RUN domain found in sorting nexin-29 (SNX29) and similar proteins; SNX29, also called RUN domain-containing protein 2A (RUNDC2A), belongs to the sorting nexin family. Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain, a phospholipid-binding motif, or through protein-protein interactions with membrane-associated protein complexes. Some sorting nexin family members have been shown to facilitate protein sorting. This model contains the RUN domain of SNX29.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689    1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689   81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                 ....*.
gi 530409379 183 FAINID 188
Cdd:cd17689  161 FALSID 166

leucine zipper found in the TSC22 domain leucine zipper transcription factors, c-Myc-binding protein, and similar proteins; The family includes TGF-beta-stimulated clone-22 domain (TSC22D) leucine zipper transcription factors, TSC22D1-4, as well as c-Myc-binding protein (MycBP). TSC22D proteins have diverse physiological functions, including cell growth, development, homeostasis, and immune regulation. MycBP, also called associate of Myc 1 (AMY-1), is a novel c-Myc binding protein that may control the transcriptional activity of Myc. It stimulates the activation of E box-dependent transcription by Myc. Members of this family contain a conserved leucine zipper (ZIP) domain. Its first helix is not basic and does not contain the consensus sequence, NXX(A)(A)XX(C/S)R, found in most basic region/leucine zipper (bZIP) proteins. In the bZIP family of transcription factors, the leucine zipper acts as a dimerization domain and the upstream basic region as a DNA-binding domain. However, DNA-binding capability of TSC22D family proteins is not obvious, due to the lack of the basic region found in the original bZIP DNA-binding domains. Similar to bZIP, ZIP forms homo- and heterodimers, resulting in many dimers that may have different effects on transcription.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 530409379 514 ALRQEVDTLKRKVAEQEERqgmkVQALARENEVLK 548
Cdd:cd21936   12 AVREEVDVLKEQIAELEER----ISQLERENSLLR 42

RUN domain found in sorting nexin-29 (SNX29) and similar proteins; SNX29, also called RUN domain-containing protein 2A (RUNDC2A), belongs to the sorting nexin family. Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain, a phospholipid-binding motif, or through protein-protein interactions with membrane-associated protein complexes. Some sorting nexin family members have been shown to facilitate protein sorting. This model contains the RUN domain of SNX29.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689    1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689   81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                 ....*.
gi 530409379 183 FAINID 188
Cdd:cd17689  161 FALSID 166

RUN domain; This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could hence play important roles in multiple Ras-like GTPase signalling pathways. The domain is comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379   54 CLCAQFEAVLQHGLKRSRGLALTAAAIKQaagfasktetEPVFWYYVKEV-----LNKHELQRFYSLRHI---ASDVGRG 125
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLILRAAGLLP----------ERSFWALLERVgklvpPAEELLSSVQELEQIhtpYSPDGRG 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530409379  126 RAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAINIDN 189
Cdd:pfam02759  71 RAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCLKL 134

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530409379  698 EWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNkviqmVPEFAASP 770
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQ-----HPELRNSE 75

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 703 RRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNK-----DAKFVEERRKQLQNYLRSVM----------NKVIQMVPEFA 767
Cdd:COG5391  177 RRYSDFESLHSILIKLLPLCAIPPLPSKKSNSEYygdrfSDEFIEERRQSLQNFLRRVSthpllsnyknSKSWESHSTLL 256

                         90       100       110
                 ....*....|....*....|....*....|
gi 530409379 768 ASPKKETLIQLMPFFVDITPPGEPVNSRPK 797
Cdd:COG5391  257 SSFIENRKSVPTPLSLDLTSTTQELDMERK 286

RUN domain found in sorting nexin-29 (SNX29) and similar proteins; SNX29, also called RUN domain-containing protein 2A (RUNDC2A), belongs to the sorting nexin family. Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain, a phospholipid-binding motif, or through protein-protein interactions with membrane-associated protein complexes. Some sorting nexin family members have been shown to facilitate protein sorting. This model contains the RUN domain of SNX29.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689    1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689   81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                 ....*.
gi 530409379 183 FAINID 188
Cdd:cd17689  161 FALSID 166

