DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) PIKfyve-like proteins. PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain. PIKfyve-like proteins are important phosphatidylinositol (3)-monophosphate (PtdIns(3)P)-5-kinases, producing PtdIns(3,5)P2, which plays a major role in multivesicular body (MVB) sorting and control of retrograde traffic from the vacuole back to the endosome and/or Golgi. PIKfyve itself has been shown to be play a role in regulating early-endosome-to-trans-Golgi network (TGN) retrograde trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  369 DLWKKICHHSSGMEFQDHRYWLRTHPNCIVGKELVNWLIRNGHIATRAQAIAIGQAMVDGRWLDCVSHHDqLFRDEYALY 448
Cdd:cd04448     1 DLWEKICRSSTGIEFQDHRYRLRTYTNCILGKELVNWLIRQGKAATRVQAIAIGQALLDAGWIECVSDDD-LFRDEYALY 79

                  ..
gi 767917177  449 RP 450
Cdd:cd04448    80 KP 81

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) PIKfyve-like proteins. PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain. PIKfyve-like proteins are important phosphatidylinositol (3)-monophosphate (PtdIns(3)P)-5-kinases, producing PtdIns(3,5)P2, which plays a major role in multivesicular body (MVB) sorting and control of retrograde traffic from the vacuole back to the endosome and/or Golgi. PIKfyve itself has been shown to be play a role in regulating early-endosome-to-trans-Golgi network (TGN) retrograde trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  369 DLWKKICHHSSGMEFQDHRYWLRTHPNCIVGKELVNWLIRNGHIATRAQAIAIGQAMVDGRWLDCVSHHDqLFRDEYALY 448
Cdd:cd04448     1 DLWEKICRSSTGIEFQDHRYRLRTYTNCILGKELVNWLIRQGKAATRVQAIAIGQALLDAGWIECVSDDD-LFRDEYALY 79

                  ..
gi 767917177  449 RP 450
Cdd:cd04448    80 KP 81

TCP-1/cpn60 chaperonin family; This family includes members from the HSP60 chaperone family and the TCP-1 (T-complex protein) family.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   645 WRDIIVSLVCQVVQTVRPDVKNQDDDMdirqfVHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIE 724
Cdd:pfam00118  137 ESDFLAKLVVDAVLAIPKNDGSFDLGN-----IGVVKILGGSLEDSELVDGVVLDKGPLHPDMPKRLENAKVLLLNCSLE 211

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   725 YlYREETK--FTCIDP-----IVLQEREFLKNYVQRIVDVRPTLVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISR 797
Cdd:pfam00118  212 Y-EKTETKatVVLSDAeqlerFLKAEEEQILEIVEKIIDSGVNVVVCQKGIDDLALHFLAKNGIMALRRVKKRDLERLAK 290

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767917177   798 MTQGDLVMSMDQlLTKPHLGTCHKFYMQIFqlpneQTKTLMFFEGCPQHLGCTIKLRGGSDYELARVKEIL 868
Cdd:pfam00118  291 ATGARAVSSLDD-LTPDDLGTAGKVEEEKI-----GDEKYTFIEGCKSPKAATILLRGATDHVLDEIERSI 355

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767917177   166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPG-KFMGYTGDLRACTYC 225
Cdd:pfam01363    2 VWVPDSSATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLlPELGSNKPVRVCDAC 62

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177    166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:smart00064    3 HWIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIERPVRVCDDC 62

thermosome subunit beta;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  647 DIIVSLVCQVVQTVrpDVKNQDDDMDIRqfvhIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIEYL 726
Cdd:NF041083  170 EIAVKAVKQVAEKR--DGKYYVDLDNIQ----IEKKHGGSIEDTQLIYGIVIDKEVVHPGMPKRVENAKIALLDAPLEVK 243

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  727 YRE-ETKFTCIDPIVL-----QEREFLKNYVQRIVDVRPTLVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISRMTQ 800
Cdd:NF041083  244 KTEiDAEIRITDPDQLqkfldQEEKMLKEMVDKIKATGANVVFCQKGIDDLAQHYLAKAGILAVRRVKKSDMEKLAKATG 323

