cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  358 EVTVLFINL-GFSEedLAKMLDSKGLQK-LQDAFALVQKCIYEYEGTINKFLvddkGSTVIAAFGLPpVTHENDPVRGIL 435
Cdd:cd07302      1 EVTVLFADIvGFTA--LSERLGPEELVElLNEYFSAFDEIIERHGGTVDKTI----GDAVMAVFGLP-GAHEDHAERAVR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  436 ASLAICAALGKL--------GLKASVGITSGAALCGVVGHQgnRREYTVLGDIVNLSARLMQKAKseRGGVITDESTKLY 507
Cdd:cd07302     74 AALEMQEALAELnaereggpPLRLRIGIHTGPVVAGVVGSE--RPEYTVIGDTVNLAARLESLAK--PGQILVSEATYEL 149

                          170       180
                   ....*....|....*....|....*...
gi 2429714559  508 AQDV-LHFEERPEIMVKGKNDSIKIHRP 534
Cdd:cd07302    150 LGDAgFEFEELGEVELKGKSGPVRVYRL 177

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
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2429714559 1079 SYCFHCYTKFAASKDKHRCKCCGYVFCTPCTPKACRKKLPGSTGDAVRHCCNCYA 1133
Cdd:pfam01363   10 TVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLLPELGSNKPVRVCDACYD 64

Predicted ATPase [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  920 LLLCALYAISRDRSTIFCLDNAMYMDEKSW-----ILTTIITKYFtncLVVIGTRPpsmalTENTQSSSFRKQLRVVKKM 994
Cdd:COG3899    421 ALLRLLRALAAERPLVLVLDDLHWADPASLellefLLRRLRDLPL---LLVGTYRP-----EEVPPAHPLRLLLAELRRA 492

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2429714559  995 NNTTCEVM-EPLENALIERLALQILKVRTIPGELMSILLSRSQGNALFLREIISEMIQQQVINVDSKRQTCTMQVQE 1070
Cdd:COG3899    493 GAGVTRLElGPLSREEVAALVADLLGAAELPAELAELLVERTGGNPFFLEELLRALLEEGLLRFDGGGWRWDAALAA 569

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  358 EVTVLFINL-GFSEedLAKMLDSKGLQK-LQDAFALVQKCIYEYEGTINKFLvddkGSTVIAAFGLPpVTHENDPVRGIL 435
Cdd:cd07302      1 EVTVLFADIvGFTA--LSERLGPEELVElLNEYFSAFDEIIERHGGTVDKTI----GDAVMAVFGLP-GAHEDHAERAVR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  436 ASLAICAALGKL--------GLKASVGITSGAALCGVVGHQgnRREYTVLGDIVNLSARLMQKAKseRGGVITDESTKLY 507
Cdd:cd07302     74 AALEMQEALAELnaereggpPLRLRIGIHTGPVVAGVVGSE--RPEYTVIGDTVNLAARLESLAK--PGQILVSEATYEL 149

                          170       180
                   ....*....|....*....|....*...
gi 2429714559  508 AQDV-LHFEERPEIMVKGKNDSIKIHRP 534
Cdd:cd07302    150 LGDAgFEFEELGEVELKGKSGPVRVYRL 177

Adenylate cyclase, class 3 [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559   93 RKELDVRLSAYLPAVVRRYLERQDQQRVPDTHETTVVSMFADVSGFTAMTESLaargpvGAEYLAKHLNSYFEQLLRLVS 172
Cdd:COG2114    188 RERLRDLLGRYLPPEVAERLLAGGEELRLGGERREVTVLFADIVGFTALSERL------GPEELVELLNRYFSAMVEIIE 261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  173 SSGGDVFKFAGDAMLIFWPEnkEDTLESLLRRSVQCALRIQEHLHK--AELAPGVVLSVKMGIGIggatiaHLG----GE 246
Cdd:COG2114    262 RHGGTVDKFIGDGVMAVFGA--PVAREDHAERAVRAALAMQEALAElnAELPAEGGPPLRVRIGI------HTGevvvGN 333

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2429714559  247 SdGSTARMEYVAVGPALEQAFNSEHQAEAGDVICSPEAWKLVHPFFDGEPVRSgtnfHKVKQVTVPVR 314
Cdd:COG2114    334 I-GSEDRLDYTVIGDTVNLAARLESLAKPGEILVSEATYDLLRDRFEFRELGE----VRLKGKAEPVE 396

