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 29568084 386 EAPDLDLIEIEQKCDAVGKFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLAAVFSSSGYQGETDLNDAIT 465
Cdd:cd07668   1 EAPDLDLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAIT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 466 EAGKTYEEIASLVAEQPKKDLHFLMECNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITPQDKQTMVKRVGTMS 545
Cdd:cd07668  81 EAGKTYEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMS 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 29568084 546 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 595
Cdd:cd07668 161 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 210

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 29568084   4 KARVMYDFAAEPGNNELTVTEGEIITVTNPNVGGGWLEGKNNKGEQGLVPTDYVEIL 60
Cdd:cd11898   1 KARVLYDFAAEPGNNELTVKEGEIITVTNPNVGGGWIEAKNSQGERGLVPTDYVEIV 57

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 29568084 386 EAPDLDLIEIEQKCDAVGKFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLAAVFSSSGYQGETDLNDAIT 465
Cdd:cd07668   1 EAPDLDLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAIT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 466 EAGKTYEEIASLVAEQPKKDLHFLMECNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITPQDKQTMVKRVGTMS 545
Cdd:cd07668  81 EAGKTYEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMS 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 29568084 546 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 595
Cdd:cd07668 161 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 210

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 250 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFGSAIPIPSLPDKQVTGRFEEEFIKMRME 329
Cdd:cd07285   1 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFGLAIPIPSLPDKQVTGRFEEEFIKMRME 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 29568084 330 RLQAWMTRMCRHPVVSESEVFQQFLNFRDEKEWKTGKRKAEKDELV 375
Cdd:cd07285  81 RLQAWMTRMCRHPVISESEVFQQFLNFRDEKEWKTGKRKAEKDETV 126

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084   275 TPTNTNRSVNHRYKHFDWLYERLLVKFGSAIpIPSLPDKQVTGRFEEEFIKMRMERLQAWMTRMCRHPVVSESEVFQQFL 354
Cdd:pfam00787   3 TFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

                  ...
gi 29568084   355 NFR 357
Cdd:pfam00787  82 ESD 84

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 29568084      4 KARVMYDFAAEpGNNELTVTEGEIITVTNpNVGGGWLEGKNNKGEQGLVPTDYVE 58
Cdd:smart00326   4 QVRALYDYTAQ-DPDELSFKKGDIITVLE-KSDDGWWKGRLGRGKEGLFPSNYVE 56

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 29568084     6 RVMYDFAAEPGNnELTVTEGEIITVTNpNVGGGWLEGKNNKGEQGLVPT 54
Cdd:pfam00018   1 VALYDYTAQEPD-ELSFKKGDIIIVLE-KSEDGWWKGRNKGGKEGLIPS 47

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 29568084 386 EAPDLDLIEIEQKCDAVGKFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLAAVFSSSGYQGETDLNDAIT 465
Cdd:cd07668   1 EAPDLDLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAIT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 466 EAGKTYEEIASLVAEQPKKDLHFLMECNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITPQDKQTMVKRVGTMS 545
Cdd:cd07668  81 EAGKTYEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMS 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 29568084 546 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 595
Cdd:cd07668 161 YALQAEMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRFPVM 210

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 29568084 394 EIEQKCDAVGKFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLAAVFSSSGYQGETDLNDAITEAGKTYEE 473
Cdd:cd07626   1 DVEQQVDAFKKFVKSMDDSVKNLINIAQEQAKKHQGPYKKEYQKIGQAFTSLGTAFELDETPTSVPLTQAIKHTGQAYEE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 474 IASLVAEQPKKDLHFLMECNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITPQDKQTMVKRVGTMSYALQAEMN 553
Cdd:cd07626  81 IGELFAEQPKHDLIPLLDGLHEYKGLLSTFPDIIGVHKGAVQKVKECERLVDEGKMSSAELEEVKRRTDVISYALLAEIN 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 29568084 554 HFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRF 592
Cdd:cd07626 161 HFHRERVRDFKSMMRNYLQQQIEFYQKIAAKLEEALAMY 199

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 250 FDCVVADPRKGSKMYGLKSYIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFgSAIPIPSLPDKQVTGRFEEEFIKMRME 329
Cdd:cd06862   1 YHCTVTNPKKESKFKGLKSFIAYQITPTHTNVTVSRRYKHFDWLYERLVEKY-SCIAIPPLPEKQVTGRFEEDFIEKRRE 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 29568084 330 RLQAWMTRMCRHPVVSESEVFQQFLNFRDEKEWKTGKRKAEKDELV 375
Cdd:cd06862  80 RLELWMNRLARHPVLSQSEVFRHFLTCTDEKDWKSGKRKAEKDELV 125

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 29568084 391 DLIEIEQKCDAVGKFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLAAVFSSSGYQGETDLNDAITEAGKT 470
Cdd:cd07669   6 DLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAISHTGRT 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 471 YEEIASLVAEQPKKDLHFLMECNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITPQDKQTMVKRVGTMSYALQA 550
Cdd:cd07669  86 YEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVGFALQA 165

