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 1896475365  26 FTCSIEDPTKQTKFKGIKTYISYRVTPTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRKRR 105
Cdd:cd07286     1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1896475365 106 LVLWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 150
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 1896475365  26 FTCSIEDPTKQTKFKGIKTYISYRVTPTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRKRR 105
Cdd:cd07286     1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1896475365 106 LVLWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 150
Cdd:cd07286    81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

WASP-binding domain of Sorting nexin protein; The C-terminal region of the Sorting nexin group of proteins appears to carry a BAR-like (Bin/amphiphysin/Rvs) domain. This domain is very diverse and the similarities with other BAR domains are few. In the Sorting nexins it is associated with family PX, pfam00787.13, and in combination with PX appears to be necessary to bind WASP along with p85 to form a multimeric signalling complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365 133 DDKQWKLGKRRAEKDEMVGAHFMLTFQIPNEHQDLQDVEERVDTFKAFAKKMDDSVLQLTHVASELVRKHLGGFRREFQR 212
Cdd:pfam10456   1 DEKEWKTGKRKAEKDELVGAMFFLTIEIPEPPLDLQEVEQKVEGFKRFTKKMDDSVKQLLTVGNEFWKKCTGPFKKEYQK 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1896475365 213 LGNAFQSISHSFTLDPPHSSEPLNNAISHTGRTY 246
Cdd:pfam10456  81 IGSAFQLLSQVFEMDGYVGSSALNEAIAHTGKTY 114

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 1896475365   36 QTKFKGIKTYISYRVTPTHSGRP--VYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGR---FEEDFIDKRKRRLVLWM 110
Cdd:smart00312   5 EKIGDGKHYYYVIEIETKTGLEEwtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEKYL 84

                           90       100
                   ....*....|....*....|
gi 1896475365  111 NHMTSHPVLSQ-YEGFEHFL 129
Cdd:smart00312  85 QSLLNHPELINhSEVVLEFL 104

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 1896475365  26 FTCSIEDPTKQTKFKGIKTYISYRVTPTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRKRR 105
Cdd:cd07286     1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1896475365 106 LVLWMNHMTSHPVLSQYEGFEHFLMC--ADDKQWKLGKRRAEKDEMV 150
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 1896475365 161 PNEHQDLQDVEERVDTFKAFAKKMDDSVLQLTHVASELVRKHLGGFRREFQRLGNAFQSISHSFTLDPPHSSEPLNNAIS 240
Cdd:cd07669     1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                  ....*.
gi 1896475365 241 HTGRTY 246
Cdd:cd07669    81 HTGRTY 86

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 1896475365  26 FTCSIEDPTKQTKFKGIKTYISYRVTPTHSGRPVYRRYKHFDWLYNRLLNKF-TVISVPHLPEKQATGRFEEDFIDKRKR 104
Cdd:cd07285     1 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFgLAIPIPSLPDKQVTGRFEEEFIKMRME 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1896475365 105 RLVLWMNHMTSHPVLSQYEGFEHFLMCADDKQWKLGKRRAEKDEMV 150
Cdd:cd07285    81 RLQAWMTRMCRHPVISESEVFQQFLNFRDEKEWKTGKRKAEKDETV 126

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365 166 DLQDVEERVDTFKAFAKKMDDSVLQLTHVASELVRKHLGGFRREFQRLGNAFQSISHSFTLDPPHSSEPLNNAISHTGRT 245
Cdd:cd07670     6 DLQDVESRIDGFKAFTKKMDESVLQLNHTANEFARKQVTGFKKEYQKVGQSFKGLSQAFELDQQAFSAGLNQAIAFTGEA 85

                  .
gi 1896475365 246 Y 246
Cdd:cd07670    86 Y 86

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 1896475365  27 TCSIEDPtkQTKFKGIKTYISYRVTPTHSGRP---VYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRK 103
Cdd:cd06093     1 SVSIPDY--EKVKDGGKKYVVYIIEVTTQGGEewtVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERR 78

                          90       100
                  ....*....|....*....|....*.
gi 1896475365 104 RRLVLWMNHMTSHPVLSQYEGFEHFL 129
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 1896475365  26 FTCSIEDPTKQTKFkgIKTYISYRV---TPTHSGRP----VYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDF 98
Cdd:cd06861     1 FEITVGDPHKVGDL--TSAHTVYTVrtrTTSPNFEVssfsVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1896475365  99 IDKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 129
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 1896475365  29 SIEDPTKQtkFKGIKTYISYRVTpTHSGRP--------VYRRYKHFDWLYNRLLNKFTVISVPHLPEKQAT----GRFEE 96
Cdd:cd06860     4 TVDNPEKH--VTTLETYITYRVT-TKTTRSefdsseysVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVkgllDRFSP 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1896475365  97 DFIDKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 129
Cdd:cd06860    81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365  45 YISYRVTPTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRKRRLVLWMNHMTSHPVLSQYEG 124
Cdd:cd06866    18 HVEYEVSSKRFKSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVLSEDEL 97