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
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2429714559 1079 SYCFHCYTKFAASKDKHRCKCCGYVFCTPCTPKACRKKLPGSTGDAVRHCCNCYA 1133
Cdd:pfam01363   10 TVCMICSKPFTFFRRRHHCRNCGRVFCSACSSKKISLLPELGSNKPVRVCDACYD 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2429714559 1071 PWGEKCKTSYCFHCYTKFAASKDKHRCKCCGYVFCTPCtpkaCRKKLP---GSTGDAVRHCCNCY 1132
Cdd:cd15727      3 PWVPDKECPVCMSCKKKFDFFKRRHHCRRCGKCFCSDC----CSNKVPlprMCFVDPVRVCNECA 63

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 2429714559  1071 PWGEKCKTSYCFHCYTKFAASKDKHRCKCCGYVFCTPCTPKACRKKLPGsTGDAVRHCCNCYA 1133
Cdd:smart00064    3 HWIPDEEVSNCMGCGKEFNLTKRRHHCRNCGRIFCSKCSSKKAPLPKLG-IERPVRVCDDCYE 64

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  1485 HFKGWSNATMWKKRYAVLQNARLVLqYDEMNGSQPRRC-TSLFLKGAKVSPC-DPDVAAKVNCFQVEVNEWTKgkylinq 1562
Cdd:smart00233    8 YKKSGGGKKSWKKRYFVLFNSTLLY-YKSKKDKKSYKPkGSIDLSGCTVREApDPDSSKKPHCFEIKTSDRKT------- 79

                            90       100
                    ....*....|....*....|....*
gi 2429714559  1563 krfFVIGVESDAEVDHWVYMVKYAI 1587
Cdd:smart00233   80 ---LLLQAESEEEREKWVEALRKAI 101

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559    92 ARKELDVRLSAYLPAVVRRYLeRQDQQRVPDTHETTVVSMFADVSGFTAMTESLAargpvgAEYLAKHLNSYFEQLLRLV 171
Cdd:smart00044    2 EKKKTDRLLDQLLPASVAEQL-KRGGSPVPAESYDNVTILFSDIVGFTSLCSTST------PEQVVNLLNDLYSRFDQII 74

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559   172 SSSGGDVFKFAGDAMLIFWPeNKEDTLESLLRRSVQCALRIQEHLHKAE-LAPGVVLSVKMGIGIGGAtiahLGGEsDGS 250
Cdd:smart00044   75 DRHGGYKVKTIGDAYMVASG-LPEEALVDHAELIADEALDMVEELKTVLvQHREEGLRVRIGIHTGPV----VAGV-VGI 148

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|....*
gi 2429714559   251 TA-RMEYvaVGPALEQAFNSEHQAEAGDVICSPEAWKLVHPFFDG 294
Cdd:smart00044  149 RMpRYCL--FGDTVNLASRMESAGDPGQIQVSEETYSLLARRGGQ 191

Predicted ATPase [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559 1188 ALRPPRTVKSVLTTLLDQLTVSQRMIMKTASVVGPTFEEELLRGSCPikAHLAHFAQDIAELERLAMIRRIDTFIGGVps 1267
Cdd:COG3899    569 ALALPDTVVDLLAARLDRLPPAARRVLRLAAVLGRRFDLELLAAVLG--LSEAELAAALEELVAAGLLVPRGDAGGGR-- 644

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2429714559 1268 rpassndiklaaasstgsitcstphlkvkFEFNHGFMQDVIRGQMLSSQLDKLNARI 1324
Cdd:COG3899    645 -----------------------------YRFRHDLVREAAYASLPPEERRALHRRI 672

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  358 EVTVLFINL-GFSEedLAKMLDSKGLQK-LQDAFALVQKCIYEYEGTINKFLvddkGSTVIAAFGLPpVTHENDPVRGIL 435
Cdd:cd07302      1 EVTVLFADIvGFTA--LSERLGPEELVElLNEYFSAFDEIIERHGGTVDKTI----GDAVMAVFGLP-GAHEDHAERAVR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  436 ASLAICAALGKL--------GLKASVGITSGAALCGVVGHQgnRREYTVLGDIVNLSARLMQKAKseRGGVITDESTKLY 507
Cdd:cd07302     74 AALEMQEALAELnaereggpPLRLRIGIHTGPVVAGVVGSE--RPEYTVIGDTVNLAARLESLAK--PGQILVSEATYEL 149

