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 1063704812  47 YCVTIPSWTLLSKSKNSDPIV------------------------FYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLK 102
Cdd:cd06879     1 YCVFIPSWVVLPKSKESDGKAinpkvgnmsvvyseyqplnnavdkFYRVQVGVQSPEGITTMRGVLRRFNDFLKLHTDLK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063704812 103 RAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLELE 160
Cdd:cd06879    81 KLFPKKKLPAAPPKGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFLELE 138

The phosphoinositide binding Phox Homology domain of uncharacterized 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 fungal proteins containing a 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  47 YCVTIPSWTLLSKSKNSDPIV------------------------FYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLK 102
Cdd:cd06879     1 YCVFIPSWVVLPKSKESDGKAinpkvgnmsvvyseyqplnnavdkFYRVQVGVQSPEGITTMRGVLRRFNDFLKLHTDLK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063704812 103 RAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLELE 160
Cdd:cd06879    81 KLFPKKKLPAAPPKGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFLELE 138

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1063704812  87 ILRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLE 158
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 381 LNRILLTMNERLLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEVELETTKQRNKEnlEQALMTERQSVTKMQwdmEELR 460
Cdd:pfam05483 361 LEELLRTEQQRLEKNEDQLKIITMELQKKSSELEEMTKFKNNKEVELEELKKILAE--DEKLLDEKKQFEKIA---EELK 435

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 461 QKTFEMELKLKSKEDGSSDSKTSGNSTISESHELLQEMDATKQQLEDLSRRYVELEAKSkadiKVLVREVKSLRRSHMEM 540
Cdd:pfam05483 436 GKEQELIFLLQAREKEIHDLEIQLTAIKTSEEHYLKEVEDLKTELEKEKLKNIELTAHC----DKLLLENKELTQEASDM 511

                  ....*.
gi 1063704812 541 EKELTR 546
Cdd:pfam05483 512 TLELKK 517

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 390 ERLLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEVELETTKQR--NKENLEQALMTERQSVTKMQWDMEELRQKTFEME 467
Cdd:PRK03918  165 KNLGEVIKEIKRRIERLEKFIKRTENIEELIKEKEKELEEVLREinEISSELPELREELEKLEKEVKELEELKEEIEELE 244

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 468 LKLKSKEdgssDSKTSGNSTISESHELLQEMDATKQQLEDLSRRYVELEAKSKADIKvLVREVKSLRRSHMEMEKELTRS 547
Cdd:PRK03918  245 KELESLE----GSKRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKAEEYIK-LSEFYEEYLDELREIEKRLSRL 319

                         170
                  ....*....|....*..
gi 1063704812 548 LTEKSDTEVNLKLVNKK 564
Cdd:PRK03918  320 EEEINGIEERIKELEEK 336

The phosphoinositide binding Phox Homology domain of uncharacterized 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 fungal proteins containing a 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  47 YCVTIPSWTLLSKSKNSDPIV------------------------FYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLK 102
Cdd:cd06879     1 YCVFIPSWVVLPKSKESDGKAinpkvgnmsvvyseyqplnnavdkFYRVQVGVQSPEGITTMRGVLRRFNDFLKLHTDLK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063704812 103 RAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLELE 160
Cdd:cd06879    81 KLFPKKKLPAAPPKGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFLELE 138

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 1063704812  49 VTIPSWTllSKSKNSDPIVFYRVQVSVQSPEGVStmrgILRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLE 128
Cdd:cd06093     2 VSIPDYE--KVKDGGKKYVVYIIEVTTQGGEEWT----VYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIE 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1063704812 129 ERRCSLEDWMTKLLSDIELARSVVVASFLEL 159
Cdd:cd06093    76 ERRKQLEQYLQSLLNHPELRNSEELKEFLEL 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 1063704812  49 VTIPSWTLLSKSKNSDPIVFYRVQVSVQSPEGVSTMrgILRRFNDFVKLLADLKRAFP---RKSFPSAPPKG---FLRVK 122
Cdd:cd07280     5 VNVGDYTIVGGDTGGGAYVVWKITIETKDLIGSSIV--AYKRYSEFVQLREALLDEFPrhkRNEIPQLPPKVpwyDSRVN 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1063704812 123 -SRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLE 158
Cdd:cd07280    83 lNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFLL 119

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  49 VTIPSwTLLSKSKNSDPIVFYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLKRAFPRKS---FPSAPPKGFLRVKsRD 125
Cdd:cd06876    22 VSIQS-YISDVEEEGKEFVVYLIEVQRLNNDDQSSGWVVARRYSEFLELHKYLKKRYPGVLkldFPQKRKISLKYSK-TL 99

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1063704812 126 MLEERRCSLEDWMTKLLSDIELARSVVVASFL 157
Cdd:cd06876   100 LVEERRKALEKYLQELLKIPEVCEDEEFRKFL 131

