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 1160595254  13 LLDDTVPLTAAIEASQSLQSHTEYIIRVQRGISVENSWQIVRRYSDFDLLNNSLQIAGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1160595254  93 QKGLQNYLNVITTNHILSNCELVKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120

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 1160595254  13 LLDDTVPLTAAIEASQSLQSHTEYIIRVQRGISVENSWQIVRRYSDFDLLNNSLQIAGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1160595254  93 QKGLQNYLNVITTNHILSNCELVKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120

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 1160595254   32 SHTEYIIRVQRGISVEnSWQIVRRYSDFDLLNNSLQ--IAGLSLP-LPPKKLIG---NMDREFIAERQKGLQNYLNVITT 105
Cdd:smart00312  11 KHYYYVIEIETKTGLE-EWTVSRRYSDFLELHSKLKkhFPRSILPpLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89

                           90
                   ....*....|....*.
gi 1160595254  106 N-HILSNCELVKKFLD 120
Cdd:smart00312  90 HpELINHSEVVLEFLE 105

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 260 LELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGD-TCRLLDL-------------ENSLLGLPsfyrSYFS--Q 323
Cdd:COG0515   104 LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDgRVKLIDFgiaralggatltqTGTVVGTP----GYMApeQ 179

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1160595254 324 FRKINTLESVDVHCFGHLLYEMTYGRPPdsvpvdsFPPAPSMAVVA 369
Cdd:COG0515   180 ARGEPVDPRSDVYSLGVTLYELLTGRPP-------FDGDSPAELLR 218

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  33 HTEY-IIRVQRGISVENS----WQIVRRYSDFDLLNNSL--QIAGLSLP-LPPKKLI-----GNMDREFIAERQKGLQNY 99
Cdd:COG5391   151 HTSYeIITVTNLPSFQLResrpLVVRRRYSDFESLHSILikLLPLCAIPpLPSKKSNseyygDRFSDEFIEERRQSLQNF 230

                          90       100
                  ....*....|....*....|
gi 1160595254 100 LNVITTNHILSNCELVKKFL 119
Cdd:COG5391   231 LRRVSTHPLLSNYKNSKSWE 250

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 1160595254  13 LLDDTVPLTAAIEASQSLQSHTEYIIRVQRGISVENSWQIVRRYSDFDLLNNSLQIAGLSLPLPPKKLIGNMDREFIAER 92
Cdd:cd06871     1 LLDDTVPLTCVIEASQNIQSHTEYIIRVQRGPSPENSWQVIRRYNDFDLLNASLQISGISLPLPPKKLIGNMDREFIAER 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1160595254  93 QKGLQNYLNVITTNHILSNCELVKKFLDPNNYSANYTEIA 132
Cdd:cd06871    81 QQGLQNYLNVILMNPILASCLPVKKFLDPNNYSANFTEIA 120

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 1160595254  34 TEYIIRVQRgiSVENSWQIVRRYSDFDLLNNSL--QIAGLSLPLPPKKLIG-NMDREFIAERQKGLQNYLNVITTNHILS 110
Cdd:cd07276    21 TVYKIRVEN--KVGDSWFVFRRYTDFVRLNDKLkqMFPGFRLSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIMAHKDIA 98

                  ....*....
gi 1160595254 111 NCELVKKFL 119
Cdd:cd07276    99 KCKLVREFF 107

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  33 HTEYIIRVQRGISvenswQIVRRYSDFDLLNNSLQ---IAGLSLPLPPKKLIGNMDREFIAERQKGLQNYLNVITTNHIL 109
Cdd:cd06866    18 HVEYEVSSKRFKS-----TVYRRYSDFVWLHEYLLkryPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVARHPVL 92

                          90
                  ....*....|
gi 1160595254 110 SNCELVKKFL 119
Cdd:cd06866    93 SEDELVRTFL 102

