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 1955874124 130 KITVSNPQKEQDVSnSIVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVEGQ 209
Cdd:cd06865     1 KITVSDPKKEQEPS-RVPLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955874124 210 VMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVQ 250
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 1955874124 130 KITVSNPQKEQDVSnSIVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVEGQ 209
Cdd:cd06865     1 KITVSDPKKEQEPS-RVPLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955874124 210 VMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVQ 250
Cdd:cd06865    80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 129 IKITVSNPQKE-QDVSNSivpggNSYVTYLITTRTNIADFGGSEF---SVRRRFKDVVTLSERLAESYRGFFIPPRPDKS 204
Cdd:COG5391   131 ISSTVSNPQSLtLLVDSR-----DKHTSYEIITVTNLPSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKK 205

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 205 VVEGQVMQK--QEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVqgrlplptttdvaSRMLDGAVNLPKQLLNESAM 282
Cdd:COG5391   206 SNSEYYGDRfsDEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSWESH-------------STLLSSFIENRKSVPTPLSL 272

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 283 APQEVVQpaKGGRDLLRLFKELKQSVTNDWGSSKppvvEEDKEFLEKKEKLRDFEQQLSaTSQQAESLVKAQqdmaetyg 362
Cdd:COG5391   273 DLTSTTQ--ELDMERKELNESTSKAIHNILSIFS----LFEKILIQLESEEESLTRLLE-SLNNLLLLVLNF-------- 337

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 363 eLGLTLIKLTKFENEEA-----VFNGQRVCAADTKNiataavkasrlYRELNAQTVKHLDVLHDYLGLMLAVHGAFSE-- 435
Cdd:COG5391   338 -SGVFAKRLEQNQNSILnegvvQAETLRSSLKELLT-----------QLQDEIKSRESLILTDSNLEKLTDQNLEDVEel 405

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 436 -RSSALLTEQTLLSDLSSLNTRAEKLEAASSKVFGGDKSRIQKLEQLKETIRTTEDAKNVAMREYERIKENNRSELERFD 514
Cdd:COG5391   406 sRSLRKNSSQRAVVSQQPEGLTSFSKLSYKLRDFVQEKSRSKSIESLQQDKEKLEEQLAIAEKDAQEINEELKNELKFFF 485

                         410       420       430
                  ....*....|....*....|....*....|....*....
gi 1955874124 515 RERQADFLSMLKGFVTNQVGYAEKISDVWAKVAEETSSY 553
Cdd:COG5391   486 SVRNSDLEKILKSVADSHIEWAEENLEIWKSVKEQLDRL 524

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 167 FGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVegqVMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVF 246
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWL---GRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEF 80

                  ....
gi 1955874124 247 LQVQ 250
Cdd:pfam00787  81 LESD 84

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124  291 AKGGRDLLRLFKELKQSVTNDWGSSKPpvveEDKEFLEKKEK-LRDFEQQLSATSQQAESLVKAQQDMAETYGELGLTLI 369
Cdd:TIGR00618  192 LHGKAELLTLRSQLLTLCTPCMPDTYH----ERKQVLEKELKhLREALQQTQQSHAYLTQKREAQEEQLKKQQLLKQLRA 267

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124  370 KLTKFENEEAVFNGQR----------VCAADTKNIATAAVKASRLYRELNAQTVKHLDVLHDYLGLMlavhgafsERSSA 439
Cdd:TIGR00618  268 RIEELRAQEAVLEETQerinrarkaaPLAAHIKAVTQIEQQAQRIHTELQSKMRSRAKLLMKRAAHV--------KQQSS 339

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124  440 LLTEQTLLSDLSS---LNTRAEKLEAASSKVFGGDKSRIQKLEQLKETIRTTEDAKNVAMREYERIKENNRSELERFDRE 516
Cdd:TIGR00618  340 IEEQRRLLQTLHSqeiHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLTQKLQSLCKELDILQREQATIDTRTSAF 419

                   .
gi 1955874124  517 R 517
Cdd:TIGR00618  420 R 420

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 1955874124 130 KITVSNPQKEQDVSnSIVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVEGQ 209
Cdd:cd06865     1 KITVSDPKKEQEPS-RVPLGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955874124 210 VMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVQ 250
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 1955874124 129 IKITVSNPQKEQDvsnsivpGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVeG 208
Cdd:cd06859     1 FEISVTDPVKVGD-------GMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAV-G 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1955874124 209 QVMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd06859    73 RFKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLE 112

