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 1229766208  563 LRSRVMGAYFEKIGSKSFAVYSIAVTDANNKTWFVKRRYRNFERLHRHLKDIPNYTLHLPPKRIFSSSTEDAFVHQRCIQ 642
Cdd:cd06872      1 LSCRVLGAEIVKSGSKSFAVYSVAVTDNENETWVVKRRFRNFETLHRRLKEVPKYNLELPPKRFLSSSLDGAFIEERCKL 80

                           90       100
                   ....*....|....*....|....*
gi 1229766208  643 LDKYLQELLSIANVAEQHEVWDFLS 667
Cdd:cd06872     81 LDKYLKDLLVIEKVAESHEVWSFLS 105

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  858 WIRRQVLWISKQILQLIMEDAIDDWIVRQIHWLRREDIIAQGIRWVQDVLWPNGTffiqlrnaqseddDTQSTTSRTDES 937
Cdd:pfam08628    1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGL-------------LAEPPPERTEEE 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1229766208  938 KipkpgsfelqleaARRASDVKKMLFGGAPTPLVSLIGNNQYKRCAKDIYYFTQQ 992
Cdd:pfam08628   68 K-------------LRTRKEARKLLLSLIPDALGSVVGRENAREAARRVFDMLQN 109

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 1229766208  563 LRSRVMGAYFEKIGSKSFAVYSIAVTDANNKTWFVKRRYRNFERLHRHLKDIPNYTLHLPPKRIFSSSTEDAFVHQRCIQ 642
Cdd:cd06872      1 LSCRVLGAEIVKSGSKSFAVYSVAVTDNENETWVVKRRFRNFETLHRRLKEVPKYNLELPPKRFLSSSLDGAFIEERCKL 80

                           90       100
                   ....*....|....*....|....*
gi 1229766208  643 LDKYLQELLSIANVAEQHEVWDFLS 667
Cdd:cd06872     81 LDKYLKDLLVIEKVAESHEVWSFLS 105

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  858 WIRRQVLWISKQILQLIMEDAIDDWIVRQIHWLRREDIIAQGIRWVQDVLWPNGTffiqlrnaqseddDTQSTTSRTDES 937
Cdd:pfam08628    1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGL-------------LAEPPPERTEEE 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1229766208  938 KipkpgsfelqleaARRASDVKKMLFGGAPTPLVSLIGNNQYKRCAKDIYYFTQQ 992
Cdd:pfam08628   68 K-------------LRTRKEARKLLLSLIPDALGSVVGRENAREAARRVFDMLQN 109

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 1229766208   571 YFEKIGSKSFAVYSIAVTDANN-KTWFVKRRYRNFERLHRHLK-DIPNYTL-HLPPKRIFSSST--EDAFVHQRCIQLDK 645
Cdd:smart00312    3 EPEKIGDGKHYYYVIEIETKTGlEEWTVSRRYSDFLELHSKLKkHFPRSILpPLPGKKLFGRLNnfSEEFIEKRRRGLEK 82

                            90       100
                    ....*....|....*....|...
gi 1229766208   646 YLQELLSIANVAEQ-HEVWDFLS 667
Cdd:smart00312   83 YLQSLLNHPELINHsEVVLEFLE 105

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 1229766208  563 LRSRVMGAYFEKIGSKSFAVYSIAVTDANNKTWFVKRRYRNFERLHRHLKDIPNYTLHLPPKRIFSSSTEDAFVHQRCIQ 642
Cdd:cd06872      1 LSCRVLGAEIVKSGSKSFAVYSVAVTDNENETWVVKRRFRNFETLHRRLKEVPKYNLELPPKRFLSSSLDGAFIEERCKL 80

                           90       100
                   ....*....|....*....|....*
gi 1229766208  643 LDKYLQELLSIANVAEQHEVWDFLS 667
Cdd:cd06872     81 LDKYLKDLLVIEKVAESHEVWSFLS 105

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  858 WIRRQVLWISKQILQLIMEDAIDDWIVRQIHWLRREDIIAQGIRWVQDVLWPNGTffiqlrnaqseddDTQSTTSRTDES 937
Cdd:pfam08628    1 WLRRRALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGL-------------LAEPPPERTEEE 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1229766208  938 KipkpgsfelqleaARRASDVKKMLFGGAPTPLVSLIGNNQYKRCAKDIYYFTQQ 992
Cdd:pfam08628   68 K-------------LRTRKEARKLLLSLIPDALGSVVGRENAREAARRVFDMLQN 109