RUN domain; This domain is present in several proteins that are linked to the functions of GTPases in the Rap and Rab families. They could hence play important roles in multiple Ras-like GTPase signalling pathways. The domain is comprises six conserved regions, which in some proteins have considerable insertions between them. The domain core is thought to take up a predominantly alpha fold, with basic amino acids in regions A and D possibly playing a functional role in interactions with Ras GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379   54 CLCAQFEAVLQHGLKRSRGLALTAAAIKQaagfasktetEPVFWYYVKEV-----LNKHELQRFYSLRHI---ASDVGRG 125
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLILRAAGLLP----------ERSFWALLERVgklvpPAEELLSSVQELEQIhtpYSPDGRG 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530409379  126 RAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAINIDN 189
Cdd:pfam02759  71 RAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCLKL 134

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; 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. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. 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 530409379 668 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 747
Cdd:cd06874    1 IKITIPRYVLRGQGKDEHFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGNKSERVAKERRRQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 530409379 748 LQNYLRSVMNKVIQ-----MVPEFAASPKKETLIQLMPFF 782
Cdd:cd06874   81 LETYLRNFFSVCLKlpacpLYPKVGRTLSKATLCDFSPFF 120

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 530409379 669 NVWIPSVFLRGKAANAFHVYQVYIRIKD-DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ 747
Cdd:cd06093    1 SVSIPDYEKVKDGGKKYVVYIIEVTTQGgEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERRKQ 80

                         90
                 ....*....|
gi 530409379 748 LQNYLRSVMN 757
Cdd:cd06093   81 LEQYLQSLLN 90

domain involved in Ras-like GTPase signaling;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530409379   125 GRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAINID 188
Cdd:smart00593   1 FRAWIRLALNEKLLSSWLNLLLSDEELLSKYYEPWAFLRDPEEGEQLLGLLVGLSALDFNLPVD 64

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 683 NAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYpQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNKVIQM 762
Cdd:cd06875   15 EGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEH-KVDKDLLPPKKLIGNKSPSFVEKRRKELEIYLQTLLSFFQKT 93

                 ...
gi 530409379 763 VPE 765
Cdd:cd06875   94 MPR 96

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 530409379 684 AFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVMNKViqmv 763
Cdd:cd06873   26 AISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPE---- 101

                         90
                 ....*....|...
gi 530409379 764 pEFAASPKKETLI 776
Cdd:cd06873  102 -VLDANPGLQEIV 113

RUN domain found in RUN domain-containing protein 3 (RUNDC3) and similar proteins; RUNDC3 contains two isoforms, RUNDC3A and RUNDC3B. RUNDC3A, also called Rap2-interacting protein 8 (RPIP8), may act as an effector of Rap2A GTPase in neuronal cells. RUNDC3B, also called Rap2-binding protein 9, or Rap2-interacting protein 9 (RPIP-9), contains a RUN domain in its N-terminal region that mediates interaction with Rap2, an important component of the Mitogen-Activated Protein Kinase (MAPK) cascade, which regulates cellular proliferation and differentiation. It also contains characteristic binding sites for MAPK intermediates. Both RUNDC3A and RUNDC3B contain a RUN domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  43 EIASDSDSRVTCLCAQFEAVLQHGLKrsrglaltaaAIKQAAGfaskTETEPVFWYYVKEVLNK---HELQRFYSLRHIA 119
Cdd:cd17684   20 ETIDDSSEELINFAAILEQILSHRLK----------PVKPWYG----SEEPRTFWDYIRVACKKvpqNCIASIEQMENIK 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530409379 120 SDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEErSSMLPTMAAGLNSILF 183
Cdd:cd17684   86 SPKAKGRAWIRVALMEKRLSEYLSTALKQTRLTRNFYQDGAIMLSED-ATVLCGMLIGLNAIDF 148

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530409379 695 KDDEWNIYRRYTEFRSLHHKLQnkyPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRSVM 756
Cdd:cd06871   34 PENSWQVIRRYNDFDLLNASLQ---ISGISLPLPPKKLIGNMDREFIAERQQGLQNYLNVIL 92

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 530409379 685 FHVYQVYIRIKDDEWN----IYRRYTEFRSLHHKLQNKYPQ-VRAYNFPPKKAIGNKDAKFVEERRKQLQNYLRsvmnkV 759
Cdd:cd07279   18 YVVYQLAVVQTGDPDTqpafIERRYSDFLKLYKALRKQHPQlMAKVSFPRKVLMGNFSSELIAERSRAFEQFLG-----H 92

