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 188595660 365 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLSTVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSEALNNAIS 444
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 445 HTGRTYETVGEMFAGQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 188595660 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRMY 571
Cdd:cd07669  161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

Src Homology 3 domain of Sorting Nexin 33; 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). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188595660   4 KGRALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11896    1 KARALYSFQSENKEEINIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 55

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 188595660 365 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLSTVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSEALNNAIS 444
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 445 HTGRTYETVGEMFAGQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 188595660 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRMY 571
Cdd:cd07669  161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

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 188595660 230 FACSIEDPTKQTKFKGIKSYISYKLTPTHAGSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 309
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 188595660 310 LILWMDHMTSHPVLSQYEGFQHFLSC--LDDKQWKMGKRRAEKDEMV 354
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 188595660  263 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 188595660     4 KGRALYDFHSENKEEISIQQDEDLVIFSETSlDGWLQGQNSRGETGLFPASYVE 57
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLEKSD-DGWWKGRLGRGKEGLFPSNYVE 56

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 188595660    7 ALYDFHSENKEEISIQQDeDLVIFSETSLDGWLQGQNsRGETGLFPASYVE 57
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRG-DVITVIEESEDGWWEGIN-TGRTGLVPANYVE 49

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 188595660 365 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLSTVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSEALNNAIS 444
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 445 HTGRTYETVGEMFAGQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 188595660 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRMY 571
Cdd:cd07669  161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 373 DVEDRVDAFKAFSKKMDDSVLQLSTVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSEALNNAISHTGRTYET 452
Cdd:cd07626    1 DVEQQVDAFKKFVKSMDDSVKNLINIAQEQAKKHQGPYKKEYQKIGQAFTSLGTAFELDETPTSVPLTQAIKHTGQAYEE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 453 VGEMFAGQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVGFALQAEMN 532
Cdd:cd07626   81 IGELFAEQPKHDLIPLLDGLHEYKGLLSTFPDIIGVHKGAVQKVKECERLVDEGKMSSAELEEVKRRTDVISYALLAEIN 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 188595660 533 HFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRMY 571
Cdd:cd07626  161 HFHRERVRDFKSMMRNYLQQQIEFYQKIAAKLEEALAMY 199

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 188595660 230 FACSIEDPTKQTKFKGIKSYISYKLTPTHAGSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 309
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 188595660 310 LILWMDHMTSHPVLSQYEGFQHFLSC--LDDKQWKMGKRRAEKDEMV 354
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

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 188595660 370 DLQDVEDRVDAFKAFSKKMDDSVLQLSTVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSEALNNAISHTGRT 449
Cdd:cd07668    6 DLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAITEAGKT 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 450 YETVGEMFAGQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVGFALQA 529
Cdd:cd07668   86 YEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMSYALQA 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 188595660 530 EMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRMY 571
Cdd:cd07668  166 EMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRF 207

Src Homology 3 domain of Sorting Nexin 33; 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). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188595660   4 KGRALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11896    1 KARALYSFQSENKEEINIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 55

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 188595660 233 SIEDPTKQTKfkGIKSYISYKLT-----PTHAGSP--VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEE--DFI 303
Cdd:cd06859    4 SVTDPVKVGD--GMSAYVVYRVTtktnlPDFKKSEfsVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVkfEFI 81

                         90       100       110
                 ....*....|....*....|....*....|
gi 188595660 304 EKRKRRLILWMDHMTSHPVLSQYEGFQHFL 333
Cdd:cd06859   82 EKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188595660   4 KGRALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11897    1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVEV 55

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 188595660 230 FACSIEDPTKQTKFkgIKSYISYKL---TPTHAGSP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDF 302
Cdd:cd06861    1 FEITVGDPHKVGDL--TSAHTVYTVrtrTTSPNFEVssfsVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 188595660 303 IEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd06861   79 VEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660   240 QTKFKGIKSYISYKLTptHAGSP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGR---FEEDFIEKRKRRLIL 312
Cdd:smart00312   5 EKIGDGKHYYYVIEIE--TKTGLeewtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEK 82

                           90       100
                   ....*....|....*....|...
gi 188595660   313 WMDHMTSHPVLSQ-YEGFQHFLS 334
Cdd:smart00312  83 YLQSLLNHPELINhSEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 188595660 260 GSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd06866   29 KSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLT 103

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 188595660 233 SIEDPTKQTKfkGIKSYISY----KLTPTHAGSPVY---RRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 301
Cdd:cd07283    4 TVDDPKKHVC--TMETYITYrvttKTTRTEFDLPEYsvrRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSEE 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 188595660 302 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd07283   82 FVETRRKALDKFLKRIADHPVLSFNEHFNVFLT 114