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  591 NNKTWFVKRRYRNFERLHRHL-KDIPNYTL-HLPPKRIFSSSTEDaFVHQRCIQLDKYLQELLSIANVAEQHEVWDFLSV 668
Cdd:pfam00787    5 SLEEWSVRRRYSDFVELHKKLlRKFPSVIIpPLPPKRWLGRYNEE-FIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLES 83

                   .
gi 1229766208  669 S 669
Cdd:pfam00787   84 D 84

Domain associated with PX domains; unpubl. observations

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208   106 PIVEAAMKDFIDKLLKDFVVDlWYSEITPDKEFPDQIHALIMDALGEIAVRVKDINLVDLLTRDVVDLVGDHLDLFRRnq 185
Cdd:smart00313    2 AQLEEPLQLLISKIIRDYVQG-WYKGVSEDPSFLREIEQTLEYILRQLYRRLSRQDSAHLILYEILKNLISTITNALE-- 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208   186 aaigvDVMGtlsseERDERLKHHLM----ASKELHPALVSPESEyKVLQRLMSGVLTSVLRPR-ETQCPVVRSIARELLT 260
Cdd:smart00313   79 -----AVLR-----FASPQIPSTEIdlqyAETAIHKALSSPSNE-LTYRRQLVEMLLKFLLPEdSLCSRLHRCLLREVLA 147

                           170       180
                    ....*....|....*....|.
gi 1229766208   261 CLVVQPLMN-FASPGYINELI 280
Cdd:smart00313  148 MQVILPLIThLSDPDTINLCI 168

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  560 VPKLRSRVMGAYFEKIGSKSFAVYSIAVTDAN----NKTWFVKRRYRNFERLHRHLKD-IPN-YTLHLPPKRIFsSSTED 633
Cdd:cd06873      2 KFKLTAVIINTGIVKEHGKTYAVYAISVTRIYpngqEESWHVYRRYSDFHDLHMRLKEkFPNlSKLSFPGKKTF-NNLDR 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1229766208  634 AFVHQRCIQLDKYLQELLSI----ANVAEQHEVWDFLS 667
Cdd:cd06873     81 AFLEKRRKMLNQYLQSLLNPevldANPGLQEIVLDFLE 118

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 1229766208  578 KSFAVYSIAVTDANNKtWFVKRRYRNFERLHRHLKD-IPNYTLHLPPKRIFSSSTEDAFVHQRCIQLDKYLQELLSIANV 656
Cdd:cd06870     18 KRFTVYKVVVSVGRSS-WFVFRRYAEFDKLYESLKKqFPASNLKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVSDPKL 96

                           90
                   ....*....|..
gi 1229766208  657 AEQHEVWDFLSV 668
Cdd:cd06870     97 LNHPDVRAFLQM 108

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 1229766208  578 KSFAVYSIAVTDANNKtWFVKRRYRNFERLHRHLKDI---PNytlhLPPKRIFSSSTEdaFVHQRCIQLDKYLQELLSIA 654
Cdd:cd06880     17 KPYTVFTIEVLVNGRR-HTVEKRYSEFHALHKKLKKSiktPD----FPPKRVRNWNPK--VLEQRRQGLEAYLQGLLKIN 89

                           90
                   ....*....|....
gi 1229766208  655 NVAEQheVWDFLSV 668
Cdd:cd06880     90 ELPKQ--LLDFLGV 101

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 1229766208  576 GSKSFAVYSIAVTDANNkTWFVKRRYRNFERLHRHLKDipNY----TLHLPPKRIFSSSTEDaFVHQRCIQLDKYLQELL 651
Cdd:cd06874     14 GKDEHFEFEVKITVLDE-TWTVFRRYSRFRELHKTMKL--KYpevaALEFPPKKLFGNKSER-VAKERRRQLETYLRNFF 89

