The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  127 DDKQWKLGKRRAEKDEMVGAHFMLTLQIPNEHQDLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQR 206
Cdd:pfam10456   1 DEKEWKTGKRKAEKDELVGAMFFLTIEIPEPPLDLQEVEQKVEGFKRFTKKMDDSVKQLLTVGNEFWKKCTGPFKKEYQK 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 444295061  207 LGNSFQSISQAFMLEPPHSSDSLNNAISHTGR 238
Cdd:pfam10456  81 IGSAFQLLSQVFEMDGYVGSSALNEAIAHTGK 112

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 444295061  127 DDKQWKLGKRRAEKDEMVGAHFMLTLQIPNEHQDLQDVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQR 206
Cdd:pfam10456   1 DEKEWKTGKRKAEKDELVGAMFFLTIEIPEPPLDLQEVEQKVEGFKRFTKKMDDSVKQLLTVGNEFWKKCTGPFKKEYQK 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 444295061  207 LGNSFQSISQAFMLEPPHSSDSLNNAISHTGR 238
Cdd:pfam10456  81 IGSAFQLLSQVFEMDGYVGSSALNEAIAHTGK 112

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 444295061   53 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 444295061  53 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQY 116
Cdd:COG5391  175 VRRRYSDFESLHSILIKLLPLCAIPPLPSKKsnseyYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNY 243

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  20 FSVSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 99
Cdd:cd06862    1 YHCTVTNPKKESKFKGLKSFIAYQITPTHTNVTVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDFIEKRRER 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 444295061 100 LVLWMNHMTSHPVLSQYEGFEHFLMCADDKQWKLGKRRAEKDEMV 144
Cdd:cd06862   81 LELWMNRLARHPVLSQSEVFRHFLTCTDEKDWKSGKRKAEKDELV 125

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 444295061  20 FSVSIEDPTKQTKFKGIKTYISYRVTPSHTGRPVYRRYKHFDWLYNRLLHKF-TVISVPHLPEKQATGRFEEDFIEKRKR 98
Cdd:cd07285    1 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFgLAIPIPSLPDKQVTGRFEEEFIKMRME 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 444295061  99 RLVLWMNHMTSHPVLSQYEGFEHFLMCADDKQWKLGKRRAEKDEMV 144
Cdd:cd07285   81 RLQAWMTRMCRHPVISESEVFQQFLNFRDEKEWKTGKRKAEKDETV 126

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  20 FSVSIEDPTKQTKfkGIKTYISYRV---TPSHTGRP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEE-- 90
Cdd:cd06859    1 FEISVTDPVKVGD--GMSAYVVYRVttkTNLPDFKKsefsVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVkf 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 444295061  91 DFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06859   79 EFIEKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 9 and Similar Proteins; 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. This subfamily consists of SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. 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 444295061 163 DVEERVDSFKAFAKKMDDSVMQLTHVASELVRKHLGGFRKEFQRLGNSFQSISQAFMLEPPHSSDSLNNAISHTGR 238
Cdd:cd07626    1 DVEQQVDAFKKFVKSMDDSVKNLINIAQEQAKKHQGPYKKEYQKIGQAFTSLGTAFELDETPTSVPLTQAIKHTGQ 76

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 444295061  20 FSVSIEDPTKQTKFkgIKTYISYRV---TPSHTGRP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDF 92
Cdd:cd06861    1 FEITVGDPHKVGDL--TSAHTVYTVrtrTTSPNFEVssfsVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 444295061  93 IEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 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 444295061  22 VSIEDPTKQtkFKGIKTYISYRVTpSHTGRP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQAT----GRFE 89
Cdd:cd06860    3 ITVDNPEKH--VTTLETYITYRVT-TKTTRSefdsseysVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVkgllDRFS 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 444295061  90 EDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06860   80 PEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  20 FSVSIEDPTKQTKfKGIKTYISYRVTpSHTGRP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATG 86
Cdd:cd06863    1 LECLVSDPQKELD-GSSDTYISYLIT-TKTNLPsfsrkefkVRRRYSDFVFLHECLSNDFPACVVPPLPDKHrleyiTGD 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 444295061  87 RFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06863   79 RFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  22 VSIEDPtkQTKFKGIKTYISYRVTpSHTGR--------PVYRRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFE 89
Cdd:cd07284    3 ITVDEP--ESHVTAIETFITYRVM-TKTSRsefdssefEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKfvmkGMVERFN 79

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 444295061  90 EDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFLMCA 126
Cdd:cd07284   80 EDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  20 FSVSIEDPTKQTKFKGIK---TYISYRV--TPSHTGRP---------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQA- 84
Cdd:cd06864    1 MEITVTEAEKRTGGSAMNlkeTYTVYLIetKIVEHESEeglskklssLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAm 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 444295061  85 -------TGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06864   81 fmwqklsSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 444295061  53 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQY 116
Cdd:COG5391  175 VRRRYSDFESLHSILIKLLPLCAIPPLPSKKsnseyYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNY 243

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  21 SVSIEDPTKQTKFKGiKTYISYRVTpSHTGRP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFE-ED 91
Cdd:cd06898    1 SVEVRDPRTHKEDDW-GSYTDYEIF-LHTNSMcftlktscVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNnEG 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 444295061  92 FIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06898   79 FIEERQQGLQDFLEKVLQTPLLLSDSRLHLFL 110

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 444295061  53 VYRRYKHFDWLYNRLlhKFTVISVPhLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd06871   40 VIRRYNDFDLLNASL--QISGISLP-LPPKKLIGNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

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 444295061  53 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPVL 113
Cdd:cd07295   40 VRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVIEERRQGLETFLQSVAGHPLL 100

The phosphoinositide binding Phox Homology domain of Sorting Nexin 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX2 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444295061  22 VSIEDPTKQTKfkGIKTYISYRVTP-------SHTGRPVYRRYKHFDWLYNRLLHKFTVIS--VPHLPEKQATGRFE--- 89
Cdd:cd07282    3 IGVSDPEKVGD--GMNAYMAYRVTTktslsmfSRSEFSVRRRFSDFLGLHSKLASKYLHVGyiVPPAPEKSIVGMTKvkv 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 444295061  90 --ED-----FIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd07282   81 gkEDsssteFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 121

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

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gi 444295061  21 SVSIEDPTKQTKfkGIKTYISYRVTpSHTGRPVY--------RRYKHFDWLYNRLLHKFTV--ISVPHLPEKQATGRFE- 89
Cdd:cd07281    2 KVSITDPEKIGD--GMNAYVVYKVT-TQTSLLMFrskhftvkRRFSDFLGLYEKLSEKHSQngFIVPPPPEKSLIGMTKv 78

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gi 444295061  90 ----ED-----FIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFL 123
Cdd:cd07281   79 kvgkEDsssaeFLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

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 444295061  53 VYRRYKHFDWLYNRLLHKFTVISVP--------HLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPvLSQYEGFEHFLM 124
Cdd:cd07294   42 VRRRYSDFEWLKNELERDSKIVVPPlpgkalkrQLPFRGDEGIFEESFIEERRQGLEQFINKIAGHP-LAQNERCLHMFL 120

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.

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gi 444295061  53 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFLM 124
Cdd:cd06873   43 VYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVL 114

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.

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gi 444295061  53 VYRRYKHFDWLYNRLLHKFTVI----SVPHLPEKQATGRFEEDFIEKRKRRLVLWMNHMTSHPVLSQYEGFEHFLM 124
Cdd:cd06881   40 VWKRYSDFKKLHRELSRLHKQLylsgSFPPFPKGKYFGRFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115