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 2462551619  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689     1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689    81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                  ....*.
gi 2462551619 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 2462551619 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 2462551619  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689     1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689    81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                  ....*.
gi 2462551619 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 2462551619  54 CLCAQFEAVLQHGLKRSRGLALTAAAIKQaagfasktetEPVFWYYVKEV-----LNKHELQRFYSLRHIAS---DVGRG 125
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLILRAAGLLP----------ERSFWALLERVgklvpPAEELLSSVQELEQIHTpysPDGRG 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462551619 126 RAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAINIDN 189
Cdd:pfam02759  71 RAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCLKL 134

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 698 EWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllasllpalpplnlqDAKFVEERRKQLQ 777
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY----------------------------NEEFIEKRRKGLE 59

                          90       100
                  ....*....|....*....|.
gi 2462551619 778 NYLRSVMNkviqmVPEFAASP 798
Cdd:pfam00787  60 QYLQRLLQ-----HPELRNSE 75

leucine zipper domain found in the TSC22 domain family of leucine zipper transcription factors; The TGF-beta-stimulated clone-22 domain (TSC22D) family includes TSC22D1-4 and similar proteins. They have diverse physiological functions, including cell growth, development, homeostasis, and immune regulation. All family members contain a conserved leucine zipper (ZIP) domain located at the C-terminus. 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 2462551619 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 2462551619  26 RLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRGLALTAAAIKQA---AGFASKTETEPVFWYYVKE 102
Cdd:cd17689     1 RLLDAVKQCQIRFGGKTELATESDSRVSCLCAQLEAVLQHGLKTSRSPNLVSSAVTQVsglAGSLGSAETEPTFWPFVKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 103 VLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSIL 182
Cdd:cd17689    81 HLTKHELERFELLKNIWTDIGRGRAWLRSALNEHSLERYLHILLSNENLLRQYYEDWAFLRDEERSSMLPNMAAGLGSIL 160

                  ....*.
gi 2462551619 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 2462551619  54 CLCAQFEAVLQHGLKRSRGLALTAAAIKQaagfasktetEPVFWYYVKEV-----LNKHELQRFYSLRHIAS---DVGRG 125
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLILRAAGLLP----------ERSFWALLERVgklvpPAEELLSSVQELEQIHTpysPDGRG 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462551619 126 RAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAINIDN 189
Cdd:pfam02759  71 RAWIRLALNEKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGEILLGLLVGLSALDFNLCLKL 134

RUN domain found in pleckstrin homology domain-containing family M member 1 (PLEKHM1) and similar proteins; PLEKHM1, also called PH domain-containing family M member 1, or 162 kDa adapter protein (AP162), may act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. This model represents the RUN domain of PLEKHM1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619  23 LLERLLDAVKQCQIRFGGRKEIASDSDSRVTCLCAQFEAVLQHGLKRSRglaltaaAIKQAAGFASKTE--TEPVFWYYV 100
Cdd:cd17679     4 LTKELSSSVKELQLEYVSSDEVVTSSDDGANTLCCVLEAIFLHGLKDKF-------ISKVSSVFSGDVDklPEPNFWPLL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 101 KEVLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNS 180
Cdd:cd17679    77 LKFSHRDVIDQIEHLSQITTDVGRCRAWIRLALNDGLLESYLEAILKDKSALKSYYNPSAFLRDPEQLDILKSLLQGLES 156