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 130 KITVSNPQKEQDVSNSivpggnsYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVeGQ 209
Cdd:cd06861     2 EITVGDPHKVGDLTSA-------HTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSV-GR 73

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1955874124 210 VmqKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd06861    74 F--DDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

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 1955874124 129 IKITVSNPQKEQDvsnsivpGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYR--GFFIPPRPDKSVV 206
Cdd:cd07282     1 IEIGVSDPEKVGD-------GMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIV 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1955874124 207 eGQVMQK--------QEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd07282    74 -GMTKVKvgkedsssTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 122

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 1955874124 129 IKITVSNPQKEQDvsnsivpGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAE--SYRGFFIPPRPDKSV- 205
Cdd:cd07281     1 LKVSITDPEKIGD-------GMNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhSQNGFIVPPPPEKSLi 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1955874124 206 ------VEGQVMQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd07281    74 gmtkvkVGKEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFLE 122

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 1955874124 131 ITVSNPQKEqdvsnsiVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVEGQV 210
Cdd:cd07283     3 VTVDDPKKH-------VCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVV 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1955874124 211 MQ-KQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVQ 250
Cdd:cd07283    76 DRfSEEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

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 1955874124  145 SIVPGGNSYVTYLITTRTNiadfgGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVEGQVMQKQEFVEQRRLAL 224
Cdd:smart00312   6 KIGDGKHYYYVIEIETKTG-----LEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFSEEFIEKRRRGL 80

                           90       100
                   ....*....|....*....|....*
gi 1955874124  225 EKYLRKLAGHPVIRK-SDEFKVFLQ 248
Cdd:smart00312  81 EKYLQSLLNHPELINhSEVVLEFLE 105

Vps5 C terminal like; Vps5 is a sorting nexin that functions in membrane trafficking. This is the C terminal dimerization domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 313 GSSKPPVVEEDKEFLEKKEKLRDFEQQLSATSQQAESLVKAQQDMAETYGELGLTLIKLTKFENEEAVFNGqrvcaadTK 392
Cdd:pfam09325  13 SKSSYKFNEPDEWFIDKKQYIDSLESQLKKLYKALELLVSQRKELASATGEFAKSLASLASLELSTGLSRA-------LS 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 393 NIATAAVKASRLYRELNAQTVKHLDV-LHDYLGLMLAVHGAFSERSSALLTEQTLLSDLSSLNTRAEKLEAAsskvfggD 471
Cdd:pfam09325  86 QLAEVEERIKELLERQALQDVLTLGEtIDEYLRLIGSVKAVFNQRVKAWQSWQNAEQELSKKKEQLEKLLRA-------N 158

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1955874124 472 KSRIQKLEQLKETIRTTEDAKNVAMREYERIKENNRSELERFDRERQADFLSMLKGFVTNQVGYAEKISDVWAKVAEE 549
Cdd:pfam09325 159 KSQNDKLQQAKKEVEELERRVQQAEKEFEDISELIKKELERFELERVDDFKNSVEIYLESAIESQKELIELWETFLPE 236

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 1955874124 129 IKITVSNPQKEqdVSNSIVPGGNSYVTYLITTRtniADFGGSEF-------SVRRRFKDVVTLSERLAESYRGFFIPPRP 201
Cdd:cd06864     1 MEITVTEAEKR--TGGSAMNLKETYTVYLIETK---IVEHESEEglskklsSLWRRYSEFELLRNYLVVTYPYVIVPPLP 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1955874124 202 DKSVVegQVMQK-------QEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd06864    76 EKRAM--FMWQKlssdtfdPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLT 127

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related 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. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/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 1955874124 128 YIKITVSNPQkeqdvsnSIVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLaESYRGFFIPPRPDKSVVE 207
Cdd:cd06894     1 FLEIDVVNPQ-------THGVGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSEL-ERDSKIVVPPLPGKALKR 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1955874124 208 GQVMQK------QEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd06894    73 QLPFRGddgifeEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQ 119

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 127 DYIKITVSNPQkeqdvsnSIVPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRgFFIPPRPDKSVV 206
Cdd:cd07294     2 NFLEIDIFNPQ-------TVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSK-IVVPPLPGKALK 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1955874124 207 EGQVMQKQE------FVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQ 248
Cdd:cd07294    74 RQLPFRGDEgifeesFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQ 121

