Atypical FERM-like domain C-lobe of Sorting nexin 17; SNX17 is a beta1-integrin-tail-binding protein that interacts with the free kindlin-binding site in endosomes to stabilize beta1 integrins, resulting in their recycling to the cell surface where they can be reused. SNX17 contains a N-terminal PX domain, a FERM-like domain, and a unique C-terminal region. SNX17 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. FERM domains are found in cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 257 YGYLRFDACVADFPEKDCPVVVSAGNSELSLQLRLPGQQLREGSFRVTRMRCWRVTSSVPLPSgstsspgRGRGEVRLEL 336
Cdd:cd13337    1 YGYIQFEPCICDYPKPGTRVLVSIGNRELNFRLKDEEGKVKEGSFRVTRMRCWRITASHIEED-------SKKDEKKLEL 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 388596705 337 AFEYLMSKDRLQWVTITSPQAIMMSICLQSMVDELMVKKS 376
Cdd:cd13337   74 SFEYLMSKDKLQWITIRSDQAILMSLCLQSMVDELLRKKN 113

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 17 (SNX17); SNX17 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. It localizes to early endosomes, and plays an important role in mediating endocytic internalization, recycling, and/or protection from lysosomal degradation of NPxY-motif containing cell surface proteins including amyloid precursor protein (APP), P-selectin, beta1-integrin, low density lipoprotein receptor (LDLR), LDLR related protein (Lrp1), ApoER2, and FEEL1. SNX17 also affects T cell activation by regulating T cell receptor and integrin recycling. SNX17 contains a PX (Phox homology) domain and a FERM (Band 4.1, ezrin, radixin, moesin) domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 103 EEVSLEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREKEDGAFSFVRKLQEFELPYVSVTSLRS 182
Cdd:cd16121    1 EEVSLDVFLMNGQKITVNISSTDQTDDVLEAVASKLGLPEELVYYFALFLVKKDDDGNNTIVRKLQDFESPYLSLKSAGK 80

                         90
                 ....*....|...
gi 388596705 183 QEYKIVLRKSYWD 195
Cdd:cd16121   81 GSHRIVLRKSYWD 93

Atypical FERM-like domain C-lobe of Sorting nexin 17; SNX17 is a beta1-integrin-tail-binding protein that interacts with the free kindlin-binding site in endosomes to stabilize beta1 integrins, resulting in their recycling to the cell surface where they can be reused. SNX17 contains a N-terminal PX domain, a FERM-like domain, and a unique C-terminal region. SNX17 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. FERM domains are found in cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 257 YGYLRFDACVADFPEKDCPVVVSAGNSELSLQLRLPGQQLREGSFRVTRMRCWRVTSSVPLPSgstsspgRGRGEVRLEL 336
Cdd:cd13337    1 YGYIQFEPCICDYPKPGTRVLVSIGNRELNFRLKDEEGKVKEGSFRVTRMRCWRITASHIEED-------SKKDEKKLEL 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 388596705 337 AFEYLMSKDRLQWVTITSPQAIMMSICLQSMVDELMVKKS 376
Cdd:cd13337   74 SFEYLMSKDKLQWITIRSDQAILMSLCLQSMVDELLRKKN 113

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 17 (SNX17); SNX17 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. It localizes to early endosomes, and plays an important role in mediating endocytic internalization, recycling, and/or protection from lysosomal degradation of NPxY-motif containing cell surface proteins including amyloid precursor protein (APP), P-selectin, beta1-integrin, low density lipoprotein receptor (LDLR), LDLR related protein (Lrp1), ApoER2, and FEEL1. SNX17 also affects T cell activation by regulating T cell receptor and integrin recycling. SNX17 contains a PX (Phox homology) domain and a FERM (Band 4.1, ezrin, radixin, moesin) domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 103 EEVSLEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREKEDGAFSFVRKLQEFELPYVSVTSLRS 182
Cdd:cd16121    1 EEVSLDVFLMNGQKITVNISSTDQTDDVLEAVASKLGLPEELVYYFALFLVKKDDDGNNTIVRKLQDFESPYLSLKSAGK 80

                         90
                 ....*....|...
gi 388596705 183 QEYKIVLRKSYWD 195
Cdd:cd16121   81 GSHRIVLRKSYWD 93

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 388596705     7 ETESRSGDSGGSAYVAYNIHVNGV---------------LHCRLRKEYGANVLPAFPPKKLFSLTPAE----VEQRREQL 67
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGleewtvsrrysdfleLHSKLKKHFPRSILPPLPGKKLFGRLNNFseefIEKRRRGL 80