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063704812  90 RFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVkSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFL 157
Cdd:cd06885    34 RYSQLHGLNEQLKKEFGNRKLPPFPPKKLLPL-TPAQLEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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 1063704812  65 PIVFYRV----------QVSVQSPEGVSTMrgILRRFNDFVKLLADLKRAFPrKSFPSAPPKGFLRVK-SRDMLEERRCS 133
Cdd:cd07276     7 PILGYEVmeerarftvyKIRVENKVGDSWF--VFRRYTDFVRLNDKLKQMFP-GFRLSLPPKRWFKDNfDPDFLEERQLG 83

                          90       100
                  ....*....|....*....|....*..
gi 1063704812 134 LEDWMTKLLSDIELARSVVVASFLELE 160
Cdd:cd07276    84 LQAFVNNIMAHKDIAKCKLVREFFCLD 110

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 1063704812  69 YRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELA 148
Cdd:cd06873    25 YAISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLD 104

                          90
                  ....*....|....
gi 1063704812 149 RS----VVVASFLE 158
Cdd:cd06873   105 ANpglqEIVLDFLE 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  67 VFYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLKRAFPRKSFPSAPPK-----GFLRVK-------SRDMLEERRCSL 134
Cdd:cd07281    19 VVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEKHSQNGFIVPPPPeksliGMTKVKvgkedssSAEFLERRRAAL 98

                          90       100
                  ....*....|....*....|....*.
gi 1063704812 135 EDWMTKLLSDIELARSVVVASFLELE 160
Cdd:cd07281    99 ERYLQRIVSHPSLLQDPDVREFLEKE 124

The phosphoinositide binding Phox Homology domain of fungal Grd19; 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. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  81 VSTMRgilRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMtKLLSDIELAR--SVVVASFLE 158
Cdd:cd07295    37 VSSVR---RRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVIEERRQGLETFL-QSVAGHPLLQtgSKVLAAFLQ 112

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063704812  87 ILRRFNDFVKLLADLKRAFPRKSFPSAPPKgflrvksrDML--EERRCSLEDWMTKLLSDIELARSVVVASFL 157
Cdd:cd06869    52 VARRYSDFKKLHHDLKKEFPGKKLPKLPHK--------DKLprEKLRLSLRQYLRSLLKDPEVAHSSILQEFL 116

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 402 LIARLNQE-------TAVKEYLN-RKVDDLEVELETTKQRNKENleQALMTERQSVTKmqwDMEELRQKTFEMELKLKSK 473
Cdd:COG4717    47 LLERLEKEadelfkpQGRKPELNlKELKELEEELKEAEEKEEEY--AELQEELEELEE---ELEELEAELEELREELEKL 121

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063704812 474 EDgssdsktsgnstISESHELLQEMDATKQQLEDLSRRYVELEAKsKADIKVLVREVKSLRRSHMEMEKELTRSLTEKS 552
Cdd:COG4717   122 EK------------LLQLLPLYQELEALEAELAELPERLEELEER-LEELRELEEELEELEAELAELQEELEELLEQLS 187

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 1063704812  70 RVQVSVqSPEGVSTmrgILRRFNDFVKLLADLKRAfpRKSFPsAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELAR 149
Cdd:cd06871    27 RVQRGP-SPENSWQ---VIRRYNDFDLLNASLQIS--GISLP-LPPKKLIGNMDREFIAERQQGLQNYLNVILMNPILAS 99

                  ....*....
gi 1063704812 150 SVVVASFLE 158
Cdd:cd06871   100 CLPVKKFLD 108

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  49 VTIPSWTLlsKSKNSDPIVFYRVQVSVQSPEGvstmrGILRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLE 128
Cdd:cd07277     3 VWIPSVFL--RGKGSDAHHVYQVYIRIRDDEW-----NVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVE 75

                          90
                  ....*....|....
gi 1063704812 129 ERRCSLEDWMTKLL 142
Cdd:cd07277    76 ERRKRLQVYLRRVV 89

Afadin- and alpha -actinin-Binding; This family is found in mammals where it is localized at cell-cell adherens junctions, and in Sch. pombe and other fungi where it anchors spindle-pole bodies to spindle microtubules. It is a coiled-coil structure, and in pombe, it is required for anchoring the minus end of spindle microtubules to the centrosome equivalent, the spindle-pole body. The name ADIP derives from the family being composed of Afadin- and alpha -Actinin-Binding Proteins localized at Cell-Cell Adherens Junctions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 387 TMNERLLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEvELETTKQRNKENLEQALMTERQSVTKMQWD--------MEE 458
Cdd:pfam11559  56 SLNETIRTLEAEIERLQSKIERLKTQLEDLERELALLQ-AKERQLEKKLKTLEQKLKNEKEELQRLKNAlqqiktqfAHE 134

                          90
                  ....*....|....*
gi 1063704812 459 LRQKTFEMElKLKSK 473
Cdd:pfam11559 135 VKKRDREIE-KLKER 148

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  63 SDPIVFYRVQVSVQSPEGVSTMRGILRRFNDFVKLLADLKRAFPRKSFPSAPPKGFLR---VKSRDMLEERRCSLEDWMT 139
Cdd:cd06865    20 GPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVEsqvMQSAEFIEQRRVALEKYLN 99