                         90
                 ....*....|.
gi 530409379 760 IQMVPEFAASP 770
Cdd:cd07279   93 ILSIPNLRDSK 103

RUN domain found in RUN domain-containing protein 3B (RUNDC3B) and similar proteins; RUN domain-containing protein 3B (RUNDC3B), also called Rap2-binding protein 9, or Rap2-interacting protein 9 (RPIP-9), contains a RUN domain in its N-terminal region that mediates interaction with Rap2, an important component of the Mitogen-Activated Protein Kinase (MAPK) cascade, which regulates cellular proliferation and differentiation. It also contains characteristic binding sites for MAPK intermediates. RUNDC3B contains a RUN domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  43 EIASDSDSRVTCLCAQFEAVLQHGLKrsrglaltaaaiKQAAGFAskTETEPVFWYYVKEVLNK--HE-LQRFYSLRHIA 119
Cdd:cd17700   20 ETIDDSSPEFVNFAAILEQILSHRLK------------GQVTWFG--YESPRSFWDYIRVACSKvpHNcICSIENMENVS 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530409379 120 SDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEErSSMLPTMAAGLNSILFA 184
Cdd:cd17700   86 SSRAKGRAWIRVALMEKRLSEYISTALRDFKTTRRFYEDGAIVLGEE-ANMLAGMLLGLNAIDFS 149

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 530409379 679 GKAANAFHVYQVYIRIKD-----DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQLQNYLR 753
Cdd:cd06861   12 GDLTSAHTVYTVRTRTTSpnfevSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNFVEQRRAALEKMLR 91

                         90
                 ....*....|....
gi 530409379 754 SVMNK-VIQMVPEF 766
Cdd:cd06861   92 KIANHpVLQKDPDF 105

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 530409379 683 NAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAK--FVEERRKQLQNYLRSV 755
Cdd:cd06859   16 SAYVVYRVTTKtnlpdFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVKfeFIEKRRAALERFLRRI 95

                 ..
gi 530409379 756 MN 757
Cdd:cd06859   96 AA 97

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530409379 685 FHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPPKKAIGNK-DAKFVEERRKQLQNYLRSVM 756
Cdd:cd06870   20 FTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPAS-NLKIPGKRLFGNNfDPDFIKQRRAGLDEFIQRLV 91

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 530409379 679 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPP----------KKAIGNKDA---KF 740
Cdd:cd07282   12 GDGMNAYMAYRVTTKtslsmFSRSEFSVRRRFSDFLGLHSKLASKYLHV-GYIVPPapeksivgmtKVKVGKEDSsstEF 90

                         90       100
                 ....*....|....*....|....*.
gi 530409379 741 VEERRKQLQNYL-RSVMNKVIQMVPE 765
Cdd:cd07282   91 VEKRRAALERYLqRTVKHPTLLQDPD 116

RUN domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; RUFY2, also called Rab4-interacting protein related, is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. This model represents the RUN domain of RUFY2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 122 VGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEErSSMLPTMAAGLNSI 181
Cdd:cd17695   93 LGRARAWLRLALMQKKLADYLRCLIIRRDLLSEFYEYHALMMEEE-GAVIVGLLVGLNVI 151

RUN domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also called FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homolog of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between; this model represents the RUN domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  58 QFEAVLQHGLKRsrGLALTAAAIKQAAGFASKTEtepvfwyyVKEVLNKHELQRFYSLRH---IASDVGRGRAWLRCALN 134
Cdd:cd17694   36 QFFVVLEHCLKH--GLKVKKSFIGQNKSFFGPLE--------LVEKLCPEASDIATSARNlpeLKTAVGRGRAWLHLALM 105

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 530409379 135 EHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLpTMAAGLNSI 181
Cdd:cd17694  106 QKKLADYLKVLIDRKDLLSEFYEPGALMMEEEGAVIV-GLLVGLNVI 151

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 530409379 679 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQvRAYNFPP----------KKAIGNKD---AKF 740
Cdd:cd07281   12 GDGMNAYVVYKVTTQtsllmFRSKHFTVKRRFSDFLGLYEKLSEKHSQ-NGFIVPPppeksligmtKVKVGKEDsssAEF 90

