Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   6 KQGEVFLQHQKH-GEKWKRYWLALHPASRHGIARLELSEAiQERSTV--VVRRHPERKVIRLADCVSVvkLPPHAEACPG 82
Cdd:cd14676    1 KEGQLYLQQQKFfGKKWRKFWAVLYPASPCGVARLEFFEG-KGGPSGgkPSKRESDRKVIRLSDCVSV--APAGGESSPP 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 528468648  83 ENMAAFCVETEEKRLVFAAERESCGEWVNIICNIAF 118
Cdd:cd14676   78 RDTAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   6 KQGEVFLQHQKH-GEKWKRYWLALHPASRHGIARLELSEAiQERSTV--VVRRHPERKVIRLADCVSVvkLPPHAEACPG 82
Cdd:cd14676    1 KEGQLYLQQQKFfGKKWRKFWAVLYPASPCGVARLEFFEG-KGGPSGgkPSKRESDRKVIRLSDCVSV--APAGGESSPP 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 528468648  83 ENMAAFCVETEEKRLVFAAERESCGEWVNIICNIAF 118
Cdd:cd14676   78 RDTAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Phosphotyrosine-binding domain (IRS1-like);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   145 SEFKVVVLQSDASVRCGLKGQYWLQ-TGEDMLLIQDLDTRRTVMEWPYKLLRRYGRDKMLFSIEAGRRCESGPGTFNFET 223
Cdd:smart00310   1 KQFWVTIRKTEGLERCPLSGSYRLRlTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQT 80

                           90
                   ....*....|....*....
gi 528468648   224 QQSEEILRLIESAIRQQKS 242
Cdd:smart00310  81 VVAQEIFQLVLEAMQAQKN 99

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648    6 KQGEVFLQHQKHGEKWKRYWLALHPASrhgiarLELSEAIQErstvvVRRHPERKVIRLADCvsVVKLPPHAEACPGENM 85
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGS------LLYYKDDKS-----GKSKEPKGSISLSGC--EVVEVVASDSPKRKFC 69

                          90       100       110
                  ....*....|....*....|....*....|....
gi 528468648   86 aaFCVET----EEKRLVFAAE-RESCGEWVNIIC 114
Cdd:pfam00169  70 --FELRTgertGKRTYLLQAEsEEERKDWIKAIQ 101

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 1, 2, and 3; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain is binds to acidic phospholids and localizes proteins to the plasma membrane. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. In general, PH domains have diverse functions, but are generally involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   6 KQGEVFLQHQKH-GEKWKRYWLALHPASRHGIARLELSEAiQERSTV--VVRRHPERKVIRLADCVSVvkLPPHAEACPG 82
Cdd:cd14676    1 KEGQLYLQQQKFfGKKWRKFWAVLYPASPCGVARLEFFEG-KGGPSGgkPSKRESDRKVIRLSDCVSV--APAGGESSPP 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 528468648  83 ENMAAFCVETEEKRLVFAAERESCGEWVNIICNIAF 118
Cdd:cd14676   78 RDTAAFLLETTEKLYLLAAEAAERADWVQKLCELAF 113

Phosphotyrosine-binding domain (IRS1-like);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   145 SEFKVVVLQSDASVRCGLKGQYWLQ-TGEDMLLIQDLDTRRTVMEWPYKLLRRYGRDKMLFSIEAGRRCESGPGTFNFET 223
Cdd:smart00310   1 KQFWVTIRKTEGLERCPLSGSYRLRlTSEELVLWRGLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQT 80

                           90
                   ....*....|....*....
gi 528468648   224 QQSEEILRLIESAIRQQKS 242
Cdd:smart00310  81 VVAQEIFQLVLEAMQAQKN 99

Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi); The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648 141 REQLSEFKVVVLQS---DASVRCGLkgqywlQTGEDMLLIQDLDTRRT-VMEWPYKLLRRYGRDKMLFSIEAGRRCESGP 216
Cdd:cd13164    1 REQNERFNVFLLPSpnlDVYGECLL------QITHENIYLWDIHNPRVkLVSWPLCSLRRYGRDSTWFTFEAGRMCDTGE 74

                         90       100
                 ....*....|....*....|
gi 528468648 217 GTFNFETQQSEEILRLIESA 236
Cdd:cd13164   75 GLFTFQTREGEQIYQRVHSA 94

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528468648   6 KQGEVFLQHQKHGEKWKRYWLALHPasrhgiARLELSEAIQERSTVvvrrhpERKVIRLADCVSVVKLPPHAEACpgenm 85
Cdd:cd00821    1 KEGYLLKRGGGGLKSWKKRWFVLFE------GVLLYYKSKKDSSYK------PKGSIPLSGILEVEEVSPKERPH----- 63

                         90       100       110
                 ....*....|....*....|....*....|
gi 528468648  86 aAFCVETEEKR-LVFAAE-RESCGEWVNII 113
Cdd:cd00821   64 -CFELVTPDGRtYYLQADsEEERQEWLKAL 92

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528468648  61 VIRLADCVSVVKLPPHAEAcPGEnmaaFCVETEEKRLVFAAERE-SCGEWVNIIcniafQKQ 121
Cdd:cd13215   64 TIDLRYATSIELSKSNGEA-TTS----FKIVTNSRTYKFKADSEtSADEWVKAL-----KKQ 115