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 1160595254  19 PLTAAIEASQSLQSHTEYIIRVQRGisvENSWQIVRRYSDFDLLNNSLqIAGLSLP---LPPKKLIGNMDREFIAERQKG 95
Cdd:cd06875     3 ETKIRIPSAETVEGYTVYIIEVKVG---SVEWTVKHRYSDFAELHDKL-VAEHKVDkdlLPPKKLIGNKSPSFVEKRRKE 78

                  ....*.
gi 1160595254  96 LQNYLN 101
Cdd:cd06875    79 LEIYLQ 84

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 1160595254  36 YIIRVQR--GISVENSWQIVRRYSDFDLLNNSL--QIAGLS-LPLPPKKLIGNMDREFIAERQKGLQNYLNVITTNHILS 110
Cdd:cd06873    25 YAISVTRiyPNGQEESWHVYRRYSDFHDLHMRLkeKFPNLSkLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLD 104

                          90
                  ....*....|....*
gi 1160595254 111 NC----ELVKKFLDP 121
Cdd:cd06873   105 ANpglqEIVLDFLEP 119

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1160595254  49 SWQIVRRYSDFDLLNNSL--QIAGLSLPLPPKKLIG-NMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFL 119
Cdd:cd06870    33 SWFVFRRYAEFDKLYESLkkQFPASNLKIPGKRLFGnNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

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 1160595254  38 IRVQRGISVENSWQIVRRYSDFDLLNNSLQI-----AGLSLP-LPPKKLI----GNMDREFIAERQKGLQNYLNVITTNH 107
Cdd:cd07280    27 ITIETKDLIGSSIVAYKRYSEFVQLREALLDefprhKRNEIPqLPPKVPWydsrVNLNKAWLEKRRRGLQYFLNCVLLNP 106

                          90
                  ....*....|....
gi 1160595254 108 ILSNCELVKKFLDP 121
Cdd:cd07280   107 VFGGSPVVKEFLLP 120

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 1160595254  54 RRYSDFDLLNNSLQ-IAGLSL--PLPPKKLIGNM-DREFIAERQKGLQNYLN-VITTNHILSNCEL 114
Cdd:cd06898    41 RRYSEFVWLRNRLQkNALLIQlpSLPPKNLFGRFnNEGFIEERQQGLQDFLEkVLQTPLLLSDSRL 106

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  25 EASQSLQSHTEYIIRVQrgiSVENSWQIVRRYSDFDLLNNSLQ-IAGLSLP--LPPKKLIGNM--DREFIAERQKGLQNY 99
Cdd:cd06897     7 TTSVSPKPYTVYNIQVR---LPLRSYTVSRRYSEFVALHKQLEsEVGIEPPypLPPKSWFLSTssNPKLVEERRVGLEAF 83

                          90       100
                  ....*....|....*....|...
gi 1160595254 100 LNVI--TTNHILSNCELVKKFLD 120
Cdd:cd06897    84 LRALlnDEDSRWRNSPAVKEFLN 106

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  33 HTEYIIRvqrgisvenswqivRRYSDFDLLNNSLQIAGLSL---PLPPKK-LIGNMDR---EFIAERQKGLQNYLNVITT 105
Cdd:cd06860    34 SSEYSVR--------------RRYQDFLWLRQKLEESHPTHiipPLPEKHsVKGLLDRfspEFVATRMRALHKFLNRIVE 99

                          90
                  ....*....|....
gi 1160595254 106 NHILSNCELVKKFL 119
Cdd:cd06860   100 HPVLSFNEHLKVFL 113

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 1160595254  32 SHTEYIIRVQRGISVE--NSWQIVRRYSDFDLLNNSLQI--AGLSLPLPP-KKLIGNMDREFIAERQKGLQNYLNVITTN 106
Cdd:cd06861    17 AHTVYTVRTRTTSPNFevSSFSVLRRYRDFRWLYRQLQNnhPGVIVPPPPeKQSVGRFDDNFVEQRRAALEKMLRKIANH 96