                         90
                 ....*....|....*..
gi 530409379 741 VEERRKQLQNYLRSVMN 757
Cdd:cd07281   91 LERRRAALERYLQRIVS 107

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 688 YQVY-IRIKDDE---WNIYRRYTEFRSLHHKLQnKYPQVrAYNFPPKKAIGNK-DAKFVEERRKQLQNYLRSVMnkVIQM 762
Cdd:cd06872   18 FAVYsVAVTDNEnetWVVKRRFRNFETLHRRLK-EVPKY-NLELPPKRFLSSSlDGAFIEERCKLLDKYLKDLL--VIEK 93

                 ....*
gi 530409379 763 VPEFA 767
Cdd:cd06872   94 VAESH 98

RUN domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar proteins; RUFY3, also called Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. This model represents the RUN domain of RUFY3.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530409379 118 IASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEErSSMLPTMAAGLNSI 181
Cdd:cd17696   89 LKTPVGRGRAWLRLALMQKKLSEYMKALINRKDLLSEFYEPNALMMEEE-GAIIAGLLVGLNVI 151

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 686 HVYQVYIRIKDDEWN-----IYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKaignkdaKFVEER-RKQLQNYLRSVMNkv 759
Cdd:cd06869   32 HHYEFIIRVRREGEEyrtiyVARRYSDFKKLHHDLKKEFPGKKLPKLPHKD-------KLPREKlRLSLRQYLRSLLK-- 102

                         90
                 ....*....|.
gi 530409379 760 iqmVPEFAASP 770
Cdd:cd06869  103 ---DPEVAHSS 110

RUN1 domain found in DENN domain-containing protein 5 (DENND5) and similar proteins; DENND5 has been characterized as Rab6-interacting protein which is composed of an N-terminal DENN (Differentially Expressed in Normal and Neoplastic cells) domain followed by two RUN (RPIP8 [RaP2-interacting protein 8], UNC-14, and NESCA [new molecule containing SH3 at the carboxyl terminus]) domains flanking a PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain. It functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. DENND5 has two isoforms, DENND5A and DENND5B. This model represents the first RUN domain of DENND5.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379  52 VTCLCAQFEAVLQHGLKRSRGLALTAAAIKqaAGFASKTETEPV---FWYYVKEVLNKHElqrfyslrhIASDVGRGRAW 128
Cdd:cd17677   52 IASLCDLLERIWSHGLQTKQGKSALWSHLL--AYQENEERLKPLpesLLFDMKNVQNMKE---------IKTDVGYARAW 120

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 530409379 129 LRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVM-DEERSSML 171
Cdd:cd17677  121 IRLALEKKLLSKHLKTLLSNQDLLRSLYKRYAFLRcEDEREQFL 164

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 701 IYRRYTEFRSLHHKLQNKYPQV--RAYNFPP---KKAIGNKDAKFVEERRKQLQNYLRSVMNkviqmVPEFAASPkketl 775
Cdd:cd07288   40 VWKRYSDLKKLHGELAYTHRNLfrRQEEFPPfprAQVFGRFEAAVIEERRNAAEAMLLFTVN-----IPALYNSP----- 109

                 ....*....
gi 530409379 776 iQLMPFFVD 784
Cdd:cd07288  110 -QLKEFFRD 117

RUN1 domain found in DENN domain-containing protein 5B (DENND5B) and similar proteins; DENND5B, also called Rab6-interacting protein 1 (Rab6IP1)-like protein, functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. It is composed of an N-terminal DENN (Differentially Expressed in Normal and Neoplastic cells) domain followed by two RUN (RPIP8 [RaP2-interacting protein 8], UNC-14, and NESCA [new molecule containing SH3 at the carboxyl terminus]) domains flanking a PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain. This model represents the first RUN domain of DENND5B.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530409379 107 HELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVM-DEERSSML 171
Cdd:cd17691  122 QDMRHIQNMSEIKTDVGRARAWIRLSLEKKLLSQHLKQLLSNQALTKKLYKRYAFLRcEEEKEQFL 187

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530409379 701 IYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKDAKFVEERRKQ-LQNYLRSVMnkviQMVPEFAAS 769
Cdd:cd06884   36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQdIQQFLNSLF----KMAEEVSHS 101