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 188595660 233 SIEDPtkQTKFKGIKSYISYKL-TPTHAGS------PVYRRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 301
Cdd:cd07284    4 TVDEP--ESHVTAIETFITYRVmTKTSRSEfdssefEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKfvmkGMVERFNED 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 188595660 302 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd07284   82 FIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 114

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 188595660   6 RALYDFHSENKEEISIQQDEDLVIFSETSLD-GWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11767    3 VALYPFTGENDEELSFEKGERLEIIEKPEDDpDWWKARNALGTTGLVPRNYVEV 56

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 188595660   7 ALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11761    6 VLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (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. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 188595660   4 KGRALYDFHSE-NKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEIV 59
Cdd:cd11898    1 KARVLYDFAAEpGNNELTVKEGEIITVTNPNVGGGWIEAKNSQGERGLVPTDYVEIV 57

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 188595660   6 RALYDFHSENKEEISIQQDeDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11819    3 KALYDYQAAEDNEISFVEG-DIITQIEQIDEGWWLGVNAKGQKGLFPANYVEL 54

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; 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. 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 188595660 382 KAFSKKMDDSVLQLSTVAAELVrKHVGGFRKEFQKLGSAFQAISHAFQMdppfRSEALNNAISHTGRTYETVGEMFAGQP 461
Cdd:cd07596   10 KDYILKLEEQLKKLSKQAQRLV-KRRRELGSALGEFGKALIKLAKCEEE----VGGELGEALSKLGKAAEELSSLSEAQA 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595660 462 KHDLFQMLDTLSLYQGLLSNFPDII-------------------------HLQKGAFAKVKESQRMSDEGRMAQEEADGI 516
Cdd:cd07596   85 NQELVKLLEPLKEYLRYCQAVKETLddradalltlqslkkdlaskkaqleKLKAAPGIKPAKVEELEEELEEAESALEEA 164

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 188595660 517 RRRCRVVGFALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLRM 570
Cdd:cd07596  165 RKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAWESLLPE 218

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 188595660   6 RALYDFHSENKEEISIQqDEDLVIFSETSLDGWLQGQNSR-GETGLFPASYVE 57
Cdd:cd11789    3 RAMYDYAAADDDEVSFQ-EGDVIINVEIIDDGWMEGTVQRtGQSGMLPANYVE 54

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 188595660 234 IEDPTKQTKFKGiKSYISYKLTpTHAGSP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFE-EDFIE 304
Cdd:cd06898    4 VRDPRTHKEDDW-GSYTDYEIF-LHTNSMcftlktscVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNnEGFIE 81

                         90       100
                 ....*....|....*....|....*....
gi 188595660 305 KRKRRLILWMDHMTSHPVLSQYEGFQHFL 333
Cdd:cd06898   82 ERQQGLQDFLEKVLQTPLLLSDSRLHLFL 110

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 188595660   6 RALYDFHSEN-KEEISIQQDEDLVIFSETSLDG----WLQGQNSRGETGLFPASYVEI 58
Cdd:cd11771    3 RALYDFTPENpEMELSLKKGDIVAVLSKTDPLGrdseWWKGRTRDGRIGWFPSNYVEV 60

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 188595660   4 KGRALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11911    1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTRVRKNNGDEGYVPTSYIEV 55

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 188595660   6 RALYDFHSENKEEISIQQDEDLVIFSETSLDGWLQGQNSRGETGLFPASYVE 57
Cdd:cd11998    4 RALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVE 55

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 188595660 261 SPVYRRYKHFDWLYNRLlHKFTVISVPHLPEK---------QATGRFEEDFIEKRKRRLILWMDHMTSHPvLSQYE 327
Cdd:cd06894   38 SSVRRRYSDFEWLRSEL-ERDSKIVVPPLPGKalkrqlpfrGDDGIFEEEFIEERRKGLETFINKVAGHP-LAQNE 111

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 188595660    6 RALYDFHSENKEEISIQQDEDLVIFSEtSLDGWLQGQNSRGETGLFPA 53
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEK-SEDGWWKGRNKGGKEGLIPS 47

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 188595660   8 LYDFHSENKEEISIQQDEDLVIFSETSlDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11962    5 LYDYEKDEDNEIELVEGEIVTNIEMVD-EDWWMGTNSKGESGLFPSNYVEL 54

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 188595660 261 SPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVL 323
Cdd:cd07295   38 SSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVIEERRQGLETFLQSVAGHPLL 100

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 188595660 238 TKQTKFKGIKSYISYklTPTHAGSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRF---------EEDFIEKRKR 308
Cdd:cd06867    7 AGKSSEGGSGSYIVY--VIRLGGSEVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSLKDYakkpskaknDAKIIERRKR 84

                         90       100
                 ....*....|....*....|....*..
gi 188595660 309 RLILWMDHMTSHPVLSQYEGFQHFLSC 335
Cdd:cd06867   85 MLQRFLNRCLQHPILRNDIVFQKFLDP 111