                          90
                  ....*....|...
gi 1160595254 107 HILSNCELVKKFL 119
Cdd:cd06861    97 PVLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1160595254  54 RRYSDFDLLNNSLQI---AGLSLPLPPKKL--------IGNMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFL 119
Cdd:cd06864    50 RRYSEFELLRNYLVVtypYVIVPPLPEKRAmfmwqklsSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1160595254  51 QIVRRYSDFDLLNNSL--QIAGLSLP-LPPKKLIGNMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFL 119
Cdd:cd07286    33 QVHRRYKHFDWLYARLaeKFPVISVPhIPEKQATGRFEEDFISKRRKGLIWWMDHMCSHPVLARCDAFQHFL 104

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 160 RKKYFLMKIknqpkerlvlswadLGPDKYLSDKDFQC-LIK---LLPSCLHPYIYRVtFATANESSALLIRMFNEKGtlK 235
Cdd:cd05592    19 TNQYFAIKA--------------LKKDVVLEDDDVECtMIErrvLALASQHPFLTHL-FCTFQTESHLFFVMEYLNG--G 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 236 DLIYKAKPKDPFlkkycnpkkiqglELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGD---------TCRL-LD 305
Cdd:cd05592    82 DLMFHIQQSGRF-------------DEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREghikiadfgMCKEnIY 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1160595254 306 LEN---SLLGLPSFYRSYFSQFRKINtlESVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05592   149 GENkasTFCGTPDYIAPEILKGQKYN--QSVDWWSFGVLLYEMLIGQSP 195

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1160595254  50 WQIVRRYSDFDLLNNSLQ-----IAGLSLPLPPKKLIGNMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFLDP 121
Cdd:cd06878    50 WVVTRKLSEFHDLHRKLKecsswLKKVELPSLSKKWFKSIDKKFLDKSKNQLQKYLQFILEDETLCQSEALYSFLSP 126

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 198 IKLLPSCLHPYI--YRVTFATANEssaLLIRM-FNEKGTLKDLiykakpkdpfLKKYCNPkkiqgLELQQIKTYGRQILE 274
Cdd:cd05122    48 IAILKKCKHPNIvkYYGSYLKKDE---LWIVMeFCSGGSLKDL----------LKNTNKT-----LTEQQIAYVCKEVLK 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 275 VLKFLHDKGFPYGHLHASNVML--DGDTcRLLD-----------LENSLLGLPsfyrSYFS--QFRKINTLESVDVHCFG 339
Cdd:cd05122   110 GLEYLHSHGIIHRDIKAANILLtsDGEV-KLIDfglsaqlsdgkTRNTFVGTP----YWMApeVIQGKPYGFKADIWSLG 184

                         170
                  ....*....|..
gi 1160595254 340 HLLYEMTYGRPP 351
Cdd:cd05122   185 ITAIEMAEGKPP 196

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 260 LELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGD-TCRLLDL----EN--------SLLGLPSFYRSYFSQFRK 326
Cdd:cd05620    93 FDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDgHIKIADFgmckENvfgdnrasTFCGTPDYIAPEILQGLK 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 327 INTleSVDVHCFGHLLYEMTYGRPP----------DSVPVDS--FPPAPSMAVVAVLESTLSCEACKNgMPTISRLLQMP 394
Cdd:cd05620   173 YTF--SVDWWSFGVLLYEMLIGQSPfhgddedelfESIRVDTphYPRWITKESKDILEKLFERDPTRR-LGVVGNIRGHP 249

                         170       180
                  ....*....|....*....|..
gi 1160595254 395 LFSDVLLTTSEKPQFKIPTKLK 416
Cdd:cd05620   250 FFKTINWTALEKRELDPPFKPK 271