                   ..
gi 1229766208  652 SI 653
Cdd:cd06874     90 SV 91

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  563 LRSRVMGAYFEKIGSKSFAVYSIAV---TDANNKTWFVKRRYRNFERLHRHL-KDIPNYT--LHLPPKRI---FSSSTed 633
Cdd:cd07279      1 LKFEIVSARTVKEGEKKYVVYQLAVvqtGDPDTQPAFIERRYSDFLKLYKALrKQHPQLMakVSFPRKVLmgnFSSEL-- 78

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1229766208  634 afVHQRCIQLDKYLQELLSIANVAEQHEVWDFL 666
Cdd:cd07279     79 --IAERSRAFEQFLGHILSIPNLRDSKAFLDFL 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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  591 NNKTWFVKRRYRNFERLHRHLKdIPNYTLHLPPKRIFSSSTEDaFVHQRCIQLDKYLQELLSIANVAEQHEVWDFLSVSS 670
Cdd:cd06871     34 PENSWQVIRRYNDFDLLNASLQ-ISGISLPLPPKKLIGNMDRE-FIAERQQGLQNYLNVILMNPILASCLPVKKFLDPNN 111

                   ....*.
gi 1229766208  671 KNYSFG 676
Cdd:cd06871    112 YSANFT 117

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 1229766208  572 FEKIGS-KSFAVYSIAVTDAN-NKTWFVKRRYRNFERLHRHLKDI-PNYTLH-LPPKRIFSSSTEDAFVHQRCIQLDKYL 647
Cdd:cd06883      7 FQKRYSpEKYYIYVVKVTRENqTEPSFVFRTFEEFQELHNKLSLLfPSLKLPsFPARVVLGRSHIKQVAERRKIELNSYL 86

                           90       100
                   ....*....|....*....|
gi 1229766208  648 QELLSIA-NVAEQHEVWDFL 666
Cdd:cd06883     87 KSLFNASpEVAESDLVYTFF 106

The phosphoinositide binding Phox Homology domain of SNX-like 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1229766208  576 GSKSFAVYSIaVTDANN-----KTWFVKRRYRNF----ERLHRhlkDIPNYTLHLPPKRIFSSSTE---DAFVHQRCIQL 643
Cdd:cd06865     19 GGPPYISYKV-TTRTNIpsythGEFTVRRRFRDVvalaDRLAE---AYRGAFVPPRPDKSVVESQVmqsAEFIEQRRVAL 94

                           90       100
                   ....*....|....*....|....*
gi 1229766208  644 DKYLQELLSIANVAEQHEVWDFLSV 668
Cdd:cd06865     95 EKYLNRLAAHPVIGLSDELRVFLTL 119

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 1229766208  571 YFEKIGSKsFAVYSIAVTDANnktwFVKRRYRNFERLHRHLKDI-PNYTL-HLPPKRIFSSSTEDAFVHQRciQLDKYLQ 648
Cdd:cd06886     13 HVEQNGEK-FVVYNIYMAGRQ----LCSRRYREFANLHQNLKKEfPDFQFpKLPGKWPFSLSEQQLDARRR--GLEQYLE 85

                           90
                   ....*....|....*....
gi 1229766208  649 ELLSIANVAEQHEVWDFLS 667
Cdd:cd06886     86 KVCSIRVIGESDIMQDFLS 104

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 1229766208  576 GSKSFAVYSIAVT--DANNKTWFVKRRYRNFERLHRHLKDI-----PNYTLHLPPKRIFSSST---EDAFVHQRCIQLDK 645
Cdd:cd07280     18 GGGAYVVWKITIEtkDLIGSSIVAYKRYSEFVQLREALLDEfprhkRNEIPQLPPKVPWYDSRvnlNKAWLEKRRRGLQY 97

                           90       100
                   ....*....|....*....|.
gi 1229766208  646 YLQELLSIANVAEQHEVWDFL 666
Cdd:cd07280     98 FLNCVLLNPVFGGSPVVKEFL 118

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform 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. 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. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

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gi 1229766208  578 KSFAVYSIAVTDANNKTWFVKRRYRNFERLHRHL-KDIPNYTL-------HLPpkriFSSSTedafvHQRCIQLDKYLQE 649
Cdd:cd06896     10 KSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLqKQFPSLALpefphwwHLP----FTDSD-----HKRVRDLNHYLEQ 80

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gi 1229766208  650 LLSIA 654
Cdd:cd06896     81 LLSGS 85