The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   1 MEVYIPSFRYEESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLET 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 578810304  81 YLQAVILENeELPKLFLDFLNVRHLPSLPKA 111
Cdd:cd06880   81 YLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   1 MEVYIPSFRYEESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLET 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 578810304  81 YLQAVILENeELPKLFLDFLNVRHLPSLPKA 111
Cdd:cd06880   81 YLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 110

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 578810304     9 RYEESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV----RNWVPKVLEQRRQGLETY 81
Cdd:smart00312   4 PEKIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRsilPPLPGKKLfgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|...
gi 578810304    82 LQAvILENEELP---KLFLDFLN 101
Cdd:smart00312  84 LQS-LLNHPELInhsEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   1 MEVYIPSFRYEESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLET 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEA 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 578810304  81 YLQAVILENeELPKLFLDFLNVRHLPSLPKA 111
Cdd:cd06880   81 YLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 110

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; 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 fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   1 MEVYIPSfrYEESdlERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKTP---EIPSKHvRNWV----PKVLEQ 73
Cdd:cd06897    1 LEISIPT--TSVS--PKPYTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEppyPLPPKS-WFLStssnPKLVEE 75

                         90       100       110
                 ....*....|....*....|....*....|....
gi 578810304  74 RRQGLETYLQAvILENEELP----KLFLDFLNVR 103
Cdd:cd06897   76 RRVGLEAFLRA-LLNDEDSRwrnsPAVKEFLNLP 108

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 578810304     9 RYEESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV----RNWVPKVLEQRRQGLETY 81
Cdd:smart00312   4 PEKIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRsilPPLPGKKLfgrlNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|...
gi 578810304    82 LQAvILENEELP---KLFLDFLN 101
Cdd:smart00312  84 LQS-LLNHPELInhsEVVLEFLE 105

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 578810304  11 EESDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKciKTP----EIPSKHV--RNWVPKVLEQRRQGLETYLQA 84
Cdd:cd06870   12 EDREKKKRFTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKK--QFPasnlKIPGKRLfgNNFDPDFIKQRRAGLDEFIQR 89

                         90       100
                 ....*....|....*....|
gi 578810304  85 VILENE--ELPKlFLDFLNV 102
Cdd:cd06870   90 LVSDPKllNHPD-VRAFLQM 108

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 578810304   1 MEVYIPSFRYEESDLERgYTVFKIEvlMNGRkHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHVRNWVPKVLEQRRQG 77
Cdd:cd06886    4 VPISIPDYKHVEQNGEK-FVVYNIY--MAGR-QLCSRRYREFANLHQNLKKEFPDfqfPKLPGKWPFSLSEQQLDARRRG 79

                 ....*...
gi 578810304  78 LETYLQAV 85
Cdd:cd06886   80 LEQYLEKV 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  29 NGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV------RNWVPKVLEQRRQGLETYLQAVILENeELPKLFL-- 97
Cdd:COG5391  169 ESRPLVVRRRYSDFESLHSILIKLLPLcaiPPLPSKKSnseyygDRFSDEFIEERRQSLQNFLRRVSTHP-LLSNYKNsk 247

                         90       100       110
                 ....*....|....*....|....*....|
gi 578810304  98 DFLNVRHLPSLPKAEScGSFDETESEESSK 127
Cdd:COG5391  248 SWESHSTLLSSFIENR-KSVPTPLSLDLTS 276

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   2 EVYIPSFRYEESDLERGYTVFKIEVLMNGRKHF-----VEKRYSEFHALHKKLKKciKTPEI-----PSKHV---RNWVP 68
Cdd:cd06876   21 RVSIQSYISDVEEEGKEFVVYLIEVQRLNNDDQssgwvVARRYSEFLELHKYLKK--RYPGVlkldfPQKRKislKYSKT 98

                         90
                 ....*....|....*....
gi 578810304  69 KVLEQRRQGLETYLQAVIL 87
Cdd:cd06876   99 LLVEERRKALEKYLQELLK 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   5 IPSFRYEESDLERGYTVFKIEVLM-NGRKHFVEKRYSEFHALHKKLKKC-----IKTPeiPSKHVR-NWVPKVLEQRRQG 77
Cdd:cd07276    6 PPILGYEVMEERARFTVYKIRVENkVGDSWFVFRRYTDFVRLNDKLKQMfpgfrLSLP--PKRWFKdNFDPDFLEERQLG 83

                 ....*....
gi 578810304  78 LETYLQAVI 86
Cdd:cd07276   84 LQAFVNNIM 92

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 578810304  35 VEKRYSEFHALHKKLKKC-IKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAV----ILENEELPKLFLD 98
Cdd:cd06871   40 VIRRYNDFDLLNASLQISgISLPLPPKKLIGNMDREFIAERQQGLQNYLNVIlmnpILASCLPVKKFLD 108

