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 677540546 355 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLTNVASELVRKHVGGFRKEFQKLGNAFQAISHSFHMDPPYSSDALNNAIS 434
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 435 HTGKTYETVGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQEEADGIRKRCRVVG 514
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 677540546 515 FALQAEMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTLHMY 561
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 677540546   4 KARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 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 677540546 355 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLTNVASELVRKHVGGFRKEFQKLGNAFQAISHSFHMDPPYSSDALNNAIS 434
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 435 HTGKTYETVGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQEEADGIRKRCRVVG 514
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 677540546 515 FALQAEMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTLHMY 561
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 677540546 220 FICSVEDPTKQTKFKGIKSYISYKLTPSNINSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 299
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 677540546 300 LILWMDHMTSHPVLSQYEGFQHFLCC--RDEKQWKLGKRRAEKDEMV 344
Cdd:cd07286   81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677540546  245 TPSNINSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:pfam00787   3 TFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546   230 QTKFKGIKSYISYKLTPSNINSP--VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGR---FEEDFIEKRKRRLILWM 304
Cdd:smart00312   5 EKIGDGKHYYYVIEIETKTGLEEwtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEKYL 84

                           90       100
                   ....*....|....*....|
gi 677540546   305 DHMTSHPVLSQ-YEGFQHFL 323
Cdd:smart00312  85 QSLLNHPELINhSEVVLEFL 104

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677540546 253 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQY 316
Cdd:COG5391  175 VRRRYSDFESLHSILIKLLPLCAIPPLPSKKsnseyYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNY 243

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 677540546 355 PTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLTNVASELVRKHVGGFRKEFQKLGNAFQAISHSFHMDPPYSSDALNNAIS 434
Cdd:cd07669    1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 435 HTGKTYETVGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQEEADGIRKRCRVVG 514
Cdd:cd07669   81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 677540546 515 FALQAEMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTLHMY 561
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 677540546 363 DVEDRVDAFKAFSKKMDDSVLQLTNVASELVRKHVGGFRKEFQKLGNAFQAISHSFHMDPPYSSDALNNAISHTGKTYET 442
Cdd:cd07626    1 DVEQQVDAFKKFVKSMDDSVKNLINIAQEQAKKHQGPYKKEYQKIGQAFTSLGTAFELDETPTSVPLTQAIKHTGQAYEE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 443 VGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQEEADGIRKRCRVVGFALQAEMN 522
Cdd:cd07626   81 IGELFAEQPKHDLIPLLDGLHEYKGLLSTFPDIIGVHKGAVQKVKECERLVDEGKMSSAELEEVKRRTDVISYALLAEIN 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 677540546 523 HFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTLHMY 561
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 677540546 220 FICSVEDPTKQTKFKGIKSYISYKLTPSNINSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 299
Cdd:cd07286    1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 677540546 300 LILWMDHMTSHPVLSQYEGFQHFLCC--RDEKQWKLGKRRAEKDEMV 344
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 677540546 360 DLQDVEDRVDAFKAFSKKMDDSVLQLTNVASELVRKHVGGFRKEFQKLGNAFQAISHSFHMDPPYSSDALNNAISHTGKT 439
Cdd:cd07668    6 DLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAITEAGKT 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 440 YETVGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQEEADGIRKRCRVVGFALQA 519
Cdd:cd07668   86 YEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMSYALQA 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 677540546 520 EMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTLHMY 561
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 677540546   4 KARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 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 677540546 220 FICSVEDPTKQTKfkGIKSYISYKL-TPSNI------NSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEE-- 290
Cdd:cd06859    1 FEISVTDPVKVGD--GMSAYVVYRVtTKTNLpdfkksEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVkf 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 677540546 291 DFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06859   79 EFIEKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

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 677540546 222 CSVEDPtkQTKFKGIKSYISYKLTPSNINSP---VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKR 298
Cdd:cd06093    2 VSIPDY--EKVKDGGKKYVVYIIEVTTQGGEewtVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERRK 79

                         90       100
                 ....*....|....*....|....*
gi 677540546 299 RLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06093   80 QLEQYLQSLLNHPELRNSEELKEFL 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 677540546 220 FICSVEDPTKQTKFkgIKSYISYKLT-------PSNINSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDF 292
Cdd:cd06861    1 FEITVGDPHKVGDL--TSAHTVYTVRtrttspnFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 677540546 293 IEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06861   79 VEQRRAALEKMLRKIANHPVLQKDPDFRLFL 109

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 677540546 220 FICSVEDPTKQTKfKGIKSYISYKLTpSNINSP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATG 286
Cdd:cd06863    1 LECLVSDPQKELD-GSSDTYISYLIT-TKTNLPsfsrkefkVRRRYSDFVFLHECLSNDFPACVVPPLPDKHrleyiTGD 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 677540546 287 RFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06863   79 RFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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 677540546 223 SVEDPTKQtkFKGIKSYISY----KLTPSNINSPVY---RRYKHFDWLYNRLLHKFTVISVPHLPEKQAT----GRFEED 291
Cdd:cd06860    4 TVDNPEKH--VTTLETYITYrvttKTTRSEFDSSEYsvrRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVkgllDRFSPE 81

                         90       100       110
                 ....*....|....*....|....*....|..
gi 677540546 292 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06860   82 FVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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 677540546   3 LKARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11761    2 VTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

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 677540546 223 SVEDPTKQTKfkGIKSYISY----KLTPSNINSPVY---RRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 291
Cdd:cd07283    4 TVDDPKKHVC--TMETYITYrvttKTTRTEFDLPEYsvrRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSEE 81

