SNARE motif of VAM7; Fungal VAM7 (vacuolar morphogenesis protein 7) is a member of the Qc subfamily of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein family involved in vacuolar protein transport and membrane fusion. SNARE proteins consist of coiled-coil helices (called SNARE motifs) which mediate the interactions between SNARE proteins, and a transmembrane domain. The SNARE complex mediates membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qc-, as well as Qa- and Qb-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle. Their SNARE motifs form twisted and parallel heterotetrameric helix bundles.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1607550604 411 MGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDRV 456
Cdd:cd15858     1 MQEQDQQLEQLRKIVQRQKELGLAINQELEEQNELLDELDEDVDRT 46

SNARE motif of VAM7; Fungal VAM7 (vacuolar morphogenesis protein 7) is a member of the Qc subfamily of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein family involved in vacuolar protein transport and membrane fusion. SNARE proteins consist of coiled-coil helices (called SNARE motifs) which mediate the interactions between SNARE proteins, and a transmembrane domain. The SNARE complex mediates membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qc-, as well as Qa- and Qb-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle. Their SNARE motifs form twisted and parallel heterotetrameric helix bundles.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1607550604 411 MGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDRV 456
Cdd:cd15858     1 MQEQDQQLEQLRKIVQRQKELGLAINQELEEQNELLDELDEDVDRT 46

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1607550604 114 LRSFVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWFKSTvsNPDLTESRRRGLETYLRAIAESP 179
Cdd:pfam00787   6 LEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY--NEEFIEKRRKGLEQYLQRLLQHP 69

Helical region found in SNAREs; All alpha-helical motifs that form twisted and parallel four-helix bundles in target soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor proteins. This motif found in "Q-SNAREs".

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1607550604  407 QRRMMGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDR 455
Cdd:smart00397   3 ALAREEERDEELEQLEKSIQELKQIFLDMGTELEEQGEQLDRIEDNVDD 51

SNARE motif of VAM7; Fungal VAM7 (vacuolar morphogenesis protein 7) is a member of the Qc subfamily of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein family involved in vacuolar protein transport and membrane fusion. SNARE proteins consist of coiled-coil helices (called SNARE motifs) which mediate the interactions between SNARE proteins, and a transmembrane domain. The SNARE complex mediates membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qc-, as well as Qa- and Qb-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle. Their SNARE motifs form twisted and parallel heterotetrameric helix bundles.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1607550604 411 MGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDRV 456
Cdd:cd15858     1 MQEQDQQLEQLRKIVQRQKELGLAINQELEEQNELLDELDEDVDRT 46

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  103 YTLYNIALRLPLRSFVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWF-KSTVSNPDLTESRRRGLETYLRAIAESPDR 181
Cdd:smart00312  14 YYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFgRLNNFSEEFIEKRRRGLEKYLQSLLNHPEL 93

                           90
                   ....*....|...
gi 1607550604  182 RwRDVPAWRAFLN 194
Cdd:smart00312  94 I-NHSEVVLEFLE 105

SNARE motif of SYN8; Fungal SYN8 is a member of the Qc subfamily of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein family presetn in the endosomes. SNARE proteins consist of coiled-coil helices (called SNARE motifs) which mediate the interactions between SNARE proteins, and a transmembrane domain. The SNARE complex mediates membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qc-, as well as Qa- and Qb-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle. Their SNARE motifs form twisted and parallel heterotetrameric helix bundles.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1607550604 411 MGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDR 455
Cdd:cd15859     1 LLEQDEHLDHLSASIRRQHELSLQINDELDEQNELLDDLENGVDR 45

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604 101 KPYTLYNIALRLPL-----RSFVVQKRYSDFTALHNALTS-HVGSPPPaPLPAKSWFKSTVSNPDLTESRRRGLETYLRA 174
Cdd:cd06859    16 SAYVVYRVTTKTNLpdfkkSEFSVLRRYSDFLWLYERLVEkYPGRIVP-PPPEKQAVGRFKVKFEFIEKRRAALERFLRR 94

                          90
                  ....*....|....*....
gi 1607550604 175 IAESPdrRWRDVPAWRAFL 193
Cdd:cd06859    95 IAAHP--VLRKDPDFRLFL 111