                         170
                  ....*....|...
gi 2462551619 181 ILFAINIDNKDLN 193
Cdd:cd17679   157 FQFELPYNSSLLN 169

RUN domain found in pleckstrin homology domain-containing family M member 2 (PLEKHM2) and similar proteins; PLEKHM2, also called PH domain-containing family M member 2, or Salmonella-induced filaments A (SifA) and Kinesin-Interacting Protein (SKIP), is the lysosome, melanosome and lytic granule cargo adaptor that controls lysosome positioning using a composite kinesin-1 heavy and light chain-binding domain. In addition to kinesin-1, it also interacts with several Rabs to affect endosomal trafficking. This model represents the RUN domain of PLEKHM2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619  22 FLLERLLDAVKQCQIRFGGRKEIASDSDSR---VTCLCAQFEAVLQHGLKRSRGLaltaaaikqaagfasktetepvFWY 98
Cdd:cd17680     1 RILRNISEAIKSLQSYSSSQEEEDVLITNEnreLQRLCEALDHALLHGLRRGNRG----------------------YWP 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619  99 YVKEVLNKHELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGL 178
Cdd:cd17680    59 FVKEFTHKETIKQIENLPNVTTDLGRGRAWLYLALNEGSLESYLRSFLENRKLVKKFYHKHALLRDSQRLELLLTLLSGL 138

                  ....*.
gi 2462551619 179 NSILFA 184
Cdd:cd17680   139 EFVQFD 144

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 2462551619 669 NVWIPSVFLRGKAANAFHVYQVYIRIKD-DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaa 747
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVVYIIEVTTQGgEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNL----------- 69

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462551619 748 asllasllpalpplnlqDAKFVEERRKQLQNYLRSVMN 785
Cdd:cd06093    70 -----------------DPEFIEERRKQLEQYLQSLLN 90

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 2462551619  683 NAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNkpppspawmtaaasllasllpalppLN 762
Cdd:smart00312  12 HYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGR-------------------------LN 66

                           90       100
                   ....*....|....*....|...
gi 2462551619  763 LQDAKFVEERRKQLQNYLRSVMN 785
Cdd:smart00312  67 NFSEEFIEKRRRGLEKYLQSLLN 89

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 2462551619 685 FHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYpQVRAYNFPPKKAIGNKpppSPAwmtaaasllasllpalpplnlq 764
Cdd:cd06875    17 YTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEH-KVDKDLLPPKKLIGNK---SPS---------------------- 70

                          90       100
                  ....*....|....*....|....*....
gi 2462551619 765 dakFVEERRKQLQNYLRSVMNKVIQMVPE 793
Cdd:cd06875    71 ---FVEKRRKELEIYLQTLLSFFQKTMPR 96

RUN domain found in RUN and FYVE domain-containing proteins, RUFY1, RUFY2, RUFY3 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1, RUFY2, and RUFY3. 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. RUFY2, also called Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. 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. RUFY1, RUFY2, and RUFY3 contain 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 2462551619  55 LCAQFEAVLQHGLKRSRglaltaaaikqaagfaSKTETEPVFWYyVKEVLNKH--ELQRFYS----LRHIASDVGRGRAW 128
Cdd:cd17681    37 FFVILEHVLRHGLKVKK----------------SFLGPNKSFWP-VLEHVEKLvpEANEITAsvrdLPGIKTPLGRARAW 99

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462551619 129 LRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEE 166
Cdd:cd17681   100 LRLALMQKKLADYFRALIENKDLLSEFYEPGALMMSEE 137

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 2462551619 683 NAFHVYQVYI-RIKDDE----WNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllasllpa 757
Cdd:cd06876    36 KEFVVYLIEVqRLNNDDqssgWVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLK--------------------- 94

                          90       100
                  ....*....|....*....|....*.
gi 2462551619 758 lpplnLQDAKFVEERRKQLQNYLRSV 783
Cdd:cd06876    95 -----YSKTLLVEERRKALEKYLQEL 115

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 2462551619 672 IPSVFLRGKAanaFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKaignkpppspaWMtaaasll 751
Cdd:cd06897     5 IPTTSVSPKP---YTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKS-----------WF------- 63

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462551619 752 asllpalpPLNLQDAKFVEERRKQLQNYLRSVMN 785
Cdd:cd06897    64 --------LSTSSNPKLVEERRVGLEAFLRALLN 89

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 2462551619  58 QFEAVLQHGLKRsrGLALTAAAIKQAAGFASKTEtepvfwyyVKEVLNKHELQRFYSLRH---IASDVGRGRAWLRCALN 134
Cdd:cd17694    36 QFFVVLEHCLKH--GLKVKKSFIGQNKSFFGPLE--------LVEKLCPEASDIATSARNlpeLKTAVGRGRAWLHLALM 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462551619 135 EHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLpTMAAGLNSI 181
Cdd:cd17694   106 QKKLADYLKVLIDRKDLLSEFYEPGALMMEEEGAVIV-GLLVGLNVI 151

