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 66793416 365 PTEHQDLQDVEDRVDTFKAFSKKMDDSVLQLSNVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSDALNNAIS 444
Cdd:cd07669   1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 445 HTGRTYETVGEMFAEQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669  81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 66793416 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLHMY 571
Cdd:cd07669 161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66793416   4 KGRALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVEI 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 66793416 365 PTEHQDLQDVEDRVDTFKAFSKKMDDSVLQLSNVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSDALNNAIS 444
Cdd:cd07669   1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 445 HTGRTYETVGEMFAEQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669  81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 66793416 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLHMY 571
Cdd:cd07669 161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 230 FACSIEDPTKQTKFKGIKSYISYKLTPTHAGSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 309
Cdd:cd07286   1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 66793416 310 LILWMDHMTSHPVLSQYEGFQHFLSC--LDDKQWKMGKRRAEKDEMV 354
Cdd:cd07286  81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 66793416   263 VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

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 66793416    240 QTKFKGIKSYISYKLTptHAGSP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGR---FEEDFIEKRKRRLIL 312
Cdd:smart00312   5 EKIGDGKHYYYVIEIE--TKTGLeewtVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnFSEEFIEKRRRGLEK 82

                           90       100
                   ....*....|....*....|...
gi 66793416    313 WMDHMTSHPVLSQ-YEGFQHFLS 334
Cdd:smart00312  83 YLQSLLNHPELINhSEVVLEFLE 105

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 66793416     7 ALYDFHSENKEEISIQQDEELVIFSETSlDGWLQGQNsRGETGLFPASYVE 57
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESE-DGWWEGIN-TGRTGLVPANYVE 49

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 33; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 365 PTEHQDLQDVEDRVDTFKAFSKKMDDSVLQLSNVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSDALNNAIS 444
Cdd:cd07669   1 PTEHQDLQDVEERVDVFKAFSKKMDDSVLQLSNVASELVRKHLGGFRKEFQKLGNAFQAISHSFQLDPPYSSEALNNAIS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 445 HTGRTYETVGEMFAEQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVG 524
Cdd:cd07669  81 HTGRTYEAVGEMFAEQPKNDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMDQDEADGIRKRCRVVG 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 66793416 525 FALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLHMY 571
Cdd:cd07669 161 FALQAEMNHFHQRRELDFKQMMQHYLRQQIIFYQRVSQQLEKTLRMY 207

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 9 and Similar Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. This subfamily consists of SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 373 DVEDRVDTFKAFSKKMDDSVLQLSNVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSDALNNAISHTGRTYET 452
Cdd:cd07626   1 DVEQQVDAFKKFVKSMDDSVKNLINIAQEQAKKHQGPYKKEYQKIGQAFTSLGTAFELDETPTSVPLTQAIKHTGQAYEE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 453 VGEMFAEQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVGFALQAEMN 532
Cdd:cd07626  81 IGELFAEQPKHDLIPLLDGLHEYKGLLSTFPDIIGVHKGAVQKVKECERLVDEGKMSSAELEEVKRRTDVISYALLAEIN 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 66793416 533 HFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLHMY 571
Cdd:cd07626 161 HFHRERVRDFKSMMRNYLQQQIEFYQKIAAKLEEALAMY 199

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 230 FACSIEDPTKQTKFKGIKSYISYKLTPTHAGSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRR 309
Cdd:cd07286   1 FQCTIDDPTKQTKFKGMKSYISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKG 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 66793416 310 LILWMDHMTSHPVLSQYEGFQHFLSC--LDDKQWKMGKRRAEKDEMV 354
Cdd:cd07286  81 LIWWMDHMCSHPVLARCDAFQHFLTCpsTDEKAWKQGKRKAEKDEMV 127