                           90       100
                   ....*....|....*....|....
gi 388596705    68 EKYMQAVRQDPLLGS-SETFNSFL 90
Cdd:smart00312  81 EKYLQSLLNHPELINhSEVVLEFL 104

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705   107 LEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLigYFSLFLVREKEDgafsfvrkLQEFELPYVSVTSLRSQ--E 184
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESE--YFGLQFEDPDED--------LRHWLDPAKTLLDQDVKseP 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 388596705   185 YKIVLRKSYWdsaYDDDVM--ENRVGLNLLYAQTVSDIERGWILVTKEQHRQLKSLQ 239
Cdd:smart00295  72 LTLYFRVKFY---PPDPNQlkEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALA 125

Atypical FERM-like domain C-lobe of Sorting nexin 17; SNX17 is a beta1-integrin-tail-binding protein that interacts with the free kindlin-binding site in endosomes to stabilize beta1 integrins, resulting in their recycling to the cell surface where they can be reused. SNX17 contains a N-terminal PX domain, a FERM-like domain, and a unique C-terminal region. SNX17 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. FERM domains are found in cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 257 YGYLRFDACVADFPEKDCPVVVSAGNSELSLQLRLPGQQLREGSFRVTRMRCWRVTSSVPLPSgstsspgRGRGEVRLEL 336
Cdd:cd13337    1 YGYIQFEPCICDYPKPGTRVLVSIGNRELNFRLKDEEGKVKEGSFRVTRMRCWRITASHIEED-------SKKDEKKLEL 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 388596705 337 AFEYLMSKDRLQWVTITSPQAIMMSICLQSMVDELMVKKS 376
Cdd:cd13337   74 SFEYLMSKDKLQWITIRSDQAILMSLCLQSMVDELLRKKN 113

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705   2 HFSIPETESRSgDSGGSAYVAYNIHVNGVLHCR------------LRKEYGANVLPAFPPKKLFSLTPAEVEQRREQLEK 69
Cdd:cd06885    1 HFSIPDTQELS-DEGGSTYVAYNIHINGVLHCSvrysqlhglneqLKKEFGNRKLPPFPPKKLLPLTPAQLEERRLQLEK 79

                         90       100
                 ....*....|....*....|....*
gi 388596705  70 YMQAVRQDPLLGSSETFNSFLRRAQ 94
Cdd:cd06885   80 YLQAVVQDPRIANSDIFNSFLLNAQ 104

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in PX-FERM family sorting nexin proteins; This family includes three endosome-associated PX (Phox homology) and FERM (Band 4.1, ezrin, radixin, moesin) domain-containing proteins called sorting nexin (SNX) 17, SNX27, and SNX31, which are modular peripheral membrane proteins acting as central scaffolds mediating protein-lipid interactions, cargo binding, and regulatory protein recruitment. They are key regulators of endosomal recycling and bind conserved NPX(Y/F) peptide sorting motifs in transmembrane cargos via an atypical FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 103 EEVSLEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREKEDGAFSFVRKLQEFELPYVSVTSLRS 182
Cdd:cd17109    1 SDVELRVALPNGQTVTVRVKTSDTTEQVLEAVAAKVGLDSTLVGYFALFLVRSHSEGKLSFVRKLAPFELPYVSYISNYT 80

                         90
                 ....*....|...
gi 388596705 183 QEYKIVLRKSYWD 195
Cdd:cd17109   81 PGTKLTLRKWYFT 93

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 31 (SNX31); SNX31 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. It is a novel sorting nexin associated with the uroplakin-degrading multivesicular bodies in terminally differentiated urothelial cells. SNX31 binds multiple beta integrin cytoplasmic domains and regulates beta1 integrin surface levels and stability. SNX31 contains a PX (Phox homology) domain and a FERM (Band 4.1, ezrin, radixin, moesin) domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705 100 VPTEEVSLEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREKEDGAFSFVRKLQEFELPYVSVTS 179
Cdd:cd16122    1 IHTLKAVLDVYLPDGRSVRIDVKTSDTAERVLEVVLDRIGLSRELRGYFSLFLVKGKGKGDFSVVKKLAPFELPYVTLES 80

                         90
                 ....*....|....*.
gi 388596705 180 LRSQEYKIVLRKSYWD 195
Cdd:cd16122   81 GEMERCKLGIRKWYMD 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 388596705   2 HFSIPETESRSGdsGGSAYVAYNIHVNG----------------VLHCRLRKEYGANVLPAFPPKKLF-SLTPAEVEQRR 64
Cdd:cd06093    1 SVSIPDYEKVKD--GGKKYVVYIIEVTTqggeewtvyrrysdfeELHEKLKKKFPGVILPPLPPKKLFgNLDPEFIEERR 78

