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 111185509 273 WWCENLGMWKASITSGEVTEENGEQLPCYFVMVSLQEVG----GVETKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPS 348
Cdd:cd06878    1 RWCEHLGKWRANIQSAEVTVEDDKEVPLYVIVVHVSEVGlnedESISSGWVVTRKLSEFHDLHRKLKECSSWLKKVELPS 80

                         90       100
                 ....*....|....*....|....*..
gi 111185509 349 LSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:cd06878   81 LSKKWFKSIDKKFLDKSKNQLQKYLQF 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, 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 111185509 273 WWCENLGMWKASITSGEVTEENGEQLPCYFVMVSLQEVG----GVETKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPS 348
Cdd:cd06878    1 RWCEHLGKWRANIQSAEVTVEDDKEVPLYVIVVHVSEVGlnedESISSGWVVTRKLSEFHDLHRKLKECSSWLKKVELPS 80

                         90       100
                 ....*....|....*....|....*..
gi 111185509 349 LSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:cd06878   81 LSKKWFKSIDKKFLDKSKNQLQKYLQF 107

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 111185509   59 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNA-NKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCLV 135
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKAdPDEERLKKAKEIYNEFLAPGspKEINLDSDLREEIRENLE 81

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 111185509  136 GNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKL 171
Cdd:pfam00615  82 KEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  316 KNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:pfam00787   7 EEWSVRRRYSDFVELHKKLLRKFPSVIIPPLP--PKRWLGRYNEEFIEKRRKGLEQYLQR 64

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, 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 111185509 273 WWCENLGMWKASITSGEVTEENGEQLPCYFVMVSLQEVG----GVETKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPS 348
Cdd:cd06878    1 RWCEHLGKWRANIQSAEVTVEDDKEVPLYVIVVHVSEVGlnedESISSGWVVTRKLSEFHDLHRKLKECSSWLKKVELPS 80

                         90       100
                 ....*....|....*....|....*..
gi 111185509 349 LSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:cd06878   81 LSKKWFKSIDKKFLDKSKNQLQKYLQF 107

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 111185509   59 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNA-NKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCLV 135
Cdd:pfam00615   2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKAdPDEERLKKAKEIYNEFLAPGspKEINLDSDLREEIRENLE 81

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 111185509  136 GNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKL 171
Cdd:pfam00615  82 KEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains 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. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509 283 ASITSGEVTEENGEQLPCYFVMVSLQEVGGVEtKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDQKFM 362
Cdd:cd06873    7 AVIINTGIVKEHGKTYAVYAISVTRIYPNGQE-ESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFP--GKKTFNNLDRAFL 83

                         90
                 ....*....|...
gi 111185509 363 EKSKNQLNKFLQE 375
Cdd:cd06873   84 EKRRKMLNQYLQS 96

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 111185509 282 KASITSGEVTEENGEQLPCYFVMVSLQEvggveTKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDQKF 361
Cdd:cd06093    1 SVSIPDYEKVKDGGKKYVVYIIEVTTQG-----GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLP--PKKLFGNLDPEF 73

                         90
                 ....*....|....
gi 111185509 362 MEKSKNQLNKFLQE 375
Cdd:cd06093   74 IEERRKQLEQYLQS 87

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  63 LANTFYREHFGMYMERMDKRALISFWESVEHLKNAN--KNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCLVG-N 137
Cdd:cd07440    1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTssDEELKSKAKEIYDKYISKDapKEINIPESIREEIEENLEEpY 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 111185509 138 KGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEK 170
Cdd:cd07440   81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  59 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVESKE--ISVEKSLYKEIQQClVG 136
Cdd:cd08737   10 LDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPsaINLDSHSYEKTSQN-VK 88

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 111185509 137 NKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKLLI 173
Cdd:cd08737   89 DPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  57 LQFEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCL 134
Cdd:cd08705    7 FSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQEIYQEFLAPGapSWINIDSKTMEITLKNL 86

                         90       100       110
                 ....*....|....*....|....*....|....
gi 111185509 135 vGNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLY 168
Cdd:cd08705   87 -KDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIY 119

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  60 EDILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQClVGN 137
Cdd:cd08738   10 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGapSAINLDSKSYDKTTQN-VKD 88

                         90       100       110
                 ....*....|....*....|....*....|...
gi 111185509 138 KGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEK 170
Cdd:cd08738   89 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; 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 fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111185509 313 VETKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPSLSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:cd06897   24 LPLRSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFLSTSSNPKLVEERRVGLEAFLRA 86

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111185509  62 ILANTFYREHFGMYMERMDKRALISFWESVE---------------------HLKNANKNEIPQLVGEIYQNFFVE--SK 118
Cdd:cd08719    1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEgyrvsaeqqlselhlrqrggeHQRSDVYEMLRAAALNIYDQYLSEkaSP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111185509 119 EISVEKSLYKEIQQCL-VGNKGIEVFYKIQEDVYETLK--DRYYPSFIVSDLYEK 170
Cdd:cd08719   81 RVPLDDSLVKKLLNRLrNDTPSDLWFDDIQQKVFDIMQedERFYPAFKKSPAYVK 135

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111185509 318 WTVPRRLSEFQNLHRKLSECVPSLKKVQLPslsklPFKSI---DQKFMEKSKNQLNKFL 373
Cdd:cd07277   32 WNVYRRYSEFYELHKKLKKKFPVVRSFDFP-----PKKAIgnkDAKFVEERRKRLQVYL 85

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 111185509 293 ENGEQLPCYFVMVSlqeVGGVEtknWTVPRRLSEFQNLHRKLsecvpslkkVQLPSLSK--LPFKSI----DQKFMEKSK 366
Cdd:cd06875   12 ETVEGYTVYIIEVK---VGSVE---WTVKHRYSDFAELHDKL---------VAEHKVDKdlLPPKKLignkSPSFVEKRR 76

                 ....*....
gi 111185509 367 NQLNKFLQE 375
Cdd:cd06875   77 KELEIYLQT 85

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; 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. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111185509 315 TKNWTVPRRLSEFQNLHRKLSEcVPSLKK---VQLPS--LSKLPFKSIDQKFMEKSKNQLNKFLQE 375
Cdd:cd06893   48 LATHTVNRRFREFLTLQTRLEE-NPKFRKimnVKGPPkrLFDLPFGNMDKDKIEARRGLLETFLRQ 112