RUN domain found in Run domain Beclin-1-interacting and cysteine-rich domain-containing protein (RUBCN) and similar proteins; RUBCN, also called rubicon, or beclin-1 associated RUN domain containing protein (Baron), is part of a Beclin-1-Vps34-containing autophagy complex. It negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process. It is also an important negative regulator of the innate immune response, enhances viral replication and may play a role in viral immune evasion. This model contains the RUN domain of RUBCN.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619  55 LCAQFEAVLQHGLKRSRGLaltaaaikqaagfasktETEPVFWYYVKEV--------LNKHELQRFYSLRHIASDVGRgr 126
Cdd:cd17686    24 LCRAVENILQHGLKEFQGL-----------------NKEIDDWEFVQGLrwlqptlaPSIEQQSRSSPSESEVSDKGR-- 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462551619 127 AWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSML 171
Cdd:cd17686    85 LWLRQSLQQHCLSSQLQWLVSDKELLRKYYEDEAFLRQEGYATAL 129

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 2462551619 685 FHVYQVYIRIKDDEWNI---------YRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAignkpppSPAWmtaaasllasll 755
Cdd:cd06864    23 YTVYLIETKIVEHESEEglskklsslWRRYSEFELLRNYLVVTYPYVIVPPLPEKRA-------MFMW------------ 83

                          90       100
                  ....*....|....*....|....*...
gi 2462551619 756 pALPPLNLQDAKFVEERRKQLQNYLRSV 783
Cdd:cd06864    84 -QKLSSDTFDPDFVERRRAGLENFLLRV 110

RUN domain found in RUN and FYVE domain-containing protein 4 (RUFY4), FYVE and coiled-coil domain-containing protein 1 (FYCO1), and similar proteins; The family includes RUFY4 and FYCO1. RUFY4 acts as a positive regulator that enhances autophagy and lysosome tethering in response to Interleukin-4. It is expressed in a cell-specific manner or under specific immunological conditions associated with IL4 expression such as allergic asthma. FYCO1, also called zinc finger FYVE domain-containing protein 7 (ZFYVE7), is a multidomain autophagy adaptor protein that interacts with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7, and phosphatidylinositol 3-phosphate (PI3P), to mediate microtubule plus-end-directed autophagosome transport. Both RUFY4 and FYCO1 contain 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 2462551619  55 LCAQFEAVLQHGLKRSRGLALTaaaikqaagfasktetEPVFWYYVKEVLNKHELqRFYSLRHIASDV----------GR 124
Cdd:cd17682    27 FCETLEKILRKGLKEKVSLGGR----------------RKDYWDWLEELLKKLNK-IPKSLSDAVKFVksckkvktnqGR 89

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462551619 125 GRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVMDEERSSMLPTMAAGLNSILFAI 185
Cdd:cd17682    90 GRLFIRYALNKKCLHDPVQQLVKNPKLLSDYYSPDSILGNEILSEILLSLLYQLNEINFDL 150

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 2462551619 679 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPPkkaignKPPPSPAWMTaaasllas 753
Cdd:cd07282    12 GDGMNAYMAYRVTTKtslsmFSRSEFSVRRRFSDFLGLHSKLASKYLHV-GYIVPP------APEKSIVGMT-------- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2462551619 754 lLPALPPLNLQDAKFVEERRKQLQNYL-RSVMNKVIQMVPE 793
Cdd:cd07282    77 -KVKVGKEDSSSTEFVEKRRAALERYLqRTVKHPTLLQDPD 116

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462551619 685 FHVYQVYIRIKDDEWN----IYRRYTEFRSLHHKLQNKYPQ-VRAYNFPPKKAIGN 735
Cdd:cd07279    18 YVVYQLAVVQTGDPDTqpafIERRYSDFLKLYKALRKQHPQlMAKVSFPRKVLMGN 73

