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528524508 590 CNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPERGwGPAPVRVCDNCY 641
Cdd:cd15745    2 CAICAKAFSLFRRKYVCRLCGGVVCHSCSSEDLVLSVPD-TCIYLRVCKTCY 52

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.

Pssm-ID: 277277 [Multi-domain] Cd Length: 61 Bit Score: 39.62 E-value: 2.51e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 528524508 698 WVPDHEILHChNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWDHPVRVCFNC 756
Cdd:cd15738    3 WKSFRNVTEC-SCSTPFDHFSKKHHCWRCGNVFCTRCIDKQRALPGHLSQRPVPVCRAC 60

FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc finger FYVE domain-containing protein 27 (ZFY27 or ZFYVE27), is a FYVE domain-containing protein involved in transport of neuronal cargoes and implicated in the onset of hereditary spastic paraplegia (HSP). It is involved in neurite outgrowth through binding to spastin. Moreover, it functions as a key regulator of the Rab11-dependent membrane trafficking during neurite extension. It serves as an adaptor molecule that links its associated proteins, such as Rab11-GDP, VAP-A and -B, Surf4, and RTN3, to KIF5, a motor protein that mediates anterograde vesicular transport in neurons, and thus plays a key role in the maintenance of neuronal function. The FYVE domain of protrudin resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the 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. In addition, unlike canonical FYVE domains that is located to early endosomes and specifically binds to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), the FYVE domain of protrudin is located to plasma membrane and preferentially binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). In addition to FYVE-related domain, protrudin also contains a Rab11-binding domain (RBD11), two hydrophobic domains, HP-1 and HP-2, an FFAT motif, and a coiled-coil domain.

Pssm-ID: 277262 [Multi-domain] Cd Length: 62 Bit Score: 39.02 E-value: 4.56e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 707 CHNCRKEFSIKLSKHH-CRACGQGFCDECSHDRRAVPSRGWDHP------VRVCFNCNKK 759
Cdd:cd15723    2 CTGCGASFSVLLKKRRsCNNCGNAFCSRCCSKKVPRSVMGATAPaaqretVFVCSGCNDK 61

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.

Pssm-ID: 277265 [Multi-domain] Cd Length: 58 Bit Score: 38.69 E-value: 6.09e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528524508 581 WRPNSQILSCNKCATSFKDNDTKHHCRACGEGFCDSCSSKTRPVPErgwGPAPVRVCDNCY 641
Cdd:cd15726    1 WQDDTDVTHCLDCKSEFSWMVRRHHCRLCGRIFCYACSNFYVLTAH---GGKKERCCKACF 58

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.

Pssm-ID: 277275 [Multi-domain] Cd Length: 56 Bit Score: 37.93 E-value: 8.96e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 528524508 707 CHNCRKEFSIKLSKHHCRACGQGFCDECSHDRRAVPSRGWD----HPVRVCFNC 756
Cdd:cd15736    2 CHTCSRTFNLNIRAHHCRKCGKLFCRRHLPNMIPLNLSAYDprngKWYRCCHSC 55

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

Pssm-ID: 380815 [Multi-domain] Cd Length: 44 Bit Score: 36.32 E-value: 2.38e-03

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                 ....*....|....*....|....*....|....*....|....*.
gi 528524508  71 CDLCKglsghlpgvRQRAIVRCQTCKINLCLECQKRTHSGGNKRRH 116
Cdd:cd19757    2 CDECE---------EREATVYCLECEEFLCDDCSDAIHRRGKLTRS 38

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.

Pssm-ID: 277280 [Multi-domain] Cd Length: 65 Bit Score: 36.31 E-value: 4.81e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528524508 581 WRPNSQILSCNKCATSFKD-NDTKHHCRACGEGFCDSCSSKTRPVPERgwGPAPVRVCDNCY 641
Cdd:cd15741    3 WVRDNEVTMCMRCKEPFNAlTRRRHHCRACGYVVCWKCSDYKATLEYD--GNKLNRVCKHCY 62