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 677540546 292 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLCCR 326
Cdd:cd07283   82 FVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677540546 253 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQA--------TGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06864   48 LWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAmfmwqklsSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

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 677540546   4 KARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11911    1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTRVRKNNGDEGYVPTSYIEV 55

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. 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 677540546   4 KARALYNFQSENKEEISIQENEELVIFSENSLD-GWLQGQnSRGETGLFPASYVE 57
Cdd:cd11836    1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEpGWLAGE-LKGKTGWFPANYVE 54

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 677540546   5 ARALYNFQSENKEEISIQENEeLVIFSENSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11819    2 AKALYDYQAAEDNEISFVEGD-IITQIEQIDEGWWLGVNAKGQKGLFPANYVEL 54

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. 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 677540546   3 LKARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVE 57
Cdd:cd11997    2 VRVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains 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 677540546   6 RALYNFQSENKEEISIQENEELVIFSENSlDGWLQGqNSRGETGLFPASYVE 57
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQD-DGWWLG-ELNGKKGIFPATYVE 52

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 1 and 2; 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 SNX1, SNX2, and similar proteins. 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 efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. 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 677540546 350 LTIQIPTEHQDLQDVEDRVDAFKAFSKKMDDSVLQLTNVASELVrKHVGGFRKEFQKLGNAFQaishsfhmdppysSDAL 429
Cdd:cd07623    3 ITIKMDETDQWFEEKQQQIENLDQQLRKLHASVESLVNHRKELA-LNTGSFAKSAAMLSNCEE-------------HTSL 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 430 NNAISHTGKTYETVGEMFAEQPKNDLFLMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQ-----------RMSDEGRM 498
Cdd:cd07623   69 SRALSQLAEVEEKIEQLHGEQADTDFYILAELLKDYIGLIGAIKDVFHERVKVWQNWQNAQqtltkkreakaKLELSGRT 148

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677540546 499 D-------------------QEEADGIRKrcrvvgfALQAEMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTL 558
Cdd:cd07623  149 DkldqaqqeikeweakvdrgQKEFEEISK-------TIKKEIERFEKNRVKDFKDIIIKYLESLLNTQQQLIKYWEAFL 220

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 677540546 224 VEDPTKQTKFKGiKSYISYKL---TPSNI----NSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFE-EDFIEK 295
Cdd:cd06898    4 VRDPRTHKEDDW-GSYTDYEIflhTNSMCftlkTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNnEGFIEE 82

                         90       100
                 ....*....|....*....|....*...
gi 677540546 296 RKRRLILWMDHMTSHPVLSQYEGFQHFL 323
Cdd:cd06898   83 RQQGLQDFLEKVLQTPLLLSDSRLHLFL 110

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. 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 677540546   4 KARALYNFQSENKEEISIQENEelVIFSENSLDG-WLQGQNSrGETGLFPASYVEI 58
Cdd:cd11781    1 KARALYPFKAQSAKELSLKKGD--IIYIRRQIDKnWYEGEHN-GRVGIFPASYVEI 53

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 677540546 253 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQY 316
Cdd:COG5391  175 VRRRYSDFESLHSILIKLLPLCAIPPLPSKKsnseyYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNY 243

Src Homology 3 domain of Formin Binding Protein 1-Like; FormiN Binding Protein 1-Like (FNBP1L), also known as Toca-1 (Transducer of Cdc42-dependent actin assembly), forms a complex with neural Wiskott-Aldrich syndrome protein (N-WASP). The FNBP1L/N-WASP complex induces the formation of filopodia and endocytic vesicles. FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens. It contains an N-terminal F-BAR domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of the related protein, 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 677540546   6 RALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd12072    4 KALYPFDGSNEGTLAMKEGEVLYIIEEDKGDGWTRARKQNGEEGYVPTSYIEI 56

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, 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 677540546   5 ARALYNFQSENKEEISIQENEelVIFSENSLD-GWLQGQnSRGETGLFPASYVEIL 59
Cdd:cd11803    3 CRALYDFEPENEGELGFKEGD--IITLTNQIDeNWYEGM-VNGQSGFFPVNYVEVL 55

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 677540546 372 KAFSKKMDDSVLQLTNVASELVrKHVGGFRKEFQKLGNAFQAISHSFHMdppySSDALNNAISHTGKTYETVGEMFAEQP 451
Cdd:cd07596   10 KDYILKLEEQLKKLSKQAQRLV-KRRRELGSALGEFGKALIKLAKCEEE----VGGELGEALSKLGKAAEELSSLSEAQA 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677540546 452 KNDLFLMLDTLSLYQGLLSNFPDII-------------------------HLQKGAFAKVKESQRMSDEGRMDQEEADGI 506
Cdd:cd07596   85 NQELVKLLEPLKEYLRYCQAVKETLddradalltlqslkkdlaskkaqleKLKAAPGIKPAKVEELEEELEEAESALEEA 164

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 677540546 507 RKRCRVVGFALQAEMNHFHERRVADFKRMMQSYLKQQIVFYQRVSQQLEKTL 558
Cdd:cd07596  165 RKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAWESLL 216

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. 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 677540546   6 RALYNFQSENKEEISIQENEELVIFSENSlDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11770    3 EALSDFQAEQEGDLSFKKGEVLRIISKRA-DGWWLAENSKGNRGLVPKTYLKV 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. 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 677540546   5 ARALYNFQSENKEEISIQENEELVIFSENSLDGWLQGQnSRGETGLFPASYVE 57
Cdd:cd11976    2 AKARYDFCARDRSELSLKEGDIIKILNKKGQQGWWRGE-IYGRVGWFPANYVE 53