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767917177  801 GDLVMSMDQLlTKPHLGTCHKFymqifqlpnEQTKT----LMFFEGCPQHLGCTIKLRGGSD 858
Cdd:NF041083  324 ARIVTNIDDL-TPEDLGYAELV---------EERKVgddkMVFVEGCKNPKAVTILIRGGTE 375

chaperonin_like superfamily. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I is seven-fold and they are found in eubacteria (GroEL) and in organelles of eubacterial descent (hsp60 and RBP). The symmetry of type II is eight- or nine-fold and they are found in archea (thermosome), thermophilic bacteria (TF55) and in the eukaryotic cytosol (CTT). Their common function is to sequester nonnative proteins inside their central cavity and promote folding by using energy derived from ATP hydrolysis. This superfamily also contains related domains from Fab1-like phosphatidylinositol 3-phosphate (PtdIns3P) 5-kinases that only contain the intermediate and apical domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  645 WRDIIVSLVCQVVQTVRPDVKNQDDDMdirqfVHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIE 724
Cdd:cd03333    19 WDDFLGKLVVDAVLKVGPDNRMDDLGV-----IKVEKIPGGSLEDSELVVGVVFDKGYASPYMPKRLENAKILLLDCPLE 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  725 YLyreetkftcidpivlqereflknyvqrivdvrptlVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISRMTQGDLV 804
Cdd:cd03333    94 YV-----------------------------------VIAEKGIDDLALHYLAKAGIMAVRRVKKEDLERIARATGATIV 138

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767917177  805 MSMDQLlTKPHLGTCHKFYMQIFQlpneqTKTLMFFEGCPQHLGCTIKLRGGSDYELARVKEILIFMICVAYHSQLE 881
Cdd:cd03333   139 SSLEDL-TPEDLGTAELVEETKIG-----EEKLTFIEGCKGGKAATILLRGATEVELDEVKRSLHDALCAVRAAVEE 209

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767917177  166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYCRK 227
Cdd:cd15725     1 YWMPDSSCKECYECSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFIGYPGDLRVCTYCCK 62

T-complex protein 1, gamma subunit; Members of this family, all eukaryotic, are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1) or TRiC. The archaeal equivalent group II chaperonin is often called the thermosome. Both are somewhat related to the group I chaperonin of bacterial, GroEL/GroES. This family consists exclusively of the CCT gamma chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   645 WRDIIVSLVCQVVQTVRPDvKNQDDDMDIRQFVHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIE 724
Cdd:TIGR02344  163 WSDLMCDLALDAVRTVQRD-ENGRKEIDIKRYAKVEKIPGGDIEDSCVLKGVMINKDVTHPKMRRYIENPRIVLLDCPLE 241

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   725 YLYRE---------ETKFTcidPIVLQEREFLKNYVQRIVDVRPTLVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERI 795
Cdd:TIGR02344  242 YKKGEsqtnieitkEEDWN---RILQMEEEYVQLMCEDIIAVKPDLVITEKGVSDLAQHYLLKANITAIRRVRKTDNNRI 318

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767917177   796 SRMTQGDLVMSMDQlLTKPHLGT-CHKFYMQIFqlpneQTKTLMFFEGCPQHLGCTIKLRGGSdyelarvKEIL 868
Cdd:TIGR02344  319 ARACGATIVNRPEE-LRESDVGTgCGLFEVKKI-----GDEYFTFITECKDPKACTILLRGAS-------KDIL 379

chaperonin families, type I and type II. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I is seven-fold and they are found in eubacteria (GroEL) and in organelles of eubacterial descent (hsp60 and RBP). The symmetry of type II is eight- or nine-fold and they are found in archea (thermosome), thermophilic bacteria (TF55) and in the eukaryotic cytosol (CTT). Their common function is to sequester nonnative proteins inside their central cavity and promote folding by using energy derived from ATP hydrolysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  645 WRDIIVSLVCQVVQTVRPDVKNQDDDMdirqfVHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIE 724
Cdd:cd00309   155 GDDFLGELVVDAVLKVGKENGDVDLGV-----IRVEKKKGGSLEDSELVVGMVFDKGYLSPYMPKRLENAKILLLDCKLE 229

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  725 YLyreetkftcidpivlqereflknyvqrivdvrptlVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISRMTQGDLV 804
Cdd:cd00309   230 YV-----------------------------------VIAEKGIDDEALHYLAKLGIMAVRRVRKEDLERIAKATGATIV 274

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767917177  805 MSMDQLlTKPHLGTCHKFYMQIFqlpNEQTKTlmFFEGCPQHLGCTIKLRGGSDYELARVK 865
Cdd:cd00309   275 SRLEDL-TPEDLGTAGLVEETKI---GDEKYT--FIEGCKGGKVATILLRGATEVELDEAE 329

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767917177   166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPG-KFMGYTGDLRACTYC 225
Cdd:pfam01363    2 VWVPDSSATVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLlPELGSNKPVRVCDAC 62

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177    166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:smart00064    3 HWIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLGIERPVRVCDDC 62