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 1955874124 321 EEDKEFLEKKEKLRDFEQQLSATSQQAESLVKAQQDMAETYGELGLTLIKLTKFENEEAVFNgqrVCAadtkNIATAAVK 400
Cdd:cd07627     1 EPDEWFIEKKQYLDSLESQLKQLYKSLELVSSQRKELASATEEFAETLEALSSLELSKSLSD---LLA----ALAEVQKR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 401 ASRLYRELNAQTVKHLDV-LHDYLGLMLAVHGAFSERSSALLTEQTLLSDLSSLNTRAEKLEAASskvfggdKSRIQKLE 479
Cdd:cd07627    74 IKESLERQALQDVLTLGVtLDEYIRSIGSVRAAFAQRQKLWQYWQSAESELSKKKAQLEKLKRQG-------KTQQEKLN 146

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1955874124 480 QLKETIRTTEDAKNVAMREYERIKENNRSELERFDRERQADF 521
Cdd:cd07627   147 SLLSELEEAERRASELKKEFEEVSELIKSELERFERERVEDF 188

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 150 GNSYVTYLITTRTNiadfgGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVeGQVMQKQEFVEQRRLALEKYLR 229
Cdd:cd06897    12 PKPYTVYNIQVRLP-----LRSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWF-LSTSSNPKLVEERRVGLEAFLR 85

                          90       100
                  ....*....|....*....|...
gi 1955874124 230 KLAGHPV--IRKSDEFKVFLQVQ 250
Cdd:cd06897    86 ALLNDEDsrWRNSPAVKEFLNLP 108

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 1955874124 148 PGGNSYVTYLIttrtNIADFGGSEFS----VRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVeGQVMQKQEFVEQRRLA 223
Cdd:cd06876    33 EEGKEFVVYLI----EVQRLNNDDQSsgwvVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKI-SLKYSKTLLVEERRKA 107

                          90       100
                  ....*....|....*....|....
gi 1955874124 224 LEKYLRKLAGHPVIRKSDEFKVFL 247
Cdd:cd06876   108 LEKYLQELLKIPEVCEDEEFRKFL 131

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 1955874124 153 YVTYLITTRTNiadfggsEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVegqVMQKQEFVEQRRLALEKYLRKLA 232
Cdd:cd06866    18 HVEYEVSSKRF-------KSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIG---GSADREFLEARRRGLSRFLNLVA 87

                          90
                  ....*....|....*
gi 1955874124 233 GHPVIRKSDEFKVFL 247
Cdd:cd06866    88 RHPVLSEDELVRTFL 102

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 1; 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. 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network. 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 1955874124 321 EEDKEFLEKKEKLRDFEQQLSATSQQAESLVKAQQDMAETYGELGLTLIKLTKFENEEAVfngqrvcAADTKNIATAAVK 400
Cdd:cd07665    19 ESDVWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTALFAKSLAMLGSSEDNTAL-------SRALSQLAEVEEK 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1955874124 401 ASRLYRE-LNAQTVKHLDVLHDYLGLMLAVHGAFSERSSALLTEQTLLSDLsslntraEKLEAASSKVFGGDKSriQKLE 479
Cdd:cd07665    92 IEQLHQEqANNDFFLLAELLADYIRLLSAVRGAFDQRMKTWQRWQDAQAML-------QKKREAEARLLWANKP--DKLQ 162

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1955874124 480 QLKETIRTTEDAKNVAMREYERIKENNRSELERFDRERQADFLSMLKGFVTNQVGYAEKISDVW 543
Cdd:cd07665   163 QAKDEIAEWESRVTQYERDFERISATVRKEVIRFEKEKSKDFKNHIIKYLETLLHSQQQLVKYW 226

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 1955874124 131 ITVSNPQKEQDvsnsivPGGNSYVTYLITTRTNIADFGGSEFSVRRRFKDVVTLSERLAESYRGFFIPPRPDKSVVegQV 210
Cdd:cd06898     2 VEVRDPRTHKE------DDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLF--GR 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1955874124 211 MQKQEFVEQRRLALEKYLRKLAGHPVIRKSDEFKVFLQVQ 250
Cdd:cd06898    74 FNNEGFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQTQ 113