                         90       100
                 ....*....|....*....|....*..
gi 388596705  65 EQLEKYMQAVRQDPLLGSSETFNSFLR 91
Cdd:cd06093   79 KQLEQYLQSLLNHPELRNSEELKEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 388596705   31 LHCRLRKEYGANVLPAFPPKK-LFSLTPAEVEQRREQLEKYMQAVRQDPLLGSSETFNSFL 90
Cdd:pfam00787  21 LHKKLLRKFPSVIIPPLPPKRwLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 27 (SNX27); SNX27 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. In addition to a PX (Phox homology) domain that regulates its endosomal localization, SNX27 has a unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin, moesin) domain that both function to bind short peptide sequence motifs in the cytoplasmic domains of the cargo receptors. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 388596705 104 EVSLEVLLSNGQKVLVNVLTSDQTEDVLEAVAAKLDLPDDLIGYFSLFLVREkedgaFSFVRKLQEFELPY 174
Cdd:cd01777    2 DVELKVLLPDRTTVTVSVKKNSNTDQVYQALVEKLGMDSETANYFALFEIIE-----YNFERKLQPNEFPH 67

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
                 ....*....|....*....|....*....|....*....|....
gi 388596705  31 LHCRLRKEYGAnvlPAFPPKKLFSLTPAEVEQRREQLEKYMQAV 74
Cdd:cd06880   45 LHKKLKKSIKT---PDFPPKRVRNWNPKVLEQRRQGLEAYLQGL 85

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705  31 LHCRLRKEYGANVLPAFPPKKLFsLTPAEVEQRREQLEKYMQAVRQDPLLGSSETFNSFL 90
Cdd:cd06868   59 LYKKLSEKYPGTILPPLPRKALF-VSESDIRERRAAFNDFMRFISKDEKLANCPELLEFL 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388596705   2 HFSIPETESRSGDSGGSAYVAYNIH--VNGV-----------LHCRLRKEYGANVLPAFPPKKLFSLTPAE-VEQRREQL 67
Cdd:cd06862    2 HCTVTNPKKESKFKGLKSFIAYQITptHTNVtvsrrykhfdwLYERLVEKYSCIAIPPLPEKQVTGRFEEDfIEKRRERL 81

                         90       100
                 ....*....|....*....|...
gi 388596705  68 EKYMQAVRQDPLLGSSETFNSFL 90
Cdd:cd06862   82 ELWMNRLARHPVLSQSEVFRHFL 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 388596705  30 VLHCRLRKEYGANVLPAFPPKKLFSLTPAE---VEQRREQLEKYMQAVRQDPLLGSSETFNSFL 90
Cdd:cd06876   68 ELHKYLKKRYPGVLKLDFPQKRKISLKYSKtllVEERRKALEKYLQELLKIPEVCEDEEFRKFL 131

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
                 ....*....|....*....|....*....|....*....|....*...
gi 388596705  44 LPaFPPKKLF-SLTPAEVEQRREQLEKYMQAVRQDPLLGSSETFNSFL 90
Cdd:cd06871   61 LP-LPPKKLIgNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

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
                 ....*....|....*....|....*....|....*....|....*..
gi 388596705  31 LHCRLRKEY--GANVLPafpPKKLF-SLTPAEVEQRREQLEKYMQAV 74
Cdd:cd06875   43 LHDKLVAEHkvDKDLLP---PKKLIgNKSPSFVEKRRKELEIYLQTL 86

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

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gi 388596705  34 RLRKEYGANVLPAFPPKKLFSLT----PAEVEQRREQLEKYMQAVRQDPLLGSSETFNSFLR 91
Cdd:cd06865   57 RLAEAYRGAFVPPRPDKSVVESQvmqsAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLT 118

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.

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gi 388596705  31 LHCRLRKEYGANVLPAFPPKKLFSLTPAE-VEQRREQLEKYMQAV 74
Cdd:cd07277   44 LHKKLKKKFPVVRSFDFPPKKAIGNKDAKfVEERRKRLQVYLRRV 88

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.

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gi 388596705  30 VLHCRLRKEYGANVLPAFPPKKL---FSLTPAE------VEQRREQLEKYMQAVRQDPLLGSSETFNSFL 90
Cdd:cd06864   57 LLRNYLVVTYPYVIVPPLPEKRAmfmWQKLSSDtfdpdfVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126