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   380 GMEFQDHRYWLRTHPNCIVGKELVNWLIRNGHIATRAQAIAIGQAMVDGRWLDCVSHHDQLFRDEYALYR 449
Cdd:pfam00610    1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHGLFKDSYYFYR 70

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 767917177  167 WMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:cd15731     5 WVPDEACPQCMACSAPFTVLRRRHHCRNCGKIFCSRCSSNSVPLPRYGQMKPVRVCNHC 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767917177  175 ECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:cd00065     1 RCMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSFGSGKPVRVCDSC 51

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767917177  167 WMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRcCNQEIPGKfmgytgdLRACTYCRKI 228
Cdd:cd15716     4 WVNDSDVPFCPDCGKKFNLARRRHHCRLCGSIMCNK-CSQFLPLH-------IRCCHHCKDL 57

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:cd15734     1 YWVPDSEIKECSVCKRPFSPRLSKHHCRACGQGVCDDCSKNRRPVPSRGWDHPVRVCDPC 60

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 767917177  167 WMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIP 209
Cdd:cd15733     1 WVPDHAASHCFGCDCEFWLAKRKHHCRNCGNVFCADCSNYKLP 43

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  167 WMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCS----RCCN-----------QEIPGKFMGYTGD-------LRACTY 224
Cdd:cd15737     2 WEDDSSVTHCPICLRSFGLLLRKHHCRLCGKVVCDdrrtKCSTevpldllssalPDLPFVFKEPQSDipddtksVRVCRD 81

                  ..
gi 767917177  225 CR 226
Cdd:cd15737    82 CK 83

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  166 YWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYC 225
Cdd:cd15732     1 RWVPDHLAASCYGCEREFWLASRKHHCRNCGNVFCGSCCNQKLPVPSQQLFEPSRVCKSC 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767917177  175 ECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQE--IPgKFmGYTGDLRACTYC 225
Cdd:cd15720     7 ECHRCRVQFGVFQRKHHCRACGQVFCGKCSSKSstIP-KF-GIEKEVRVCDPC 57

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767917177  167 WMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIpgKFMGYTGDLRACTYCRKIAL 230
Cdd:cd15758     6 WLKDDEATHCKQCEKEFSISRRKHHCRNCGHIFCNTCSSNEL--ALPSYPKPVRVCDSCHTLLL 67

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by cyclic AMP, a second messenger that plays a role in the control of diverse cellular processes, such as cell adhesion and insulin secretion. Epac-like proteins share a common domain architecture, containing RasGEF, DEP and CAP-effector (cAMP binding) domains. The DEP domain is involved in membrane localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177  385 DHRYWLRTHPNCIVGKELVNWLIRNGH-IATRAQAIAIGQAMVDGRWLDCVSHHDQlFRDEYALYRplqsteFSEtpspD 463
Cdd:cd04437    19 DRKYHLRTYRQCCVGTELVDWLLQQSPcVQSRSQAVGMWQVLLEEGVLLHVDQELH-FQDKYQFYR------FSD----D 87

                          90       100
                  ....*....|....*....|..
gi 767917177  464 SDSVNSVEGH-SEPSWFKDIKF 484
Cdd:cd04437    88 ECSPAPLEKReAEEELQEAVTL 109

T-complex protein 1, alpha subunit; Members of this family, all eukaryotic, are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1) or TRiC. The archaeal equivalent group II chaperonin is often called the thermosome. Both are somewhat related to the group I chaperonin of bacterial, GroEL/GroES. This family consists exclusively of the CCT alpha chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   677 VHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIE-YLYREETKFTCIDP-----IVLQEREFLKNY 750
Cdd:TIGR02340  191 INILKAHGKSARESMLVKGYALNCTVASQQMPKRIKNAKIACLDFNLQkAKMALGVQIVVDDPekleqIRQREADITKER 270

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767917177   751 VQRIVDVRPTLVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISRMTQGDLVMSM-----DQLLTKPHLGTCHKFYMQ 825
Cdd:TIGR02340  271 IKKILDAGANVVLTTGGIDDMCLKYFVEAGAMGVRRCKKEDLKRIAKATGATLVSTLadlegEETFEASYLGFADEVVQE 350

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 767917177   826 ifQLPNEQtktLMFFEGCPQHLGCTIKLRGGSDYELARVKEILIFMICV 874
Cdd:TIGR02340  351 --RIADDE---CILIKGTKKRKSASIILRGANDFMLDEMERSLHDALCV 394

T-complex protein 1, epsilon subunit; Members of this family, all eukaryotic, are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1) or TRiC. The archaeal equivalent group II chaperonin is often called the thermosome. Both are somewhat related to the group I chaperonin of bacterial, GroEL/GroES. This family consists exclusively of the CCT epsilon chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.