Translocon at the Outer-envelope membrane of Chloroplasts 34-like (Toc34-like); The Toc34-like (Translocon at the Outer-envelope membrane of Chloroplasts) family contains several Toc proteins, including Toc34, Toc33, Toc120, Toc159, Toc86, Toc125, and Toc90. The Toc complex at the outer envelope membrane of chloroplasts is a molecular machine of ~500 kDa that contains a single Toc159 protein, four Toc75 molecules, and four or five copies of Toc34. Toc64 and Toc12 are associated with the translocon, but do not appear to be part of the core complex. The Toc translocon initiates the import of nuclear-encoded preproteins from the cytosol into the organelle. Toc34 and Toc159 are both GTPases, while Toc75 is a beta-barrel integral membrane protein. Toc159 is equally distributed between a soluble cytoplasmic form and a membrane-inserted form, suggesting that assembly of the Toc complex is dynamic. Toc34 and Toc75 act sequentially to mediate docking and insertion of Toc159 resulting in assembly of the functional translocon.

Pssm-ID: 206652 Cd Length: 248 Bit Score: 39.22 E-value: 5.90e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 187 GNTGDGKSHTLNHTFfyGREVFKTSPTQESCT-----VGVWAAYdpvhKVAVIDTEGLLGAT---VN---LSQRTRLLLK 255
Cdd:cd01853   38 GKTGVGKSSTINSIF--GERKVSVSAFQSETLrprevSRTVDGF----KLNIIDTPGLLESQdqrVNrkiLSIIKRFLKK 111

                         90
                 ....*....|....*..
gi 528524508 256 VLAisDLVIYrthADRL 272
Cdd:cd01853  112 KTI--DVVLY---VDRL 123

FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc finger FYVE domain-containing protein 27 (ZFY27 or ZFYVE27), is a FYVE domain-containing protein involved in transport of neuronal cargoes and implicated in the onset of hereditary spastic paraplegia (HSP). It is involved in neurite outgrowth through binding to spastin. Moreover, it functions as a key regulator of the Rab11-dependent membrane trafficking during neurite extension. It serves as an adaptor molecule that links its associated proteins, such as Rab11-GDP, VAP-A and -B, Surf4, and RTN3, to KIF5, a motor protein that mediates anterograde vesicular transport in neurons, and thus plays a key role in the maintenance of neuronal function. The FYVE domain of protrudin resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the 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. In addition, unlike canonical FYVE domains that is located to early endosomes and specifically binds to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), the FYVE domain of protrudin is located to plasma membrane and preferentially binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). In addition to FYVE-related domain, protrudin also contains a Rab11-binding domain (RBD11), two hydrophobic domains, HP-1 and HP-2, an FFAT motif, and a coiled-coil domain.

Pssm-ID: 277262 [Multi-domain] Cd Length: 62 Bit Score: 35.55 E-value: 6.83e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528524508 589 SCNKCATSFKDNDTKHH-CRACGEGFCDSCSSKtRPVPERGWGPAP------VRVCDNCY 641
Cdd:cd15723    1 NCTGCGASFSVLLKKRRsCNNCGNAFCSRCCSK-KVPRSVMGATAPaaqretVFVCSGCN 59

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

Pssm-ID: 206648 [Multi-domain] Cd Length: 161 Bit Score: 37.82 E-value: 8.25e-03

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gi 528524508 185 IFGNTGDGKSHTLNHtfFYGREVFKTSPTQES---CTVGVWAAYDPVHKVAVIDTEGLLGAtvNLSQRTRLLLKVLAISD 261
Cdd:cd00882    2 VVGRGGVGKSSLLNA--LLGGEVGEVSDVPGTtrdPDVYVKELDKGKVKLVLVDTPGLDEF--GGLGREELARLLLRGAD 77


                 ....
gi 528524508 262 LVIY 265
Cdd:cd00882   78 LILL 81

B-box-type 2 zinc finger found in Myc-binding protein 2 (MYCBP2) and similar proteins; MYCBP2, also termed protein associated with Myc (Pam), is an atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues. MYCBP2 harbors a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

Pssm-ID: 380857 Cd Length: 50 Bit Score: 35.06 E-value: 9.10e-03

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gi 528524508  26 GTDEAIFECDECCSLQCLRCEEELHRQERLRNHERIRLKP 65
Cdd:cd19799    9 GETAAIIFCCDCGNYLCAECDRFLHLHRKNRSHQRQVFKE 48