                          170       180
                   ....*....|....*....|....*...
gi 2429714559  508 AQDV-LHFEERPEIMVKGKNDSIKIHRP 534
Cdd:cd07302    150 LGDAgFEFEELGEVELKGKSGPVRVYRL 177

Adenylate cyclase, class 3 [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559   93 RKELDVRLSAYLPAVVRRYLERQDQQRVPDTHETTVVSMFADVSGFTAMTESLaargpvGAEYLAKHLNSYFEQLLRLVS 172
Cdd:COG2114    188 RERLRDLLGRYLPPEVAERLLAGGEELRLGGERREVTVLFADIVGFTALSERL------GPEELVELLNRYFSAMVEIIE 261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  173 SSGGDVFKFAGDAMLIFWPEnkEDTLESLLRRSVQCALRIQEHLHK--AELAPGVVLSVKMGIGIggatiaHLG----GE 246
Cdd:COG2114    262 RHGGTVDKFIGDGVMAVFGA--PVAREDHAERAVRAALAMQEALAElnAELPAEGGPPLRVRIGI------HTGevvvGN 333

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2429714559  247 SdGSTARMEYVAVGPALEQAFNSEHQAEAGDVICSPEAWKLVHPFFDGEPVRSgtnfHKVKQVTVPVR 314
Cdd:COG2114    334 I-GSEDRLDYTVIGDTVNLAARLESLAKPGEILVSEATYDLLRDRFEFRELGE----VRLKGKAEPVE 396

Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse group of nucleotidyl cyclases (NC's) containing prokaryotic and eukaryotic proteins. They can be divided into two major groups; the mononucleotidyl cyclases (MNC's) and the diguanylate cyclases (DGC's). The MNC's, which include the adenylate cyclases (AC's) and the guanylate cyclases (GC's), have a conserved cyclase homology domain (CHD), while the DGC's have a conserved GGDEF domain, named after a conserved motif within this subgroup. Their products, cyclic guanylyl and adenylyl nucleotides, are second messengers that play important roles in eukaryotic signal transduction and prokaryotic sensory pathways.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  131 MFADVSGFTAMTESLaargpvGAEYLAKHLNSYFEQLLRLVSSSGGDVFKFAGDA-MLIFWPENkedtleslLRRSVQCA 209
Cdd:cd07556      5 LFADIVGFTSLADAL------GPDEGDELLNELAGRFDSLIRRSGDLKIKTIGDEfMVVSGLDH--------PAAAVAFA 70

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2429714559  210 LRIQEHLhkAELAPGVVLSVKMGIGiggatIAHLGGESDGSTARMEYVAVGPALEQAFNSEHQAEAGDV 278
Cdd:cd07556     71 EDMREAV--SALNQSEGNPVRVRIG-----IHTGPVVVGVIGSRPQYDVWGALVNLASRMESQAKAGQV 132

Adenylate and Guanylate cyclase catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  355 ELREVTVLFINL----GFSEEDLAKMLdskgLQKLQDAFALVQKCIYEYEGTINKFLvddkGSTVIAAFGLPpvthENDP 430
Cdd:pfam00211    5 PYDNVTILFADIvgftALSSRHSPEQV----VRLLNELYTRFDRLLDKHKVYKVKTI----GDAYMVVSGLP----EPSP 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559  431 ---VRGILASLAICAALG------KLGLKASVGITSGAALCGVVGHQgnRREYTVLGDIVNLSARLMQKAKSerGGVITD 501
Cdd:pfam00211   73 ahaRKIAEMALDMLEAIGevnvesSEGLRVRVGIHTGPVVAGVIGAR--MPRYDLWGNTVNLASRMESTGVP--GKIHVS 148

                          170       180
                   ....*....|....*....|....*
gi 2429714559  502 ESTKLYAQDVL-HFEERPEIMVKGK 525
Cdd:pfam00211  149 EETYRLLKTEGfEFTERGEIEVKGK 173

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 2429714559 1081 CFHCYTKFAASKDKHRCKCCGYVFCTPCTPKACRKKLPGStGDAVRHCCNCY 1132
Cdd:cd00065      2 CMLCGKKFSLFRRRHHCRRCGRVFCSKCSSKKLPLPSFGS-GKPVRVCDSCY 52

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559   349 DEFWGSELREVTVLFINL-GFSE--EDLAKMLDSKGLQKLQDAFalvQKCIYEYEGTINKFLvddkGSTVIAAFGLPPVT 425
Cdd:smart00044   27 SPVPAESYDNVTILFSDIvGFTSlcSTSTPEQVVNLLNDLYSRF---DQIIDRHGGYKVKTI----GDAYMVASGLPEEA 99