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  11 EESDLERGYTVFKIEV-LMNGRKHFVEKRYSEFHALHKKL------------KKCIkTPEIPSKHVRNWVPKVLEQRRQG 77
Cdd:cd06882   12 EEKRGFTNYYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLeerfgpeagssaYDCT-LPTLPGKIYVGRKAEIAERRIPL 90

                 ....*.
gi 578810304  78 LETYLQ 83
Cdd:cd06882   91 LNRYMK 96

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; 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. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  14 DLERGYTVFKIEVLMN----GRKH-FVEKRYSEFHALHKKLKK---CIKTPEIPSKHV--RNWVPKVLEQRRQGLETYLQ 83
Cdd:cd06898   13 DDWGSYTDYEIFLHTNsmcfTLKTsCVRRRYSEFVWLRNRLQKnalLIQLPSLPPKNLfgRFNNEGFIEERQQGLQDFLE 92

                 ...
gi 578810304  84 AVI 86
Cdd:cd06898   93 KVL 95

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304   8 FRYEESDLERGYTVFKIEVLMNGRKH--FVEKRYSEFHALHKKLKK---CIKTPEIPSKHV--RNWVPKVLEQRRQGLET 80
Cdd:cd06883    5 FGFQKRYSPEKYYIYVVKVTRENQTEpsFVFRTFEEFQELHNKLSLlfpSLKLPSFPARVVlgRSHIKQVAERRKIELNS 84

                         90
                 ....*....|.
gi 578810304  81 YLQAVILENEE 91
Cdd:cd06883   85 YLKSLFNASPE 95

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578810304  35 VEKRYSEFHALHKKLKKciKTPEIPS------KHVRNWVPKVLEQRRQGLETYLQaVILENEEL---PKLF---LDFL 100
Cdd:cd06873   43 VYRRYSDFHDLHMRLKE--KFPNLSKlsfpgkKTFNNLDRAFLEKRRKMLNQYLQ-SLLNPEVLdanPGLQeivLDFL 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; 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 is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578810304  35 VEKRYSEFHALHKKLKKCIK--TPEIPSKHVRNWVP----------KVLEQRRQGLETYLQAV----ILENEELPKLFL 97
Cdd:cd06894   40 VRRRYSDFEWLRSELERDSKivVPPLPGKALKRQLPfrgddgifeeEFIEERRKGLETFINKVaghpLAQNEKCLHMFL 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  16 ERGYTVFKIEVLMNGRKH-------FVEKRYSEFHALHKKL--------KKCIKTPEIPSKHV-RNWVPKVLEQRRQGLE 79
Cdd:cd07288   14 PKGYTEYKVTAQFISKKQpedvkevVVWKRYSDLKKLHGELaythrnlfRRQEEFPPFPRAQVfGRFEAAVIEERRNAAE 93

                 ....
gi 578810304  80 TYLQ 83
Cdd:cd07288   94 AMLL 97

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; 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. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578810304  35 VEKRYSEFHALHKKLKKCI---KTPEIPSKHV-RNWVPKVLEQRRQGLETYLQAV----ILENEELPKLFL 97
Cdd:cd06866   32 VYRRYSDFVWLHEYLLKRYpyrMVPALPPKRIgGSADREFLEARRRGLSRFLNLVarhpVLSEDELVRTFL 102

The phosphoinositide binding Phox Homology domain of RPK118-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 bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  16 ERGYTVFKIEVLMNGRKH-------FVEKRYSEFHALHKKLKKCIKT---------PEIPSKHVRNWVPKVLEQRRQGLE 79
Cdd:cd07287   14 PKGYTVYKVTARIVSRKNpedvqeiVVWKRYSDFKKLHKDLWQIHKNlcrqselfpPFAKAKVFGRFDESVIEERRQCAE 93

                 ....
gi 578810304  80 TYLQ 83
Cdd:cd07287   94 DLLQ 97

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; 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. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810304  19 YTVFKIE---VLMNGRKHFVEK------RYSEFHALHKKLKKC---IKTPEIPSKHVR---------NWVPKVLEQRRQG 77
Cdd:cd06864   23 YTVYLIEtkiVEHESEEGLSKKlsslwrRYSEFELLRNYLVVTypyVIVPPLPEKRAMfmwqklssdTFDPDFVERRRAG 102

                         90       100
                 ....*....|....*....|....*.
gi 578810304  78 LETYLQAVIlENEEL--PKLFLDFLN 101
Cdd:cd06864  103 LENFLLRVA-GHPELcqDKIFLEFLT 127