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 1063730437 143 KITVSNPQKEQEATNSmIPGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQ 222
Cdd:cd06865     1 KITVSDPKKEQEPSRV-PLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063730437 223 VMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd06865    80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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 1063730437 143 KITVSNPQKEQEATNSmIPGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQ 222
Cdd:cd06865     1 KITVSDPKKEQEPSRV-PLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063730437 223 VMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd06865    80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 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 1063730437  161 PGGSTYITYQITTRTNLSdyggsEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQVMQKQEFVEQRRVALEKY 240
Cdd:smart00312   9 DGKHYYYVIEIETKTGLE-----EWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|..
gi 1063730437  241 LRRLVAHPVIRN-SDELKVFLQ 261
Cdd:smart00312  84 LQSLLNHPELINhSEVVLEFLE 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 142 IKITVSNPQKEQEATNSmipgGSTYITYQITTRTNLSDYGGSEF---SVRRRFRDIVTLADRLAESYRGFCIPPRPDKSI 218
Cdd:COG5391   131 ISSTVSNPQSLTLLVDS----RDKHTSYEIITVTNLPSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKKS 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 219 VESQVMQK--QEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFlqaqgklpLATSTDVASRMLDGAVKLPKQLfgegggA 296
Cdd:COG5391   207 NSEYYGDRfsDEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSW--------ESHSTLLSSFIENRKSVPTPLS------L 272

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 297 SSVEVVQPGRGGRDFLRMF-KELRQSVSNDWGGSKPPVVE---EDKEFLEKKEKMYDLEQQIINASQQAESLVKAQQD-- 370
Cdd:COG5391   273 DLTSTTQELDMERKELNEStSKAIHNILSIFSLFEKILIQlesEEESLTRLLESLNNLLLLVLNFSGVFAKRLEQNQNsi 352

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 371 ----MGETMGELGLAFIKLTKFENEEAVFNS-QRARANDMKnlatsavkasrfYRELNSQTVkhlDTLHDYLgLMMAVQG 445
Cdd:COG5391   353 lnegVVQAETLRSSLKELLTQLQDEIKSRESlILTDSNLEK------------LTDQNLEDV---EELSRSL-RKNSSQR 416

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 446 AFADRSSALLTVQTLLSELSSLearaeklevasskvFGGDKSRIKKIEELKETIKVTEDSKNVAIREYEQIKENNWSEVE 525
Cdd:COG5391   417 AVVSQQPEGLTSFSKLSYKLRD--------------FVQEKSRSKSIESLQQDKEKLEEQLAIAEKDAQEINEELKNELK 482

                         410       420       430
                  ....*....|....*....|....*....|....*...
gi 1063730437 526 RLDRERRADFLNMMKGFVANQVGYAEKIANVWTKVAEE 563
Cdd:COG5391   483 FFFSVRNSDLEKILKSVADSHIEWAEENLEIWKSVKEQ 520

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 1063730437  333 VVEEDKEFLEKKEKMYDLEQQIINASQQAESLVKAQQDMGETMGELGLAFIKLTKFENE-EAVFNSQRARANDMKNLATS 411
Cdd:TIGR02168  283 IEELQKELYALANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAElEEKLEELKEELESLEAELEE 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437  412 AVKAsrfYRELNSQtVKHLDTLHDYLglmmavQGAFADRSSALL----TVQTLLSELSSLEARAEKL----EVASSKVFG 483
Cdd:TIGR02168  363 LEAE---LEELESR-LEELEEQLETL------RSKVAQLELQIAslnnEIERLEARLERLEDRRERLqqeiEELLKKLEE 432

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437  484 GDKSRIK-----KIEELKETIKVTEDSKNVAIREYEQIKENNWSEVERLDRERRADF-LNMMKGFVANQVGYAEKIANVW 557
Cdd:TIGR02168  433 AELKELQaeleeLEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQArLDSLERLQENLEGFSEGVKALL 512

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 1063730437 143 KITVSNPQKEQEATNSmIPGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQ 222
Cdd:cd06865     1 KITVSDPKKEQEPSRV-PLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063730437 223 VMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd06865    80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor 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. SNX1 and SNX2 are components 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 142 IKITVSNPQKEQEATNSmipggstYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVES 221
Cdd:cd06859     1 FEISVTDPVKVGDGMSA-------YVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGR 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1063730437 222 qVMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd06859    74 -FKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 142 IKITVSNPQKEQEATNSmipggstYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYR--GFCIPPRPDKSI- 218
Cdd:cd07282     1 IEIGVSDPEKVGDGMNA-------YMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIv 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063730437 219 ------VESQVMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQA 262
Cdd:cd07282    74 gmtkvkVGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 123

