Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain; Basic leucine zipper (bZIP) factors comprise one of the most important classes of enhancer-type transcription factors. They act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes including cell survival, learning and memory, lipid metabolism, and cancer progression, among others. They also play important roles in responses to stimuli or stress signals such as cytokines, genotoxic agents, or physiological stresses. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 168823439 264 QKGYLEELvrlrESQLKDLEAENRRLQLQLEEAAAQNQREK 304
Cdd:cd14691   22 KKARMDEL----EERVRELEEENQKLRAENESLRARNEDLL 58

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 168823439   60 NFAAILEQILSHRFKACAPAGpVSWFSSDGQRGFWDYIRLACSKVPN--NCVSSIENMENISTA---RAKGRAWIRVALM 134
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLI-LRAAGLLPERSFWALLERVGKLVPPaeELLSSVQELEQIHTPyspDGRGRAWIRLALN 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 168823439  135 EKRMSEYITTALRDNRTTRRFYDSGAIMLREEAT-VLTGMLIGLSAIDFSFCLKG 188
Cdd:pfam02759  80 EKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGeILLGLLVGLSALDFNLCLKL 134

Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain; XBP1, a member of the Basic leucine zipper (bZIP) family, is the key transcription factor that orchestrates the unfolded protein response (UPR). It is the most conserved component of the UPR and is critical for cell fate determination in response to ER stress. The inositol-requiring enzyme 1 (IRE1)-XBP1 pathway is one of the three major sensors at the ER membrane that initiates the UPR upon activation. IRE1, a type I transmembrane protein kinase and endoribonuclease, oligomerizes upon ER stress leading to its increased activity. It splices the XBP1 mRNA, producing a variant that translocates to the nucleus and activates its target genes, which are involved in protein folding, degradation, and trafficking. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 168823439 264 QKGYLEELvrlrESQLKDLEAENRRLQLQLEEAAAQNQREK 304
Cdd:cd14691   22 KKARMDEL----EERVRELEEENQKLRAENESLRARNEDLL 58

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 168823439  30 NLITVCRFSVKTLLEKYTAEPIDDSSEEFVNFAAILEQILSHRFKACAPagpvsWFSSDGQRGFWDYIRLACSKVPNNCV 109
Cdd:cd17684    1 NLVTVCRLSVKSLIDKACLETIDDSSEELINFAAILEQILSHRLKPVKP-----WYGSEEPRTFWDYIRVACKKVPQNCI 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 168823439 110 SSIENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIMLREEATVLTGMLIGLSAIDFSF 184
Cdd:cd17684   76 ASIEQMENIKSPKAKGRAWIRVALMEKRLSEYLSTALKQTRLTRNFYQDGAIMLSEDATVLCGMLIGLNAIDFSF 150

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 168823439   60 NFAAILEQILSHRFKACAPAGpVSWFSSDGQRGFWDYIRLACSKVPN--NCVSSIENMENISTA---RAKGRAWIRVALM 134
Cdd:pfam02759   1 QLCAALEALLSHGLKRSSLLI-LRAAGLLPERSFWALLERVGKLVPPaeELLSSVQELEQIHTPyspDGRGRAWIRLALN 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 168823439  135 EKRMSEYITTALRDNRTTRRFYDSGAIMLREEAT-VLTGMLIGLSAIDFSFCLKG 188
Cdd:pfam02759  80 EKLLDQWLKLLLSNKELLSEYYEPWALLADPEFGeILLGLLVGLSALDFNLCLKL 134

RUN domain; RUN domain, named after RPIP8 (Rap2 interacting protein 8), UNC-14 and NESCA (new molecule containing SH3 at the carboxyl-terminus), is a less conserved protein motif that 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. RUN domains are often found in proteins linked particularly to the functions of GTPases in the Rap and Rab families, suggesting the RUN domain may be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. RUN domain-containing proteins could hence play important roles in multiple Ras-like GTPase signalling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439  38 SVKTLLEKY---------TAEPIDDSSEEFVNFAAILEQILSHRFKAcapagpvSWFSSdGQRGFWDYIRLACSKVPNN- 107
Cdd:cd17671    2 AVKELLESFadngeaddsAALTLTDDDPVVGRLCAALEAILSHGLKP-------KRFGG-GKVSFWDFLEALEKLLPAPs 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439 108 ---CVSSIENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIML-REEATVLTGMLIGLSAIDFS 183
Cdd:cd17671   74 lkqAIRDINSLSNVKTDDGRGRAWIRLALNEKSLESYLAALLSDQSLLRKYYEPWALLRdPEEAELFLSLLVGLSSLDFN 153

                 .
gi 168823439 184 F 184
Cdd:cd17671  154 L 154

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439  27 ERRNLITVCRFSVKTLLEKYT--AEPIDDSSEEFVNFAAILEQILSHRFKACApagpvswfSSDGQ-RGFWDYIRLACSK 103
Cdd:cd17696    1 ERMNLMNMAKLSIKGLIESALnlGRTLDSDYAPLQQFFVVMEHCLKHGLKAKK--------TFLGQnKSFWGPLELVEKL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439 104 VPN--NCVSSIENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIMLREEATVLTGMLIGLSAID 181
Cdd:cd17696   73 VPEaaEITASVKDLPGLKTPVGRGRAWLRLALMQKKLSEYMKALINRKDLLSEFYEPNALMMEEEGAIIAGLLVGLNVID 152