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  65 PASHHITEQkgtsILHIMappaeISIPST-ILSTGESKPYTLYNIALRLPLRSF--------VVQKRYSDFTALHNALTS 135
Cdd:COG5391   121 STSHTILDY----FISST-----VSNPQSlTLLVDSRDKHTSYEIITVTNLPSFqlresrplVVRRRYSDFESLHSILIK 191

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1607550604 136 HVGSPPPAPLPAKSWFKSTVSN---PDLTESRRRGLETYLRAIAESPD-RRWRDVPAWRAFLNL 195
Cdd:COG5391   192 LLPLCAIPPLPSKKSNSEYYGDrfsDEFIEERRQSLQNFLRRVSTHPLlSNYKNSKSWESHSTL 255

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604 101 KPYTLYNIALRLPL-----RSFVVQKRYSDFTALHNALTS-HVGS--PPPaplPAKSWFKSTvsNPDLTESRRRGLETYL 172
Cdd:cd06861    16 SAHTVYTVRTRTTSpnfevSSFSVLRRYRDFRWLYRQLQNnHPGVivPPP---PEKQSVGRF--DDNFVEQRRAALEKML 90

                          90       100
                  ....*....|....*....|.
gi 1607550604 173 RAIAESPdrRWRDVPAWRAFL 193
Cdd:cd06861    91 RKIANHP--VLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  85 PAEISIPS--TILSTGESkpYTLYNIAL--RLplrsfVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWFksTVSNPDL 160
Cdd:cd06886     3 SVPISIPDykHVEQNGEK--FVVYNIYMagRQ-----LCSRRYREFANLHQNLKKEFPDFQFPKLPGKWPF--SLSEQQL 73

                          90       100
                  ....*....|....*....|....
gi 1607550604 161 tESRRRGLETYL------RAIAES 178
Cdd:cd06886    74 -DARRRGLEQYLekvcsiRVIGES 96

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  86 AEISIPSTILSTGES--KPYTLYNIALRL-PLR--SFVVQKRYSDFTALHNALTSHVgsPPPA-----PLPAKS-WFKST 154
Cdd:cd07280     3 TDVNVGDYTIVGGDTggGAYVVWKITIETkDLIgsSIVAYKRYSEFVQLREALLDEF--PRHKrneipQLPPKVpWYDSR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1607550604 155 VS-NPDLTESRRRGLETYLRAIAESPDrrWRDVPAWRAFL 193
Cdd:cd07280    81 VNlNKAWLEKRRRGLQYFLNCVLLNPV--FGGSPVVKEFL 118

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  88 ISIPSTILSTGESKPYTLYNIALRLPLRSFVVQKRYSDFTALHNALTSH---VGS---PPpaplpakswfKSTVSNPDL- 160
Cdd:cd07277     3 VWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKfpvVRSfdfPP----------KKAIGNKDAk 72

                          90
                  ....*....|....*.
gi 1607550604 161 -TESRRRGLETYLRAI 175
Cdd:cd07277    73 fVEERRKRLQVYLRRV 88

SNARE motif of syntaxin 6; Syntaxin 6 forms a complex with syntaxin 16 (Qa), Vti1a (Qb) and VAMP4 (R-SNARE) and is involved in the regulation of recycling of early endosomes to the trans-Golgi network (TGN). Syntaxin 6 and its yeast homolog TLG1 are members of the Qc subgroup of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, which consist of coiled-coil helices (called SNARE motifs) that mediate the interactions between SNARE proteins, and a transmembrane domain. The SNARE complexes mediate membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qa-, as well as Qb- and Qc-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1607550604 411 MGEQDEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDRV 456
Cdd:cd15851     1 MREQDEQLDGVGGTVGNLREQAQLIGDELEEQAELLDDLDHEVDRT 46