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX 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. 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 1063730437 142 IKITVSNPQKEQEAtnsmipGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVES 221
Cdd:cd06863     1 LECLVSDPQKELDG------SSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEY 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063730437 222 QVMQK--QEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFL 260
Cdd:cd06863    75 ITGDRfsPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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 1063730437 142 IKITVSNPQKEQEATNSmipggstYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAE--SYRGFCIPPRPDKSI- 218
Cdd:cd07281     1 LKVSITDPEKIGDGMNA-------YVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhSQNGFIVPPPPEKSLi 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1063730437 219 ------VESQVMQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd07281    74 gmtkvkVGKEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFLEKE 124

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 144 ITVSNPQKEqeatnsmIPGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQV 223
Cdd:cd07283     3 VTVDDPKKH-------VCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVV 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1063730437 224 MQ-KQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd07283    76 DRfSEEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 181 GGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQvmqKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFL 260
Cdd:pfam00787   5 SLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY---NEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

                  .
gi 1063730437 261 Q 261
Cdd:pfam00787  82 E 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 142 IKITVSNPQKEQEATNSmipgGSTYITYQITTRTNLSDYGGSEF---SVRRRFRDIVTLADRLAESYRGFCIPPRPDKSI 218
Cdd:COG5391   131 ISSTVSNPQSLTLLVDS----RDKHTSYEIITVTNLPSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKKS 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 219 VESQVMQK--QEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFlqaqgklpLATSTDVASRMLDGAVKLPKQLfgegggA 296
Cdd:COG5391   207 NSEYYGDRfsDEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSW--------ESHSTLLSSFIENRKSVPTPLS------L 272

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 297 SSVEVVQPGRGGRDFLRMF-KELRQSVSNDWGGSKPPVVE---EDKEFLEKKEKMYDLEQQIINASQQAESLVKAQQD-- 370
Cdd:COG5391   273 DLTSTTQELDMERKELNEStSKAIHNILSIFSLFEKILIQlesEEESLTRLLESLNNLLLLVLNFSGVFAKRLEQNQNsi 352

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 371 ----MGETMGELGLAFIKLTKFENEEAVFNS-QRARANDMKnlatsavkasrfYRELNSQTVkhlDTLHDYLgLMMAVQG 445
Cdd:COG5391   353 lnegVVQAETLRSSLKELLTQLQDEIKSRESlILTDSNLEK------------LTDQNLEDV---EELSRSL-RKNSSQR 416

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 446 AFADRSSALLTVQTLLSELSSLearaeklevasskvFGGDKSRIKKIEELKETIKVTEDSKNVAIREYEQIKENNWSEVE 525
Cdd:COG5391   417 AVVSQQPEGLTSFSKLSYKLRD--------------FVQEKSRSKSIESLQQDKEKLEEQLAIAEKDAQEINEELKNELK 482

                         410       420       430
                  ....*....|....*....|....*....|....*...
gi 1063730437 526 RLDRERRADFLNMMKGFVANQVGYAEKIANVWTKVAEE 563
Cdd:COG5391   483 FFFSVRNSDLEKILKSVADSHIEWAEENLEIWKSVKEQ 520

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 142 IKITVSNPQKEqeATNSMIPGGSTYITYQITTRtnlSDYGGSEF-------SVRRRFRDIVTLADRLAESYRGFCIPPRP 214
Cdd:cd06864     1 MEITVTEAEKR--TGGSAMNLKETYTVYLIETK---IVEHESEEglskklsSLWRRYSEFELLRNYLVVTYPYVIVPPLP 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063730437 215 DKSIveSQVMQK-------QEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQ 261
Cdd:cd06864    76 EKRA--MFMWQKlssdtfdPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLT 127

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 144 ITVSNPQKEQEAtnsmipGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESqv 223
Cdd:cd06898     2 VEVRDPRTHKED------DWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGR-- 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063730437 224 MQKQEFVEQRRVALEKYLRRLVAHPVIRNSDELKVFLQAQ 263
Cdd:cd06898    74 FNNEGFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQTQ 113

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 1063730437 166 YITYQITTRTNLSdyggsefSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVESQvmqKQEFVEQRRVALEKYLRRLV 245
Cdd:cd06866    18 HVEYEVSSKRFKS-------TVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSA---DREFLEARRRGLSRFLNLVA 87

                          90
                  ....*....|....*
gi 1063730437 246 AHPVIRNSDELKVFL 260
Cdd:cd06866    88 RHPVLSEDELVRTFL 102

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 1063730437 153 QEATNSMIP---------------GGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKS 217
Cdd:cd06876    10 QENDNSLYGrtrvsiqsyisdveeEGKEFVVYLIEVQRLNNDDQSSGWVVARRYSEFLELHKYLKKRYPGVLKLDFPQKR 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063730437 218 IVESQVMQKQeFVEQRRVALEKYLRRLVAHPVIRNSDELKVFL 260
Cdd:cd06876    90 KISLKYSKTL-LVEERRKALEKYLQELLKIPEVCEDEEFRKFL 131