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 9; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 370 DLQDVEDRVDTFKAFSKKMDDSVLQLSNVAAELVRKHVGGFRKEFQKLGSAFQAISHAFQMDPPFRSDALNNAISHTGRT 449
Cdd:cd07668   6 DLVEIEQKCEAVGRFTKAMDDGVKELLTVGQEHWKRCTGPLPKEYQKIGKALQSLATVFSTSGYQGETDLNDAITEAGKT 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 450 YETVGEMFAEQPKHDLFQMLDTLSLYQGLLSNFPDIIHLQKGAFAKVKESQRMSDEGRMAQEEADGIRRRCRVVGFALQA 529
Cdd:cd07668  86 YEEIASLVAEQPKKDLHFLMETNHEYKGFLGCFPDIIGAHKGAIEKVKESDKLVATSKITLQDKQNMVKRVSTMSYALQA 165

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 66793416 530 EMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTLHMY 571
Cdd:cd07668 166 EMNHFHSNRIYDYNSVIRLYLEQQVQFYETIAEKLRQALSRF 207

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66793416   4 KGRALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVEI 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 66793416 233 SIEDPTKQTKfkGIKSYISYKLT-----PTHAGSP--VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEE--DFI 303
Cdd:cd06859   4 SVTDPVKVGD--GMSAYVVYRVTtktnlPDFKKSEfsVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVkfEFI 81

                        90       100       110
                ....*....|....*....|....*....|
gi 66793416 304 EKRKRRLILWMDHMTSHPVLSQYEGFQHFL 333
Cdd:cd06859  82 EKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66793416   4 KGRALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11897   1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVEV 55

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 230 FACSIEDPTKQTKFkgIKSYISYKL---TPTHAGSP----VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDF 302
Cdd:cd06861   1 FEITVGDPHKVGDL--TSAHTVYTVrtrTTSPNFEVssfsVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 66793416 303 IEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd06861  79 VEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

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 66793416 230 FACSIEDPTKQTKfKGIKSYISYKLTpTHAGSP--------VYRRYKHFDWLYNRLLHKFTVISVPHLPEKQ-----ATG 296
Cdd:cd06863   1 LECLVSDPQKELD-GSSDTYISYLIT-TKTNLPsfsrkefkVRRRYSDFVFLHECLSNDFPACVVPPLPDKHrleyiTGD 78

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 66793416 297 RFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd06863  79 RFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLE 116

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 66793416 260 GSPVYRRYKHFDWLYNRLLHKFTVISVPHLPEKQATGRFEEDFIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd06866  29 KSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLT 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 233 SIEDPTKQTKfkGIKSYISY----KLTPTHAGSPVY---RRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 301
Cdd:cd07283   4 TVDDPKKHVC--TMETYITYrvttKTTRTEFDLPEYsvrRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSEE 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 66793416 302 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd07283  82 FVETRRKALDKFLKRIADHPVLSFNEHFNVFLT 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX7 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, SNX30, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX7 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 233 SIEDPtkQTKFKGIKSYISYKL-TPTHAGS------PVYRRYKHFDWLYNRLLHKFTVISVPHLPEK----QATGRFEED 301
Cdd:cd07284   4 TVDEP--ESHVTAIETFITYRVmTKTSRSEfdssefEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKfvmkGMVERFNED 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 66793416 302 FIEKRKRRLILWMDHMTSHPVLSQYEGFQHFLS 334
Cdd:cd07284  82 FIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 114

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSLD-GWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11767   3 VALYPFTGENDEELSFEKGERLEIIEKPEDDpDWWKARNALGTTGLVPRNYVEV 56

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 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVE 57
Cdd:cd11997   5 RALYDYTGQEADELSFKAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56

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 66793416   4 KGRALYDFHSE-NKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVEIV 59
Cdd:cd11898   1 KARVLYDFAAEpGNNELTVKEGEIITVTNPNVGGGWIEAKNSQGERGLVPTDYVEIV 57

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 66793416 382 KAFSKKMDDSVLQLSNVAAELVrKHVGGFRKEFQKLGSAFQAISHAFQMdppfRSDALNNAISHTGRTYETVGEMFAEQP 461
Cdd:cd07596  10 KDYILKLEEQLKKLSKQAQRLV-KRRRELGSALGEFGKALIKLAKCEEE----VGGELGEALSKLGKAAEELSSLSEAQA 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 462 KHDLFQMLDTLSLYQGLLSNFPDII-------------------------HLQKGAFAKVKESQRMSDEGRMAQEEADGI 516
Cdd:cd07596  85 NQELVKLLEPLKEYLRYCQAVKETLddradalltlqslkkdlaskkaqleKLKAAPGIKPAKVEELEEELEEAESALEEA 164