                  ....*
gi 1896475365 125 FEHFL 129
Cdd:cd06866    98 VRTFL 102

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365 166 DLQDVEERVDTFKAFAKKMDDSVLQLTHVASELVRKHLGGFRREFQRLGNAFQSISHSFTLDPPHSSEPLNNAISHTGRT 245
Cdd:cd07668     6 DLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAITEAGKT 85

                  .
gi 1896475365 246 Y 246
Cdd:cd07668    86 Y 86

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 1896475365  29 SIEDPTKQTKfkGIKTYISYRVTpTHSGR--------PVYRRYKHFDWLYNRLLNKFTVISVPHLPEK----QATGRFEE 96
Cdd:cd07283     4 TVDDPKKHVC--TMETYITYRVT-TKTTRtefdlpeySVRRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSE 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1896475365  97 DFIDKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 129
Cdd:cd07283    81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFL 113

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 1896475365  21 DNPNPFTCSIEdpTKQTKfKGIKTYIsYRV----TPTHSGRpVYRRYKHFDWLYNRLlnKFTVISVPhLPEKQATGRFEE 96
Cdd:cd06871     3 DDTVPLTCVIE--ASQNI-QSHTEYI-IRVqrgpSPENSWQ-VIRRYNDFDLLNASL--QISGISLP-LPPKKLIGNMDR 74

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1896475365  97 DFIDKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 129
Cdd:cd06871    75 EFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

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 1896475365  32 DPTKQ----TKFKGIKTYISYRVT-------PTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEK---QATGRFEED 97
Cdd:cd06865     6 DPKKEqepsRVPLGGPPYISYKVTtrtnipsYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKsvvESQVMQSAE 85

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1896475365  98 FIDKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 129
Cdd:cd06865    86 FIEQRRVALEKYLNRLAAHPVIGLSDELRVFL 117

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 1896475365  34 TKQTKFKGIKTYISYrvTPTHSGRPVYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRF---------EEDFIDKRKR 104
Cdd:cd06867     7 AGKSSEGGSGSYIVY--VIRLGGSEVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSLKDYakkpskaknDAKIIERRKR 84

                          90       100
                  ....*....|....*....|....*
gi 1896475365 105 RLVLWMNHMTSHPVLSQYEGFEHFL 129
Cdd:cd06867    85 MLQRFLNRCLQHPILRNDIVFQKFL 109

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1896475365  59 VYRRYKHFDWLYNRLLNKFTVISVPHLPEKQATGRFEEDFIDKRKRRLVLWMNHMTSHPVL 119
Cdd:cd07295    40 VRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVIEERRQGLETFLQSVAGHPLL 100

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 1896475365  41 GIKTYISYRVTPTHSGRP------VYRRYKHFDWLYNRLLNKFtvisvPHL------PEKQATGRFEEDFIDKRKRRLVL 108
Cdd:cd07279    14 GEKKYVVYQLAVVQTGDPdtqpafIERRYSDFLKLYKALRKQH-----PQLmakvsfPRKVLMGNFSSELIAERSRAFEQ 88

                          90       100
                  ....*....|....*....|.
gi 1896475365 109 WMNHMTSHPVLSQYEGFEHFL 129
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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365  59 VYRRYKHFDWLYNRLLNKFTVISVP--------HLPEKQATGRFEEDFIDKRKRRLVLWMNHMTSHPvLSQYEGFEHFLM 130
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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365  59 VYRRYKHFDWLYNRLLNKFTVISVP--------HLPEKQATGRFEEDFIDKRKRRLVLWMNHMTSHPvLSQYEGFEHFLM 130
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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1896475365  43 KTYISYRVTpTHSGRP---VYRRYKHFDWLYNRLLNKFTVISVpHLPEKQATGR-FEEDFIDKRKRRLVLWMNHMTSHPV 118
Cdd:cd06870    18 KRFTVYKVV-VSVGRSswfVFRRYAEFDKLYESLKKQFPASNL-KIPGKRLFGNnFDPDFIKQRRAGLDEFIQRLVSDPK 95

                          90
                  ....*....|..
gi 1896475365 119 LSQYEGFEHFLM 130
Cdd:cd06870    96 LLNHPDVRAFLQ 107

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1896475365  59 VYRRYKHFDWLYNRLLNKFTVI----SVPHLPEKQATGRFEEDFIDKRKRRLVLWMNHMTSHPVLSQYEGFEHFLM 130
Cdd:cd06881    40 VWKRYSDFKKLHRELSRLHKQLylsgSFPPFPKGKYFGRFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115