The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and 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. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  20 FSCSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 99
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 959479139 100 LILWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 144
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. 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 959479139  20 FSCSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 99
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 959479139 100 LILWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 144
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 33; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139 155 PNEHQDLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQRLGNAFQSISQAFMLDPPHSSETFNNAIS 234
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                 .
gi 959479139 235 H 235
Cdd:cd07669   81 H 81

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 959479139    30 QTKFKGIKTYISYRVTPSHTGRP--VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGR---FEEDFIEKRKRRLILWM 104
Cdd:smart00312   5 EKIGDGKHYYYVIEIETKTGLEEwtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEKYL 84

                           90
                   ....*....|.
gi 959479139   105 NHMTSHPVLSQ 115
Cdd:smart00312  85 QSLLNHPELIN 95

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. 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 959479139  20 FSCSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 99
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 959479139 100 LILWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 144
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; 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. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  20 FSCSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKF-TVISVPHLPEKQATGRFEEDFIEKRKR 98
Cdd:cd07285    1 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFgLAIPIPSLPDKQVTGRFEEEFIKMRME 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 959479139  99 RLILWMNHMTSHPVLSQYEGFEHFLMCADDKQWKLGKRRAEKDEMV 144
Cdd:cd07285   81 RLQAWMTRMCRHPVISESEVFQQFLNFRDEKEWKTGKRKAEKDETV 126

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 33; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139 155 PNEHQDLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQRLGNAFQSISQAFMLDPPHSSETFNNAIS 234
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                 .
gi 959479139 235 H 235
Cdd:cd07669   81 H 81

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 18; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 959479139 160 DLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQRLGNAFQSISQAFMLDPPHSSETFNNAIS 234
Cdd:cd07670    6 DLQDVESRIDGFKAFTKKMDESVLQLNHTANEFARKQVTGFKKEYQKVGQSFKGLSQAFELDQQAFSAGLNQAIA 80

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and 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. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  21 SCSIEDPtkQTKFKGIKTYISYRVTPSHTGRP---VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRK 97
Cdd:cd06093    1 SVSIPDY--EKVKDGGKKYVVYIIEVTTQGGEewtVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERR 78

                         90       100
                 ....*....|....*....|....*.
gi 959479139  98 RRLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06093   79 KQLEQYLQSLLNHPELRNSEELKEFL 104

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 959479139  20 FSCSIEDPTKQTKFkgIKTYISYRV---TPSHTGRP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDF 92
Cdd:cd06861    1 FEITVGDPHKVGDL--TSAHTVYTVrtrTTSPNFEVssfsVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 959479139  93 IEKRKRRLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06861   79 VEQRRAALEKMLRKIANHPVLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 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. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  23 SIEDPTKQtkFKGIKTYISYRVTpSHTGRP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQAT----GRFEE 90
Cdd:cd06860    4 TVDNPEKH--VTTLETYITYRVT-TKTTRSefdsseysVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVkgllDRFSP 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 959479139  91 DFIEKRKRRLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06860   81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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 959479139    30 QTKFKGIKTYISYRVTPSHTGRP--VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGR---FEEDFIEKRKRRLILWM 104
Cdd:smart00312   5 EKIGDGKHYYYVIEIETKTGLEEwtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEKYL 84

                           90
                   ....*....|.
gi 959479139   105 NHMTSHPVLSQ 115
Cdd:smart00312  85 QSLLNHPELIN 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 959479139  23 SIEDPTKQTKfkGIKTYISYRVTPSHTGR-------PVYRRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 91
Cdd:cd07283    4 TVDDPKKHVC--TMETYITYRVTTKTTRTefdlpeySVRRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSEE 81

                         90       100       110
                 ....*....|....*....|....*....|..
gi 959479139  92 FIEKRKRRLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd07283   82 FVETRRKALDKFLKRIADHPVLSFNEHFNVFL 113

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 9; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 959479139 160 DLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQRLGNAFQSISQAFMLDPPHSSETFNNAIS 234
Cdd:cd07668    6 DLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAIT 80