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 66793416 517 RRRCRVVGFALQAEMNHFHQRRELDFKHMMQSYLRQQILFYQRVGQQLEKTL 568
Cdd:cd07596 165 RKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAWESLL 216

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 66793416   6 RALYDFHSENKEEISIQQDEeLVIFSETSLDGWLQGQNSRGETGLFPASYVEI 58
Cdd:cd11819   3 KALYDYQAAEDNEISFVEGD-IITQIEQIDEGWWLGVNAKGQKGLFPANYVEL 54

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 66793416   4 KGRALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSrGETGLFPASYVEI 58
Cdd:cd11882   1 RARALYACKAEDESELSFEPGQIITNVQPSDEPGWLEGTLN-GRTGLIPENYVEF 54

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQNSRGETGLFPASYVE 57
Cdd:cd11998   4 RALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVE 55

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 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSlDGWLQGqNSRGETGLFPASYVE 57
Cdd:cd11823   3 KALYSYTANREDELSLQPGDIIEVHEKQD-DGWWLG-ELNGKKGIFPATYVE 52

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 66793416     6 RALYDFHSENKEEISIQQDEELVIFSEtSLDGWLQGQNSRGETGLFPA 53
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEK-SEDGWWKGRNKGGKEGLIPS 47

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. 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 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSLDGWLQGQnSRGETGLFPASYVE 57
Cdd:cd11843   3 RALYDYEGQESDELSFKAGDILTKLEEEDEQGWCKGR-LDGRVGLYPANYVE 53

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 66793416 261 SPVYRRYKHFDWLYNRLlHKFTVISVPHLPEK---------QATGRFEEDFIEKRKRRLILWMDHMTSHPvLSQYE 327
Cdd:cd06894  38 SSVRRRYSDFEWLRSEL-ERDSKIVVPPLPGKalkrqlpfrGDDGIFEEEFIEERRKGLETFINKVAGHP-LAQNE 111

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 66793416   6 RALYDFHSENKEEISIQQDEELVIFSETSlDGWLQGQnSRGETGLFPASYVEIV 59
Cdd:cd11803   4 RALYDFEPENEGELGFKEGDIITLTNQID-ENWYEGM-VNGQSGFFPVNYVEVL 55

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 244 KGIKSYISYKLTPT---HAGSPV--YRRYKHFDWLYNRLLHKF---TVISVPHLPEK----QATGRFEEDFIEKRKRRLI 311
Cdd:cd07280  17 TGGGAYVVWKITIEtkdLIGSSIvaYKRYSEFVQLREALLDEFprhKRNEIPQLPPKvpwyDSRVNLNKAWLEKRRRGLQ 96

                        90       100
                ....*....|....*....|..
gi 66793416 312 LWMDHMTSHPVLSQYEGFQHFL 333
Cdd:cd07280  97 YFLNCVLLNPVFGGSPVVKEFL 118

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, 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 66793416   6 RALYDFHSENKEEISIqQDEELVIFSETSLDGWLQGQNSR-GETGLFPASYVEIV 59
Cdd:cd11934   6 RAVYDYNAADEDEVSF-QDGDTIVNVQQIDDGWMYGTVERtGDTGMLPANYVEAI 59

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 66793416   4 KGRALYDFHSENKEEISIQQDEelVIFSETSLDG-WLQGQNSrGETGLFPASYVEI 58
Cdd:cd11781   1 KARALYPFKAQSAKELSLKKGD--IIYIRRQIDKnWYEGEHN-GRVGIFPASYVEI 53

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66793416 229 PFACSIEdptkqtKFKGIKSYISYKLTPTHAGSP-----VYRRYKHFDWLYNRLlhKFTVISVPhLPEKQATGRFEEDFI 303
Cdd:cd06871   7 PLTCVIE------ASQNIQSHTEYIIRVQRGPSPenswqVIRRYNDFDLLNASL--QISGISLP-LPPKKLIGNMDREFI 77