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  84 PPAEISIPSTILSTGESKPYTLYNIALRLPLRSFVVQKRYSDFTALHNALTSHVgsppPA---PLPAKSWFKSTVSnPDL 160
Cdd:cd06870     1 SCPSVSIPSSDEDREKKKRFTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQF----PAsnlKIPGKRLFGNNFD-PDF 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1607550604 161 TESRRRGLETYLRAIAESPdrRWRDVPAWRAFLNL 195
Cdd:cd06870    76 IKQRRAGLDEFIQRLVSDP--KLLNHPDVRAFLQM 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  99 ESKPYTLYNIALRLPLRS-------FVVQKRYSDFTALHNALTS------HVGSPPpaPLPAKSWFKStvSNPDLTESRR 165
Cdd:cd06881    13 HKKGYTEYKITSKVFSRSvpedvseVVVWKRYSDFKKLHRELSRlhkqlyLSGSFP--PFPKGKYFGR--FDAAVIEERR 88

                          90
                  ....*....|....
gi 1607550604 166 RGLETYLRAIAESP 179
Cdd:cd06881    89 QAILELLDFVGNHP 102

The phosphoinositide binding Phox Homology domain of fungal Grd19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604 103 YTLYNIALRLPLRSF-----VVQKRYSDFTALHNALTSHVGSPPPAPLPAKSwFKSTVSNpDLTESRRRGLETYLRAIAE 177
Cdd:cd07295    19 FTDYEIVCRTNIPAFklrvsSVRRRYSDFEYFRDILERESPRVMIPPLPGKI-FTNRFSD-EVIEERRQGLETFLQSVAG 96

                  ..
gi 1607550604 178 SP 179
Cdd:cd07295    97 HP 98

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  98 GESKPYTLYNIALRLPLRSF-----VVQKRYSDFTALHNALTS-HVGSPPPaPLPAKSWFKS----TVSnPDLTESRRRG 167
Cdd:cd06863    14 GSSDTYISYLITTKTNLPSFsrkefKVRRRYSDFVFLHECLSNdFPACVVP-PLPDKHRLEYitgdRFS-PEFITRRAQS 91

                          90
                  ....*....|...
gi 1607550604 168 LETYLRAIAESPD 180
Cdd:cd06863    92 LQRFLRRISLHPV 104

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  88 ISIPSTILSTGESKPYTLYNIALRLPLRSFVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWFKStvSNPDLTESRRRG 167
Cdd:cd06874     3 ITIPRYVLRGQGKDEHFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGN--KSERVAKERRRQ 80

                  ....*.
gi 1607550604 168 LETYLR 173
Cdd:cd06874    81 LETYLR 86

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  88 ISIPSTILST----GESKPYTLYNI----------------ALRLPLRSFVVQKRYSDFTALHNALTS--------HVGS 139
Cdd:cd06893     2 IRIPKTITAKeykgTGTHPYTLYTVqyetildvqseqnpnaASEQPLATHTVNRRFREFLTLQTRLEEnpkfrkimNVKG 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1607550604 140 PPP--APLPAKSWFKSTVsnpdltESRRRGLETYLRAIAESPD 180
Cdd:cd06893    82 PPKrlFDLPFGNMDKDKI------EARRGLLETFLRQLCSIPE 118

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  87 EISIPSTI-LSTGESKPYTLYNIALRlplrSFVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWFKSTVSNP------- 158
Cdd:cd06867     1 PIQIVDAGkSSEGGSGSYIVYVIRLG----GSEVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSLKDYAKKPskaknda 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1607550604 159 DLTESRRRGLETYLRAIAESPDrrWRDVPAWRAFLN 194
Cdd:cd06867    77 KIIERRKRMLQRFLNRCLQHPI--LRNDIVFQKFLD 110

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  94 ILSTGESKpYTLYNIALRLP----LRSFVVQKRYSDFTALHNAL-TSHvgsppPAPLPAKSW--------FKStvsnpDL 160
Cdd:cd07279    10 TVKEGEKK-YVVYQLAVVQTgdpdTQPAFIERRYSDFLKLYKALrKQH-----PQLMAKVSFprkvlmgnFSS-----EL 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1607550604 161 TESRRRGLETYLRAIAESPdrRWRDVPAWRAFLNLP 196
Cdd:cd07279    79 IAERSRAFEQFLGHILSIP--NLRDSKAFLDFLQGP 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX3 associates with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P). It associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes. It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  87 EISIPSTIlSTGESKpYTLYNIALR--LP---LRSFVVQKRYSDFTALHNALT--SHVGSPPpapLPAKSWFKST----- 154
Cdd:cd07293     5 DVTNPQTV-GVGRGR-FTTYEIRLKtnLPifkLKESTVRRRYSDFEWLRSELEreSKVVVPP---LPGKALFRQLpfrgd 79