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2429714559   426 HENDPVRGILASLAICAALGKL-------GLKASVGITSGAALCGVVGHqgNRREYTVLGDIVNLSARLMQKAK 492
Cdd:smart00044  100 LVDHAELIADEALDMVEELKTVlvqhreeGLRVRIGIHTGPVVAGVVGI--RMPRYCLFGDTVNLASRMESAGD 171

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2429714559 1072 WGEKCKTSYCFHCY-TKFAASKDKHRCKCCGYVFCTPCTPKacRKKLPGSTGDAVRHCCNCYAL 1134
Cdd:cd15755      2 WVPDSEATVCMRCQkAKFTPVNRRHHCRKCGFVVCGPCSEK--KFLLPSQSSKPVRVCDFCYDL 63

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2429714559 1491 NATMWKKRYAVLQNARLVLQYDEMNGSQPRRCTSLFLKGAKV-SPCDPDVAAKVNCFQVEVNEWtkgkyliNQKRFFVIG 1569
Cdd:pfam00169   14 KKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVvEVVASDSPKRKFCFELRTGER-------TGKRTYLLQ 86

                           90
                   ....*....|....*....
gi 2429714559 1570 VESDAEVDHWVYMVKYAIE 1588
Cdd:pfam00169   87 AESEEERKDWIKAIQSAIR 105

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2429714559 1072 WGEKCKTSYCFHCYTKFAASKDKHRCKCCGYVFCTPCTPKacRKKLPgSTGDAVRHCCNCY 1132
Cdd:cd15721      1 WADDKEVTHCQQCEKEFSLSRRKHHCRNCGGIFCNSCSDN--TMPLP-SSAKPVRVCDTCY 58

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.

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gi 2429714559 1074 EKCKTsyCFHCYTKFAASKDKHRCKCCGYVFCTPCtpkaCRKKLPGS----TGDaVRHCCNCY 1132
Cdd:cd15725      6 SSCKE--CYECSEKFTTFRRRHHCRLCGQIFCSRC----CNQEIPGKfigyPGD-LRVCTYCC 61

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.

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gi 2429714559 1071 PWGEKCKTSYCFHCYTKFAASKDKHRCKCCGYVFCTPCTPKACRkkLPGSTgDAVRHCCNCY 1132
Cdd:cd15730      2 KWADDEEVQNCMACGKGFSVTVRKHHCRQCGNIFCNECSSKTAT--TPSSK-KPVRVCDACF 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.

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gi 2429714559 1081 CFHCYTKFAA-SKDKHRCKCCGYVFCTPCTPKACRKKLPGSTGDA-----VRHCCNCY 1132
Cdd:cd15723      2 CTGCGASFSVlLKKRRSCNNCGNAFCSRCCSKKVPRSVMGATAPAaqretVFVCSGCN 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.

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gi 2429714559 1081 CFHCYTKFAASKDKHRCKCCGYVFCTPCtpkaC--RKKLPGSTGDAVRHCCNCYAL 1134
Cdd:cd15729     16 CMQCEVKFTFTKRRHHCRACGKVLCSAC----CslKARLEYLDNKEARVCVPCYQT 67

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.

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gi 2429714559 1072 WGEKCKTSYCFHCYTKFAASKDKHRCKCCGYVFCTPCTpkACRKKLP--GSTGdAVRHCCNCY 1132
Cdd:cd15731      5 WVPDEACPQCMACSAPFTVLRRRHHCRNCGKIFCSRCS--SNSVPLPryGQMK-PVRVCNHCF 64

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.

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gi 2429714559 1071 PWGEKCKTSYCFHC-YTKFAASKDKHRCKCCGYVFCTPCTPKacRKKLPGSTGDAVRHCCNCY 1132
Cdd:cd15754      1 PWIPDKATDICMRCtQTNFSLLTRRHHCRKCGFVVCHECSRQ--RFLIPRLSPKPVRVCSLCY 61

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.

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gi 2429714559 1081 CFHCYTKFAASKDKHRCKCCGYVFCTPCtpkaCRKKLPGSTGDAV---RHCCNCY 1132
Cdd:cd15732     11 CYGCEREFWLASRKHHCRNCGNVFCGSC----CNQKLPVPSQQLFepsRVCKSCF 61