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 2217308156  44 ALRQEVDTLKRKVAEQEERqgmkVQALARENEVLK 78
Cdd:cd21936    12 AVREEVDVLKEQIAELEER----ISQLERENSLLR 42

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308156 228 EWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllasllpalpplnlqvtsevtssqDAKF 307
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY-------------------------------------NEEF 50

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217308156 308 VEERRKQLQNYLRSVMNkviqmVPEFAASP 337
Cdd:pfam00787  51 IEKRRKGLEQYLQRLLQ-----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 2217308156  44 ALRQEVDTLKRKVAEQEERqgmkVQALARENEVLK 78
Cdd:cd21936    12 AVREEVDVLKEQIAELEER----ISQLERENSLLR 42

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 2217308156 198 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaa 277
Cdd:cd06874     1 IKITIPRYVLRGQGKDEHFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGNK----------- 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308156 278 asllasllpalpplnlqvtsevtssqDAKFVEERRKQLQNYLRSVMNKVIQ-----MVPEFAASPKKETLIQLMPFFVMG 352
Cdd:cd06874    70 --------------------------SERVAKERRRQLETYLRNFFSVCLKlpacpLYPKVGRTLSKATLCDFSPFFRKG 123

                  .
gi 2217308156 353 L 353
Cdd:cd06874   124 V 124

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308156 228 EWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllasllpalpplnlqvtsevtssqDAKF 307
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY-------------------------------------NEEF 50

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217308156 308 VEERRKQLQNYLRSVMNkviqmVPEFAASP 337
Cdd:pfam00787  51 IEKRRKGLEQYLQRLLQ-----HPELRNSE 75

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 2217308156 213 NAFHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYpQVRAYNFPPKKAIGNKpppSPAwmtaaasllasllpalppln 292
Cdd:cd06875    15 EGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEH-KVDKDLLPPKKLIGNK---SPS-------------------- 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2217308156 293 lqvtsevtssqdakFVEERRKQLQNYLRSVMNKVIQMVPE 332
Cdd:cd06875    71 --------------FVEKRRKELEIYLQTLLSFFQKTMPR 96

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 2217308156 229 WNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGNKpppspawmtaaasllasllpalpplnlqvtsevtsSQDAKFV 308
Cdd:cd06876    57 WVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLK-----------------------------------YSKTLLV 101

                          90
                  ....*....|....
gi 2217308156 309 EERRKQLQNYLRSV 322
Cdd:cd06876   102 EERRKALEKYLQEL 115

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308156 201 WIPSVFLRG-------KAANAFHVYQVYIRIKDDEW---NIYRRYTEFRSLHHKLQNKYPQVRAYNFPPkkaignkPPPS 270
Cdd:cd07280     1 HATDVNVGDytivggdTGGGAYVVWKITIETKDLIGssiVAYKRYSEFVQLREALLDEFPRHKRNEIPQ-------LPPK 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2217308156 271 PAWmtaaasllasllpalpplnlqvtSEVTSSQDAKFVEERRKQLQNYLRSVM-NKVIQ 328
Cdd:cd07280    74 VPW-----------------------YDSRVNLNKAWLEKRRRGLQYFLNCVLlNPVFG 109

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 2217308156 209 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQvRAYNFPPkkaignkpPPSPAWMTAAasllas 283
Cdd:cd07281    12 GDGMNAYVVYKVTTQtsllmFRSKHFTVKRRFSDFLGLYEKLSEKHSQ-NGFIVPP--------PPEKSLIGMT------ 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2217308156 284 llpalpplNLQVTSEVTSSqdAKFVEERRKQLQNYLRSVMN 324
Cdd:cd07281    77 --------KVKVGKEDSSS--AEFLERRRAALERYLQRIVS 107

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217308156 215 FHVYQVYIRIKDDEWNIYRRYTEFRSLHHKLQNKYPQVrAYNFPPKKAIGNKPPPS 270
Cdd:cd06870    20 FTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPAS-NLKIPGKRLFGNNFDPD 74

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217308156 225 KDDEWNIYRRYTEFRSLHHKLQnkyPQVRAYNFPPKKAIGNkpppspawmtaaasllasllpalpplnlqvtsevtssQD 304
Cdd:cd06871    34 PENSWQVIRRYNDFDLLNASLQ---ISGISLPLPPKKLIGN-------------------------------------MD 73

                          90
                  ....*....|....*....
gi 2217308156 305 AKFVEERRKQLQNYLRSVM 323
Cdd:cd06871    74 REFIAERQQGLQNYLNVIL 92

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 2217308156 209 GKAANAFHVYQVYIR-----IKDDEWNIYRRYTEFRSLHHKLQNKYPQVRAYNFPPKKAIGnkpppspawmtaaasllas 283
Cdd:cd06859    12 GDGMSAYVVYRVTTKtnlpdFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVG------------------- 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2217308156 284 llpalpplnlqvtsevTSSQDAKFVEERRKQLQNYLRSVMN 324
Cdd:cd06859    73 ----------------RFKVKFEFIEKRRAALERFLRRIAA 97

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 2217308156  44 ALRQEVDTLKRKVAEQEERqgmkVQALARENEVLK 78
Cdd:cd21936    12 AVREEVDVLKEQIAELEER----ISQLERENSLLR 42