RUN domain found in small G protein signaling modulators, SGSM1, SGSM2, and similar proteins; SGSM1, also called RUN and TBC1 domain-containing protein 2 (RUTBC2), interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others. It is a Rab9A effector and GTPase-activating protein for Rab36, and links Rab9A function to Rab36 function in the endosomal system. SGSM2, also called RUN and TBC1 domain-containing protein 1 (RUTBC1), is a GTPase-activating protein for Rab32/38, and regulates melanogenic enzyme trafficking in melanocytes. It also acts as a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. This model contains the RUN domain of SGSM1 and SGSM2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619  31 VKQCQIRFGGRKEIASDSdSRVTCLCAQFEAVLQHGL-KRSRGL---ALTAAAIKQAAgfASKTETEPVFwYYVKEVLNK 106
Cdd:cd17687     3 VKQLMEEAVTRKFIHEDS-SSVTSLCGAVDACLLHGLrKRALGLfrsSSTFSLLQKVA--KSCPPAADIL-RKVQEIENL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 107 HELQRFYSLRHIASDVGRGRA-------WLRCALNEHSLERYLHMLLAdrcRLSTFYEDWSFVMDEERSSMLPTMAAGLN 179
Cdd:cd17687    79 SENKRSSSSSGSNSSNSHGNSssnrkilWIRIALFEKVLDKIVDYLVE---NASKYYEKEALMADPVDGPLLASLLVGPC 155

                  ....
gi 2462551619 180 SILF 183
Cdd:cd17687   156 ALDY 159

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 2462551619 679 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQvRAYNFPPkkaignkpPPSPAWMtaaasllAS 753
Cdd:cd07281    12 GDGMNAYVVYKVTTQtsllmFRSKHFTVKRRFSDFLGLYEKLSEKHSQ-NGFIVPP--------PPEKSLI-------GM 75

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462551619 754 LLPALPPLNLQDAKFVEERRKQLQNYLRSVMN 785
Cdd:cd07281    76 TKVKVGKEDSSSAEFLERRRAALERYLQRIVS 107

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 2462551619 679 GKAANAFHVYQVYIRIKD-----DEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllas 753
Cdd:cd06861    12 GDLTSAHTVYTVRTRTTSpnfevSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRF----------------- 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2462551619 754 llpalpplnlqDAKFVEERRKQLQNYLRSVMNK-VIQMVPEF 794
Cdd:cd06861    75 -----------DDNFVEQRRAALEKMLRKIANHpVLQKDPDF 105

RUN1 domain found in DENN domain-containing protein 5A (DENND5A) and similar proteins; DENND5A, also called Rab6-interacting protein 1 (Rab6IP1), is present predominantly in developing neuronal tissue, and 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 DENND5A.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462551619 107 HELQRFYSLRHIASDVGRGRAWLRCALNEHSLERYLHMLLADRCRLSTFYEDWSFVM-DEERSSML 171
Cdd:cd17690   125 QDMRHIQNIGEIKTDVGKARAWVRLSMEKKLLSRHLKQLLSDHELTKKLYKRYAFLRcDDEKEQFL 190

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462551619 699 WNIYRRYTEFRSLHHKLQNKYPQVRAYNFppkkaignkPPPSPAWMtaaasllasllpalpplNLQDAKFVEERRKQLQN 778
Cdd:cd06878    50 WVVTRKLSEFHDLHRKLKECSSWLKKVEL---------PSLSKKWF-----------------KSIDKKFLDKSKNQLQK 103

                  ....*.
gi 2462551619 779 YLRSVM 784
Cdd:cd06878   104 YLQFIL 109

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 2462551619 701 IYRRYTEFRSLHHKLQNKyPQVRaynfppkKAIGNKPPPSpaWMtaaasllasllPALPPLNLqDAKFVEERRKQLQNYL 780
Cdd:cd06893    53 VNRRFREFLTLQTRLEEN-PKFR-------KIMNVKGPPK--RL-----------FDLPFGNM-DKDKIEARRGLLETFL 110

                          90
                  ....*....|....*...
gi 2462551619 781 RSVMNkviqmVPEFAASP 798
Cdd:cd06893   111 RQLCS-----IPEISNSE 123