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  53 VYRRYKHFDWLYNRLlHKFTVISVPHLPEK---------QATGRFEEDFIEKRKRRLILWMNHMTSHPvLSQYEGFEHFL 123
Cdd:cd06894   40 VRRRYSDFEWLRSEL-ERDSKIVVPPLPGKalkrqlpfrGDDGIFEEEFIEERRKGLETFINKVAGHP-LAQNEKCLHMF 117

                 ....*
gi 959479139 124 MCADD 128
Cdd:cd06894  118 LQEET 122

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 959479139  53 VYRRYKHFDWLYNRLlhKFTVISVPhLPEKQATGRFEEDFIEKRKRRLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06871   40 VIRRYNDFDLLNASL--QISGISLP-LPPKKLIGNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

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 959479139  34 KGIKTYISYRV---TPSHTGRPV--YRRYKHFDWLYNRLLHKF---TVISVPHLPEK----QATGRFEEDFIEKRKRRLI 101
Cdd:cd07280   17 TGGGAYVVWKItieTKDLIGSSIvaYKRYSEFVQLREALLDEFprhKRNEIPQLPPKvpwyDSRVNLNKAWLEKRRRGLQ 96

                         90       100
                 ....*....|....*....|...
gi 959479139 102 LWMNHMTSHPVLSQYEGFEHFLM 124
Cdd:cd07280   97 YFLNCVLLNPVFGGSPVVKEFLL 119

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  28 TKQTKFKGIKTYISYrvTPSHTGRPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRF---------EEDFIEKRKR 98
Cdd:cd06867    7 AGKSSEGGSGSYIVY--VIRLGGSEVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSLKDYakkpskaknDAKIIERRKR 84

                         90       100
                 ....*....|....*....|....*
gi 959479139  99 RLILWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06867   85 MLQRFLNRCLQHPILRNDIVFQKFL 109

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 959479139  35 GIKTYISYRVTPSHTGRP------VYRRYKHFDWLYNRLLHKFtvisvPHL------PEKQATGRFEEDFIEKRKRRLIL 102
Cdd:cd07279   14 GEKKYVVYQLAVVQTGDPdtqpafIERRYSDFLKLYKALRKQH-----PQLmakvsfPRKVLMGNFSSELIAERSRAFEQ 88

                         90       100
                 ....*....|....*....|.
gi 959479139 103 WMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd07279   89 FLGHILSIPNLRDSKAFLDFL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  53 VYRRYKHFDWLYNRLLHKFTVISVP--------HLPEKQATGRFEEDFIEKRKRRLILWMNHMTSHPvLSQYEGFEHFLM 124
Cdd:cd07294   42 VRRRYSDFEWLKNELERDSKIVVPPlpgkalkrQLPFRGDEGIFEESFIEERRQGLEQFINKIAGHP-LAQNERCLHMFL 120

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  53 VYRRYKHFDWLYNRLLHKFTVISVP--------HLPEKQATGRFEEDFIEKRKRRLILWMNHMTSHPvLSQYEGFEHFLM 124
Cdd:cd07293   40 VRRRYSDFEWLRSELERESKVVVPPlpgkalfrQLPFRGDDGIFDDSFIEERKQGLEQFLNKVAGHP-LAQNERCLHMFL 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 959479139  22 CSIEDPTKQTKFKGIKTYISYRVTPSHtgrpVYRRYKHFDWLYNRLLHKFTVISVpHLPEKQATGR-FEEDFIEKRKRRL 100
Cdd:cd06870    9 SSDEDREKKKRFTVYKVVVSVGRSSWF----VFRRYAEFDKLYESLKKQFPASNL-KIPGKRLFGNnFDPDFIKQRRAGL 83

                         90       100
                 ....*....|....*....|....
gi 959479139 101 ILWMNHMTSHPVLSQYEGFEHFLM 124
Cdd:cd06870   84 DEFIQRLVSDPKLLNHPDVRAFLQ 107

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 959479139  53 VYRRYKHFDWLYNRLLHKFT--VISVPhlPEKQATGRFEEDFIEKRKRRLILWMNHMTSHPVLSQYEGFEHFLmCAD 127
Cdd:cd07276   37 VFRRYTDFVRLNDKLKQMFPgfRLSLP--PKRWFKDNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFF-CLD 110