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 29568084 551 EMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQAL 589
Cdd:cd07669 166 EMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTL 204

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 29568084   4 KARVMYDFAAEPGNNELTVTEGEIITVTNPNVGGGWLEGKNNKGEQGLVPTDYVEIL 60
Cdd:cd11898   1 KARVLYDFAAEPGNNELTVKEGEIITVTNPNVGGGWIEAKNSQGERGLVPTDYVEIV 57

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084   275 TPTNTNRSVNHRYKHFDWLYERLLVKFGSAIpIPSLPDKQVTGRFEEEFIKMRMERLQAWMTRMCRHPVVSESEVFQQFL 354
Cdd:pfam00787   3 TFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

                  ...
gi 29568084   355 NFR 357
Cdd:pfam00787  82 ESD 84

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 29568084 265 GLKSYIEYQLTPTNTN---RSVNHRYKHFDWLYERLLVKFGSaIPIPSLPDKQVTGRFEEEFIKMRMERLQAWMTRMCRH 341
Cdd:cd06093  13 GGKKYVVYIIEVTTQGgeeWTVYRRYSDFEELHEKLKKKFPG-VILPPLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNH 91

                        90
                ....*....|...
gi 29568084 342 PVVSESEVFQQFL 354
Cdd:cd06093  92 PELRNSEELKEFL 104

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 29568084 250 FDCVVADPRK-GSkmyGLKSYIEYQL-TPTNT------NRSVNHRYKHFDWLYERLLVKFGSAIpIPSLPDKQVTGRFEE 321
Cdd:cd06859   1 FEISVTDPVKvGD---GMSAYVVYRVtTKTNLpdfkksEFSVLRRYSDFLWLYERLVEKYPGRI-VPPPPEKQAVGRFKV 76

                        90       100       110
                ....*....|....*....|....*....|....*
gi 29568084 322 --EFIKMRMERLQAWMTRMCRHPVVSESEVFQQFL 354
Cdd:cd06859  77 kfEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

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 29568084 254 VADPRKGSKmyGLKSYIEYQLTpTNTNR--------SVNHRYKHFDWLYERLLVKFGSAIpIPSLPDKQVT----GRFEE 321
Cdd:cd06860   5 VDNPEKHVT--TLETYITYRVT-TKTTRsefdsseySVRRRYQDFLWLRQKLEESHPTHI-IPPLPEKHSVkgllDRFSP 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 29568084 322 EFIKMRMERLQAWMTRMCRHPVVSESEVFQQFL 354
Cdd:cd06860  81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first 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 29568084   4 KARVMYDFAAEpGNNELTVTEGEIITVTNPNVGGGWLEGKNNKGEQGLVPTDYVEI 59
Cdd:cd11912   1 TAKVLYDYTAS-GDDEVSISEGEEVTVLEPDDGSGWTKVRNGSGEEGLVPTSYIEI 55

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 406 TKAMDDGVKELLTVGQEHWKRCTGpLPKEYQKIGKALQSLAAVFSSSGyqgETDLNDAITEAGKTYEEIASLVAEQPKKD 485
Cdd:cd07307   2 LDELEKLLKKLIKDTKKLLDSLKE-LPAAAEKLSEALQELGKELPDLS---NTDLGEALEKFGKIQKELEEFRDQLEQKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 486 LHFLMECNHEY-KGFLGCFPDIIGAHKG-------AIEKVKESDKLVATSKI---TPQDKQTMVKRVGTMSYALQAEMNH 554
Cdd:cd07307  78 ENKVIEPLKEYlKKDLKEIKKRRKKLDKarldydaAREKLKKLRKKKKDSSKlaeAEEELQEAKEKYEELREELIEDLNK 157

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 29568084 555 FHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALS 590
Cdd:cd07307 158 LEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLP 193

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins 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, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 29568084   4 KARVMYDFAAEpGNNELTVTEGEIITVTNpNVGGGWLEGKNNKGEQGLVPTDY 56
Cdd:cd00174   1 YARALYDYEAQ-DDDELSFKKGDIITVLE-KDDDGWWEGELNGGREGLFPANY 51

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 29568084 254 VADPRKgsKMYGLKSYIEYQLTpTNTNR--------SVNHRYKHFDWLYERLLVKFGSAIpIPSLPDK----QVTGRFEE 321
Cdd:cd07283   5 VDDPKK--HVCTMETYITYRVT-TKTTRtefdlpeySVRRRYQDFDWLRNKLEESQPTHL-IPPLPEKfvvkGVVDRFSE 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 29568084 322 EFIKMRMERLQAWMTRMCRHPVVSESEVFQQFLN 355
Cdd:cd07283  81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFLT 114

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 253 VVADPRK----GSKMYGLKSYIEYQLT-----PTNTNR--SVNHRYKHFDWLYERLLVKFGSAIpIPSLPDKQV---TGR 318
Cdd:cd06865   3 TVSDPKKeqepSRVPLGGPPYISYKVTtrtniPSYTHGefTVRRRFRDVVALADRLAEAYRGAF-VPPRPDKSVvesQVM 81