                          90       100
                  ....*....|....*....|....*..
gi 1607550604 155 --VSNPDLTESRRRGLETYLRAIAESP 179
Cdd:cd07293    80 dgIFDDSFIEERKQGLEQFLNKVAGHP 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604 103 YTLYNIALR--LPL---RSFVVQKRYSDFTALHNALT---SHVG--SPPPaplPAKSWF--------KSTVSNPDLTESR 164
Cdd:cd07281    18 YVVYKVTTQtsLLMfrsKHFTVKRRFSDFLGLYEKLSekhSQNGfiVPPP---PEKSLIgmtkvkvgKEDSSSAEFLERR 94

                          90
                  ....*....|....*
gi 1607550604 165 RRGLETYLRAIAESP 179
Cdd:cd07281    95 RAALERYLQRIVSHP 109

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1607550604 112 LPLRSFVVQKRYSDFTALHNALTShvgSPPPAPLPAKSWFKSTvsNPDLTESRRRGLETYLRAIAESP 179
Cdd:cd06871    33 SPENSWQVIRRYNDFDLLNASLQI---SGISLPLPPKKLIGNM--DREFIAERQQGLQNYLNVILMNP 95

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  91 PSTILSTGESkpYTLYNIALR-----LPLRSFVVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWFKSTVS--NPDLTES 163
Cdd:cd07283     8 PKKHVCTMET--YITYRVTTKttrteFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDrfSEEFVET 85

                          90
                  ....*....|....*.
gi 1607550604 164 RRRGLETYLRAIAESP 179
Cdd:cd07283    86 RRKALDKFLKRIADHP 101

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604  98 GESKPYTLYNIALR-LPLRSFVVQKRYSDFTALHNALtsHVGSPPPAPLPAKSWFKSTVSNPdLTESRRRGLETYLRAIA 176
Cdd:cd06872    13 SGSKSFAVYSVAVTdNENETWVVKRRFRNFETLHRRL--KEVPKYNLELPPKRFLSSSLDGA-FIEERCKLLDKYLKDLL 89

                  ...
gi 1607550604 177 ESP 179
Cdd:cd06872    90 VIE 92

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1607550604 100 SKPYTLYNIALRLPLRSfvVQKRYSDFTALHNALTSHVGSPPPAPLPAKSWfkSTVSNPDLTESRRRGLETYLRAIAESP 179
Cdd:cd06862    17 LKSFIAYQITPTHTNVT--VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQV--TGRFEEDFIEKRRERLELWMNRLARHP 92

                          90
                  ....*....|....*..
gi 1607550604 180 drRWRDVPAWRAFLNLP 196
Cdd:cd06862    93 --VLSQSEVFRHFLTCT 107

C-terminal SNARE motif of SNAP47; C-terminal SNARE motif of SNAP47, a member of the Qb/Qc subfamily of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins. The exact funtion of SNAP47 is unknown. Qb/Qc SNAREs consist of 2 coiled-coil helices (called SNARE motifs, one belonging to the Qb subgroup and one belonging to the Qc subgroup), which mediate the interactions with other SNARE proteins, and a transmembrane domain. In general, the SNARE complex mediates membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, depending on whether the residue in the hydrophilic center layer of the four-helical bundle is a glutamine (Q) or arginine (R). Qa-, as well as Qb- and Qc-SNAREs, are localized to target organelle membranes, while R-SNARE is localized to vesicle membranes. They form unique complexes consisting of one member of each subgroup, that mediate fusion between a specific type of vesicles and their target organelle. Their SNARE motifs form twisted and parallel heterotetrameric helix bundles. Other members of the Qb/Qc SNAREs are SNAP23, SNAP25, SNAP29 and SEC9.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1607550604 415 DEQVDVLAAIVRRQKEMGVRINEEIETQTEMLDRLNEDTDR 455
Cdd:cd15854     5 EAETQELKQILRKLKSLALEAETELERQDEALDVLSDSVDR 45