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 143 EPKWEVVEPLKDigwrirkKYFLMKIKNQPKERLVLSWADLGPDKYLSD-KDFQCLIKLLPSCLHPYIYRVTFATANESS 221
Cdd:cd06643     4 EDFWEIVGELGD-------GAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENN 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 222 ALLIRMFNEKGTLKDLIYKAKpkdpflkkycnpkkiQGLELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVM--LDGD 299
Cdd:cd06643    77 LWILIEFCAGGAVDAVMLELE---------------RPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILftLDGD 141

                         170       180
                  ....*....|....*....|....*.
gi 1160595254 300 -----------TCRLLDLENSLLGLP 314
Cdd:cd06643   142 ikladfgvsakNTRTLQRRDSFIGTP 167

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  20 LTAAIEASQSlQSHTEYIIRVQrgiSVEN-SWQIVRRYSDFDLLNNSLQ-IAGLSLPLPPKKLIG-NMDREFIAERQKGL 96
Cdd:cd06872     6 LGAEIVKSGS-KSFAVYSVAVT---DNENeTWVVKRRFRNFETLHRRLKeVPKYNLELPPKRFLSsSLDGAFIEERCKLL 81

                          90       100
                  ....*....|....*....|....*.
gi 1160595254  97 QNYLNVITTNHILSNCELVKKFLDPN 122
Cdd:cd06872    82 DKYLKDLLVIEKVAESHEVWSFLSAR 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; 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 have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) 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. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  25 EASQSLQSHTEYII-------RVQRGISVENSWqivRRYSDF-----DL--LNNSLQIAGLSLPLPPKKLIGNMDREFIA 90
Cdd:cd06881     9 DTRRHKKGYTEYKItskvfsrSVPEDVSEVVVW---KRYSDFkklhrELsrLHKQLYLSGSFPPFPKGKYFGRFDAAVIE 85

                          90       100       110
                  ....*....|....*....|....*....|
gi 1160595254  91 ERQKGLQNYLNVITTNHILSNCELVKKFLD 120
Cdd:cd06881    86 ERRQAILELLDFVGNHPALYQSSAFQQFFE 115

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; 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. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254  27 SQSLQSHTEY-IIRVQRGISVENSWQIVRRYSDFDLLNNSLqIAGLS-----LPLPPKKLIGNMDREFIAERQKGLQNYL 100
Cdd:cd07300    12 EQTISKHVVYqIIVIQTGSFDCNKVVIERRYSDFLKLHQEL-LSDFSeeledVVFPKKKLTGNFSEEIIAERRVALRDYL 90

                  ...
gi 1160595254 101 NVI 103
Cdd:cd07300    91 TLL 93

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 268 YGRQILEVLKFLHDKGFPYGHLHASNVMLDGDT-CRLLD------------LENSLLGLPSF-------YRSYFSqfrki 327
Cdd:cd05570   101 YAAEICLALQFLHERGIIYRDLKLDNVLLDAEGhIKIADfgmckegiwggnTTSTFCGTPDYiapeilrEQDYGF----- 175

                          90       100
                  ....*....|....*....|....
gi 1160595254 328 ntleSVDVHCFGHLLYEMTYGRPP 351
Cdd:cd05570   176 ----SVDWWALGVLLYEMLAGQSP 195

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 192 KDFQCLIKLLPSCLHPYIyrVTFATA----NESSALLIRMFNEKGTLKDLIykakpkdpflkkycnpKKIQGLELQQIKT 267
Cdd:cd13983    45 QRFKQEIEILKSLKHPNI--IKFYDSweskSKKEVIFITELMTSGTLKQYL----------------KRFKRLKLKVIKS 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595254 268 YGRQILEVLKFLHDKGFPYGH--LHASNVMLDGDT--CRLLDL----------ENSLLGLPSF-----YRSYFSqfrkin 328
Cdd:cd13983   107 WCRQILEGLNYLHTRDPPIIHrdLKCDNIFINGNTgeVKIGDLglatllrqsfAKSVIGTPEFmapemYEEHYD------ 180