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 1063730437 141 YIKITVSNPQkeqeatnSMIPGGSTYITYQITTRTNLSDYGGSEFSVRRRFRDIVTLADRLAESYRGFCIPPRPDKSIVE 220
Cdd:cd07295     1 FLEIEVRNPK-------THGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTN 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063730437 221 SqvmQKQEFVEQRRVALEKYLRRLVAHPVIRN-SDELKVFLQAQG 264
Cdd:cd07295    74 R---FSDEVIEERRQGLETFLQSVAGHPLLQTgSKVLAAFLQDPK 115

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 1063730437 162 GGSTYITYQITTRTNlsDYGGSEFSVRRRFRDIVTLADRLAESYRGFC---IPPRPDKSIV-ESQVMQKQEFVEQRRVAL 237
Cdd:cd07280    18 GGGAYVVWKITIETK--DLIGSSIVAYKRYSEFVQLREALLDEFPRHKrneIPQLPPKVPWyDSRVNLNKAWLEKRRRGL 95

                          90       100
                  ....*....|....*....|...
gi 1063730437 238 EKYLRRLVAHPVIRNSDELKVFL 260
Cdd:cd07280    96 QYFLNCVLLNPVFGGSPVVKEFL 118

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 1 and 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. This subfamily consists of SNX1, SNX2, and similar proteins. SNX1 and SNX2 are components 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 332 PVVEEDKEFLEKKEKMYDLEQQIINASQQAESLVKAQQDMGETMGELGLAFIKLTKFENEEAVfnsqrARAndMKNLATS 411
Cdd:cd07623     6 KMDETDQWFEEKQQQIENLDQQLRKLHASVESLVNHRKELALNTGSFAKSAAMLSNCEEHTSL-----SRA--LSQLAEV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 412 AVKASRFYREL-NSQTVKHLDTLHDYLGLMMAVQGAFADRSSALLTVQTLLSELSSL-EARAeKLEVASskvfggdksRI 489
Cdd:cd07623    79 EEKIEQLHGEQaDTDFYILAELLKDYIGLIGAIKDVFHERVKVWQNWQNAQQTLTKKrEAKA-KLELSG---------RT 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1063730437 490 KKIEELKETIKVTEDSKNVAIREYEQIKENNWSEVERLDRERRADFLNMMKGFVANQVGYAEKIANVWTKVAEETR 565
Cdd:cd07623   149 DKLDQAQQEIKEWEAKVDRGQKEFEEISKTIKKEIERFEKNRVKDFKDIIIKYLESLLNTQQQLIKYWEAFLPEAK 224

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 1063730437 151 KEQEATNSMIPGGSTYITYQITTRT-----------NLSDYGGSEFSVRRRFRDIVTLADRLAES--YRGFCIPPRPDKS 217
Cdd:cd06893     6 KTITAKEYKGTGTHPYTLYTVQYETildvqseqnpnAASEQPLATHTVNRRFREFLTLQTRLEENpkFRKIMNVKGPPKR 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063730437 218 IVE--SQVMQKQEfVEQRRVALEKYLRRLVAHPVIRNSDELKVFL 260
Cdd:cd06893    86 LFDlpFGNMDKDK-IEARRGLLETFLRQLCSIPEISNSEEVQEFL 129

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Vps5p; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 335 EEDKEFLEKKEKMYDLEQQIINASQQAESLVKAQQDMGETMGELGLAFIKLTKFENEEAVfnsqrarANDMKNLATSAVK 414
Cdd:cd07627     1 EPDEWFIEKKQYLDSLESQLKQLYKSLELVSSQRKELASATEEFAETLEALSSLELSKSL-------SDLLAALAEVQKR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063730437 415 ASRFYRELNSQTVKHLD-TLHDYLGLMMAVQGAFADRSSALLTVQTLLSELSSLEARAEKLEVASskvfggdKSRIKKIE 493
Cdd:cd07627    74 IKESLERQALQDVLTLGvTLDEYIRSIGSVRAAFAQRQKLWQYWQSAESELSKKKAQLEKLKRQG-------KTQQEKLN 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063730437 494 ELKETIKVTEDSKNVAIREYEQIKENNWSEVERLDRERRADFLNMMKGFV 543
Cdd:cd07627   147 SLLSELEEAERRASELKKEFEEVSELIKSELERFERERVEDFRNSVEIYL 196