                          90       100
                  ....*....|....*....|.
gi 1063704812 140 KLLSDIELARSVVVASFLELE 160
Cdd:cd06865   100 RLAAHPVIGLSDELRVFLTLQ 120

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 390 ERLLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEVELETTKQR--NKENLEQALMTERQSVTKMQWDMEELRQKTFEME 467
Cdd:PRK03918  165 KNLGEVIKEIKRRIERLEKFIKRTENIEELIKEKEKELEEVLREinEISSELPELREELEKLEKEVKELEELKEEIEELE 244

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 468 LKLKSKEdgssDSKTSGNSTISESHELLQEMDATKQQLEDLSRRYVELEAKSKADIKvLVREVKSLRRSHMEMEKELTRS 547
Cdd:PRK03918  245 KELESLE----GSKRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKAEEYIK-LSEFYEEYLDELREIEKRLSRL 319

                         170
                  ....*....|....*..
gi 1063704812 548 LTEKSDTEVNLKLVNKK 564
Cdd:PRK03918  320 EEEINGIEERIKELEEK 336

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; 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 SNX20, SNX21, and similar proteins. 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. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  67 VFYRVQVsVQSPEGVSTMRGILRRFNDFVKLLADLKRAFP----RKSFPSappKGFLRVKSRDMLEERRCSLEDWMTKLL 142
Cdd:cd07279    19 VVYQLAV-VQTGDPDTQPAFIERRYSDFLKLYKALRKQHPqlmaKVSFPR---KVLMGNFSSELIAERSRAFEQFLGHIL 94

                          90
                  ....*....|....*...
gi 1063704812 143 SDIELARSVVVASFLELE 160
Cdd:cd07279    95 SIPNLRDSKAFLDFLQGP 112

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812 379 SKLNRILLTMNERLLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEVELETTKQRNKEnLEQALMTERQSVTKMQWDMEE 458
Cdd:COG4372    41 DKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQ-AQEELESLQEEAEELQEELEE 119

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063704812 459 LRQKTFEMELKLKSKEDGSSDSKTSGNSTISESHELLQEMDATKQQLEDLSRRYVELE-AKSKADIKVLVREVK 531
Cdd:COG4372   120 LQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSeAEAEQALDELLKEAN 193

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  59 KSKNSDPIVFYRVQ-----VSVQSPEGVSTMRGIL------RRFNDFVKLL------ADLKRAFPRKsfpsAPPKGFLRV 121
Cdd:cd06893    14 KGTGTHPYTLYTVQyetilDVQSEQNPNAASEQPLathtvnRRFREFLTLQtrleenPKFRKIMNVK----GPPKRLFDL 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1063704812 122 KSRDM----LEERRCSLEDWMTKLLSDIELARSVVVASFLEL 159
Cdd:cd06893    90 PFGNMdkdkIEARRGLLETFLRQLCSIPEISNSEEVQEFLAY 131

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 1063704812  89 RRFNDFVKLLADLKRAFPRKSFPSAPPKGFLRVKSRDMLEERRCSLEDWMTKLLSDIELARSVVVASFLELEATARSA 166
Cdd:cd07286    36 RRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKGLIWWMDHMCSHPVLARCDAFQHFLTCPSTDEKA 113

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  392 LLNSKTDMEDLIARLNQETAVKEYLNRKVDDLEVELETTKQrNKENLEQALMTERQSVTKMQWDMEELRQKTFEMELKLK 471
Cdd:TIGR02168  672 ILERRREIEELEEKIEELEEKIAELEKALAELRKELEELEE-ELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIA 750

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063704812  472 SKEDgssdsktsgnstisESHELLQEMDATKQQLEDLSRRYVELEAKS---KADIKVLVREVKSLRRSHMEMEKELTR 546
Cdd:TIGR02168  751 QLSK--------------ELTELEAEIEELEERLEEAEEELAEAEAEIeelEAQIEQLKEELKALREALDELRAELTL 814

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  400 EDLIARLNQETAVKEYLNRKVDDL----EVELETTKQRNKENLEQALMTERQSVTKMQwDMEELRQKTFEMELKLKSKED 475
Cdd:TIGR02169  261 SELEKRLEEIEQLLEELNKKIKDLgeeeQLRVKEKIGELEAEIASLERSIAEKERELE-DAEERLAKLEAEIDKLLAEIE 339

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  476 GSSDSKTSGN----STISESHELLQEMDATKQQLEDLSRRYVELEAKSKAdikvLVREVKSLRRSHMEMEKELTRSLTEK 551
Cdd:TIGR02169  340 ELEREIEEERkrrdKLTEEYAELKEELEDLRAELEEVDKEFAETRDELKD----YREKLEKLKREINELKRELDRLQEEL 415

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063704812  378 HSKLNRILLTMNERllnsKTDMEDLIARLNQetavkeyLNRKVDDLEVELETTKQRNKENLEQALMTERQSvtkmqwdmE 457
Cdd:TIGR02168  266 EEKLEELRLEVSEL----EEEIEELQKELYA-------LANEISRLEQQKQILRERLANLERQLEELEAQL--------E 326