The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; 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. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 214 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 293
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918930 294 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 336
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 457 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 530
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918930 531 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 561
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; 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. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 214 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 293
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918930 294 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 336
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 457 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 530
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918930 531 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 561
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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 1182918930  254 VGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNY---EFLKSKREEFQEYLQKLLQHPELSN-SQLL 329
Cdd:smart00312  21 TKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNfseEFIEKRRRGLEKYLQSLLNHPELINhSEVV 100

                   ....*
gi 1182918930  330 ADFLS 334
Cdd:smart00312 101 LEFLE 105

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930   3 FLKQEGAVHVLQFCLTVEEFNDRILRPELSNDemlslheeLQKIYKTYCLDESIDKIRFDPFIVEEIQriaegpyiDVVK 82
Cdd:pfam00615  18 FLESEFSEENLEFWLACEEFKKADPDEERLKK--------AKEIYNEFLAPGSPKEINLDSDLREEIR--------ENLE 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1182918930  83 LQTMRCLFEAY-EHVLSLLENVFTPMFCHSDeYFRQL 118
Cdd:pfam00615  82 KEPTRDLFDEAqAEVYELMEKDSYPRFLKSP-LYLRL 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; 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. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 214 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 293
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918930 294 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 336
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 457 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 530
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918930 531 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 561
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 231 ERKEKKERIPVFCIDVERNDrravghePEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEF 310
Cdd:cd06093     9 KVKDGGKKYVVYIIEVTTQG-------GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERRKQL 81

                          90       100
                  ....*....|....*....|....
gi 1182918930 311 QEYLQKLLQHPELSNSQLLADFLS 334
Cdd:cd06093    82 EQYLQSLLNHPELRNSEELKEFLE 105

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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 1182918930 216 KISIpyVDFFEDPSSERKEkkerIPVFCIDVER--NDRRAVGhepehWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 293
Cdd:cd06876    21 RVSI--QSYISDVEEEGKE----FVVYLIEVQRlnNDDQSSG-----WVVARRYSEFLELHKYLKKRYPGVLKLDFPQKR 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918930 294 IIGPKNYE--FLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 334
Cdd:cd06876    90 KISLKYSKtlLVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 231 ERKEKKERIPVFCIDVERNdrravghEPEHWSVYRRYLEFYVLESKLTEfhgAFPDAQ--LPSKRIIGPK-NYEFLKSKR 307
Cdd:cd07276    12 EVMEERARFTVYKIRVENK-------VGDSWFVFRRYTDFVRLNDKLKQ---MFPGFRlsLPPKRWFKDNfDPDFLEERQ 81

                          90       100
                  ....*....|....*....|....*.
gi 1182918930 308 EEFQEYLQKLLQHPELSNSQLLADFL 333
Cdd:cd07276    82 LGLQAFVNNIMAHKDIAKCKLVREFF 107

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 1182918930 242 FCIDVERndrravGHEPEH-WSVYRRYLEFYVLESKLtEFHGAfpDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQH 320
Cdd:cd06871    24 YIIRVQR------GPSPENsWQVIRRYNDFDLLNASL-QISGI--SLPLPPKKLIGNMDREFIAERQQGLQNYLNVILMN 94

                          90       100
                  ....*....|....*....|....
gi 1182918930 321 PELSNSQLLADFLSPNGGETQFLD 344
Cdd:cd06871    95 PILASCLPVKKFLDPNNYSANFTE 118

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 229 SSERKEKKERIPVFCIDVerndrrAVGHEpeHWSVYRRYLEFYVLESKLTEfhgAFPDAQL--PSKRIIGpKNY--EFLK 304
Cdd:cd06870    10 SDEDREKKKRFTVYKVVV------SVGRS--SWFVFRRYAEFDKLYESLKK---QFPASNLkiPGKRLFG-NNFdpDFIK 77

                          90       100
                  ....*....|....*....|....*....
gi 1182918930 305 SKREEFQEYLQKLLQHPELSNSQLLADFL 333
Cdd:cd06870    78 QRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1182918930 263 VYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGP-KNYEFLKSKREEFQEYLQKLLQHPE-LSNSQL 328
Cdd:cd06898    39 VRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRfNNEGFIEERQQGLQDFLEKVLQTPLlLSDSRL 106

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 1182918930 262 SVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIgpKNY--EFLKSKREE---------FQEYLQKLLQHPELSNSQLLA 330
Cdd:cd06867    29 EVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSL--KDYakKPSKAKNDAkiierrkrmLQRFLNRCLQHPILRNDIVFQ 106

                  ....*.
gi 1182918930 331 DFLSPN 336
Cdd:cd06867   107 KFLDPN 112

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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 1182918930 234 EKKERIPVFCIDVERNDRRavghepehWSVYRRYLEFYVLESKLTEFHGAFPDAqLPSKRIIGPKNYEFLKSKREEFQEY 313
Cdd:cd06875    12 ETVEGYTVYIIEVKVGSVE--------WTVKHRYSDFAELHDKLVAEHKVDKDL-LPPKKLIGNKSPSFVEKRRKELEIY 82