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 29568084 319 FEEEFIKMRMERLQAWMTRMCRHPVVSESEVFQQFL 354
Cdd:cd06865  82 QSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFL 117

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 127 SRTDGTSAQRNSSANNWDTGFGHPQAYQGPATgdddewdedwdDPKSSSPYFKDSEPAEAGGIQRGNSRAgASSMKLPLN 206
Cdd:COG5391   1 NSPDASSSPKNESSASDSGPSGSSSESQESST-----------VKNNDGSPVNSSIKSTPLDIQKRYSGF-ESSAKLPRI 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 207 KFPGFAKPGM----EQYLLAKQ------LAKPKEKIAI-IVGDYGPMWVYPTST--------FDCVVADPRK-GSKMYGL 266
Cdd:COG5391  69 SDAPSFVPPPgghtISYTIAIHdskihsRASEFRSLRDmLSLLLPTSLQPPLSTshtildyfISSTVSNPQSlTLLVDSR 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29568084 267 KSYIEYQLTPTNTNRS----------VNHRYKHFDWLYERLLVKFGSaIPIPSLPDKQVT-----GRFEEEFIKMRMERL 331
Cdd:COG5391 149 DKHTSYEIITVTNLPSfqlresrplvVRRRYSDFESLHSILIKLLPL-CAIPPLPSKKSNseyygDRFSDEFIEERRQSL 227

                       250       260
                ....*....|....*....|....*.
gi 29568084 332 QAWMTRMCRHPVVSESEVFQQFLNFR 357
Cdd:COG5391 228 QNFLRRVSTHPLLSNYKNSKSWESHS 253

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 29568084   4 KARVMYDFAAEpGNNELTVTEGEIITVTNPNVGGGWLEGKNNkGEQGLVPTDYVEI 59
Cdd:cd11882   1 RARALYACKAE-DESELSFEPGQIITNVQPSDEPGWLEGTLN-GRTGLIPENYVEF 54

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 29568084 261 SKMYGLKSYIEYqlTPTNTNRSVNHRYKHFDWLYErLLVKFGSAIPIPSLPDKQ---------VTGRFEEEFIKMRMERL 331
Cdd:cd06867  10 SSEGGSGSYIVY--VIRLGGSEVKRRYSEFESLRK-NLTRLYPTLIIPPIPEKHslkdyakkpSKAKNDAKIIERRKRML 86

                        90       100
                ....*....|....*....|....
gi 29568084 332 QAWMTRMCRHPVVSESEVFQQFLN 355
Cdd:cd06867  87 QRFLNRCLQHPILRNDIVFQKFLD 110

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 29568084   5 ARVMYDFAAEpGNNELTVTEGEIITVTNpNVGGGWLEGKNNKGEQGLVPTDYVEI 59
Cdd:cd11819   2 AKALYDYQAA-EDNEISFVEGDIITQIE-QIDEGWWLGVNAKGQKGLFPANYVEL 54

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 29568084   5 ARVMYDFAAE-PGnnELTVTEGEIITVTNpNVGGGWLEGKNNkGEQGLVPTDYVEIL 60
Cdd:cd11803   3 CRALYDFEPEnEG--ELGFKEGDIITLTN-QIDENWYEGMVN-GQSGFFPVNYVEVL 55

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. 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 29568084   4 KARVMYDFAAEPGN-NELTVTEGEIITVTNpnVGGGWLEGKNNKGEQGLVPTDYVEI 59
Cdd:cd11855   1 RARALYPYDASPDDpNELSFEKGEILEVSD--TSGKWWQARKSNGETGICPSNYLQL 55

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 29568084   6 RVMYDFaaePGNNE--LTVTEGEIITVTNPNVGGGWLEGKNNKGEQGLVPTDYVEI 59
Cdd:cd12072   4 KALYPF---DGSNEgtLAMKEGEVLYIIEEDKGDGWTRARKQNGEEGYVPTSYIEI 56

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. 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 29568084   4 KARVMYDF-AAEpgNNELTVTEGEIITVT---NPNvgggWLEGKNNKGEqGLVPTDYV 57
Cdd:cd11820   2 KVRALYDFeAAE--DNELTFKAGEIITVLddsDPN----WWKGSNHRGE-GLFPANFV 52

Variant 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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 29568084     4 KARVMYDFAAePGNNELTVTEGEIITVTNPNVGGGWlEGKNNkGEQGLVPTDYVEIL 60
Cdd:pfam07653   1 YGRVIFDYVG-TDKNGLTLKKGDVVKVLGKDNDGWW-EGETG-GRVGLVPSTAVEEI 54

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second 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 29568084   7 VMYDFAAEpGNNELTVTEGEIITVTNPNVGGGWLEGKNNkGEQGLVPTDY 56
Cdd:cd11778   4 ALYDYEAQ-GDDEISIRVGDRIAVIRGDDGSGWTYGEIN-GVKGLFPTSY 51