                 ....
gi 168823439 182 FSFC 185
Cdd:cd17696  153 ANFC 156

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 168823439  38 SVKTLLEKY--TAEPIDDSSEEFVNFAAILEQILSHRFKACAPAGPVSWFSSDGQRG----FWDYIRLACSKvpnNCVSS 111
Cdd:cd17679   11 SVKELQLEYvsSDEVVTSSDDGANTLCCVLEAIFLHGLKDKFISKVSSVFSGDVDKLpepnFWPLLLKFSHR---DVIDQ 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439 112 IENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIML-REEATVLTGMLIGLSAIDFSFCLKGEV 190
Cdd:cd17679   88 IEHLSQITTDVGRCRAWIRLALNDGLLESYLEAILKDKSALKSYYNPSAFLRdPEQLDILKSLLQGLESFQFELPYNSSL 167

                 .
gi 168823439 191 L 191
Cdd:cd17679  168 L 168

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 168823439  43 LEKYTAEPIDDSSEEFVNFAAILEQILSHRFKAcapagPVSWFSsdGQRGFWDYIR-LA--CSKVP---NNCVSSIENME 116
Cdd:cd17682    9 LKSEFGEITDPDNPYLRPFCETLEKILRKGLKE-----KVSLGG--RRKDYWDWLEeLLkkLNKIPkslSDAVKFVKSCK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 168823439 117 NISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIMLREE-ATVLTGMLIGLSAIDFSF 184
Cdd:cd17682   82 KVKTNQGRGRLFIRYALNKKCLHDPVQQLVKNPKLLSDYYSPDSILGNEIlSEILLSLLYQLNEINFDL 150

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 168823439  65 LEQILSHRFKacapagpvswfssDGQRGFWDYIRLACSKvpnNCVSSIENMENISTARAKGRAWIRVALMEKRMSEYITT 144
Cdd:cd17680   41 LDHALLHGLR-------------RGNRGYWPFVKEFTHK---ETIKQIENLPNVTTDLGRGRAWLYLALNEGSLESYLRS 104

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 168823439 145 ALRDNRTTRRFYDSGAIMLREEA-TVLTGMLIGLSAIDFSF 184
Cdd:cd17680  105 FLENRKLVKKFYHKHALLRDSQRlELLLTLLSGLEFVQFDL 145

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 168823439 112 IENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIM-LREEATVLTGMLIGLSAIDFsFCL 186
Cdd:cd17691  127 IQNMSEIKTDVGRARAWIRLSLEKKLLSQHLKQLLSNQALTKKLYKRYAFLrCEEEKEQFLYHLLSLNAVDY-FCF 201

RUN domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; 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. RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain; this model represents the RUN domain of RUFY4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 168823439  50 PIDDSSEEFVNFAAILEQILSHRFKAcapagPVSWFSSdgQRGFWDYIR--LACSKVPNNCVSSIENMENISTARAKGRA 127
Cdd:cd17697   20 PITDGSPELHRLCARLEYLLQFDQKE-----KKSFFGS--RKDYWDFLClcLNRHRGGTEGIHFVNSTDKLKTPLGKGRA 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 168823439 128 WIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIMLREEATV-LTGMLIGLSAIDF 182
Cdd:cd17697   93 FIRYCLVQQQLAESLQLCLLNPELTGEWYYARSPFLSPELRSdILDSLYELNGVNF 148

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 168823439 112 IENMENISTARAKGRAWIRVALMEKRMSEYITTALRDNRTTRRFYDSGAIM-LREEATVLTGMLIGLSAIDFsFCL 186
Cdd:cd17690  130 IQNIGEIKTDVGKARAWVRLSMEKKLLSRHLKQLLSDHELTKKLYKRYAFLrCDDEKEQFLYHLLSFNAVDY-FCF 204

Basic leucine zipper (bZIP) domain of X-box binding protein 1 (XBP1) and similar proteins: a DNA-binding and dimerization domain; XBP1, a member of the Basic leucine zipper (bZIP) family, is the key transcription factor that orchestrates the unfolded protein response (UPR). It is the most conserved component of the UPR and is critical for cell fate determination in response to ER stress. The inositol-requiring enzyme 1 (IRE1)-XBP1 pathway is one of the three major sensors at the ER membrane that initiates the UPR upon activation. IRE1, a type I transmembrane protein kinase and endoribonuclease, oligomerizes upon ER stress leading to its increased activity. It splices the XBP1 mRNA, producing a variant that translocates to the nucleus and activates its target genes, which are involved in protein folding, degradation, and trafficking. bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 168823439 264 QKGYLEELvrlrESQLKDLEAENRRLQLQLEEAAAQNQREK 304
Cdd:cd14691   22 KKARMDEL----EERVRELEEENQKLRAENESLRARNEDLL 58