                          90       100       110
                  ....*....|....*....|....*....|
gi 1182918930 314 LQKLLQHPELSNSQLLADFLSPNGGETQFL 343
Cdd:cd06875    83 LQTLLSFFQKTMPRELAHFLDFHKYEIIGL 112

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1182918930 262 SVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 334
Cdd:cd06862    33 TVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFRHFLT 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 259 EHWSVYRRYLEFYVLESKLTEFHG--AFPDAQLPSKRIIG----------PKNYEFLKSKREEFQEYLQKLLQHPELSNS 326
Cdd:cd07281    35 KHFTVKRRFSDFLGLYEKLSEKHSqnGFIVPPPPEKSLIGmtkvkvgkedSSSAEFLERRRAALERYLQRIVSHPSLLQD 114

                  ....*..
gi 1182918930 327 QLLADFL 333
Cdd:cd07281   115 PDVREFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 241 VFCIDVERNDRRAVghepehwsVYRRYLEFYVLESKLTEFHGAfPDaqLPSKRIIGpKNYEFLKSKREEFQEYLQKLLQH 320
Cdd:cd06880    21 VFTIEVLVNGRRHT--------VEKRYSEFHALHKKLKKSIKT-PD--FPPKRVRN-WNPKVLEQRRQGLEAYLQGLLKI 88

                          90
                  ....*....|...
gi 1182918930 321 PELsnSQLLADFL 333
Cdd:cd06880    89 NEL--PKQLLDFL 99

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930   3 FLKQEGAVHVLQFCLTVEEFNDRILRPELSNDemlslheeLQKIYKTYCLDESIDKIRFDPFIVEEIQriaegpyiDVVK 82
Cdd:pfam00615  18 FLESEFSEENLEFWLACEEFKKADPDEERLKK--------AKEIYNEFLAPGSPKEINLDSDLREEIR--------ENLE 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1182918930  83 LQTMRCLFEAY-EHVLSLLENVFTPMFCHSDeYFRQL 118
Cdd:pfam00615  82 KEPTRDLFDEAqAEVYELMEKDSYPRFLKSP-LYLRL 117

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 231 ERKEKKERIPVFCIDVERNDRravgHEPEHwsVYRRYLEFYVLESKLTEfhgAFPDAQLPS---KRIIGPKNYEFLKSKR 307
Cdd:cd06883     8 QKRYSPEKYYIYVVKVTRENQ----TEPSF--VFRTFEEFQELHNKLSL---LFPSLKLPSfpaRVVLGRSHIKQVAERR 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1182918930 308 -EEFQEYLQKLLQHP-ELSNSQLLADFLSP 335
Cdd:cd06883    79 kIELNSYLKSLFNASpEVAESDLVYTFFHP 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 261 WSVYRRYLEFYVLESKLTE--FHGAFPDAQLPSKRIIG----------PKNYEFLKSKREEFQEYLQKLLQHPELSNSQL 328
Cdd:cd07282    37 FSVRRRFSDFLGLHSKLASkyLHVGYIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPD 116

                  ....*
gi 1182918930 329 LADFL 333
Cdd:cd07282   117 LRQFL 121

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1182918930 261 WSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPK----NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 334
Cdd:cd07284    37 FEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMverfNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 114

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1182918930 260 HWSVyrRYLEFYVLESKLTEFHGAFPDAQLPSKRIIgPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFL 333
Cdd:cd06885    30 HCSV--RYSQLHGLNEQLKKEFGNRKLPPFPPKKLL-PLTPAQLEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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 1182918930 263 VYRRYLEFYVLESKLTEfhgAFPDA------QLPSKRIIGPK----NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADF 332
Cdd:cd07280    41 AYKRYSEFVQLREALLD---EFPRHkrneipQLPPKVPWYDSrvnlNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEF 117

                  ...
gi 1182918930 333 LSP 335
Cdd:cd07280   118 LLP 120

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. 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 Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930 259 EHWSVYRRYLEFYVLESKLTEfhgAFPD--AQLPSKRIIGP-------KNYEFLKSKR-EEFQEYLQKLLQHPE-LSNSQ 327
Cdd:cd06890    27 KTRYLCRYYQDFYKLHIALLD---LFPAeaGRNSSKRILPYlpgpvtdVVNDSISLKRlNDLNEYLNELINLPAyIQTSE 103

                  ....*...
gi 1182918930 328 LLADFLSP 335
Cdd:cd06890   104 VVRDFFAN 111

Regulator of G protein signaling (RGS) domain 2 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring protein), a member of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the second RGS domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918930   1 MNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELqKIYKTYCLDESI------DKIRFDpfIVEEIQRiAE 74
Cdd:cd08721    12 MEYMEQEGARNLLQFWLAADNFQSQLAAKEGQYDGQQAQNDAM-IIYDKYFSLQATeplgfdDKTRLE--VESNICR-EG 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1182918930  75 GPYIDvvklqtmrCLFEAYEHVLSLLENVFTPMFCHSDEYFR 116
Cdd:cd08721    88 GPLPS--------CFEAPLLQALTTLEQHYLPGFLSSQLYYK 121