CDD Conserved Protein Domain Family: PH_DOK4_DOK5

cd14678: PH_DOK4_DOK5_DOK6

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

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). 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.

AAL74195 9 VKQGYVKMksrkLGIYRRCWLVFRKsssKGPQRLEKYPDEKSVCLrgcpKVTEISNVKCVTRLPkeakrqAVAIIFTDds 88 human XP_417502 9 VKQGYVRIrsrrLGIYQRCWLVFKKassKGPKRLEKFSDERAAYFrcyhKVTELNNVKNISRMPkstkkhAVGIYFNDdt 88 chicken XP_697365 9 VKQGYVRMrsrkLGIYRRCWLVFKKsssKGPRRLEKYPDEKSAYIracpKVTEISNVKNVTRLPrdtkrqAVAIVFTDdt 88 zebrafish NP_001080630 9 VRQGYVRMksrkLGIYRRCWLVLRKsssKGPWRLEKYPDERSVLLkaspKVTEISNVKCIMRLPketkrqAVAIIFCDdl 88 African clawed ... NP_001082908 9 VKQGYVRIrskkLGIFRRCWLVFKKassKGPRRLEKYPDEKAAYFrsfhKITELHNIKNITRMPretkkhAVAIIFCDet 88 zebrafish XP_419111 9 VKQGYVKIrsrkLGIFRRCWLVFKKassKGPRRLEKFPDEKAAYFrnfhKVTELHNIKNITRLPretkkhAVAIIFHDet 88 chicken XP_002935431 9 VKQGYVKIrsrrLGIYQRCWLVFKKassKGPKRLEKFSDERAAYFrcyhKVTELNNVKNILRLPkttkkhALGIFFTDdt 88 western clawed ... XP_003641936 88 FCRGGGRVaplcPQIYRRCWLVFRKsssKGPQRLEKYPDEKAACLrgcpKVTEISNVKCITRLPketkrqAVAIVFADds 167 chicken NP_001134973 9 VKQGYVYFrskhLWIYRRCWLVLRRdssKGPKRLERFSNEQAANCqchhKVTDLRKIRSVARPPrdkkkhAVVLTFKDds 88 Atlantic salmon XP_002407926 35 PCQGPLSLsggtSQVWQRRWLVLRRaagRTPCRLEKYLEERHARLhagqKVVLLGPAASVCRLPasvkrhAFALAFQDgs 114 black-legged tick

AAL74195 89 ARTFTCDSELEAEEWYKTLSVECLG 113 human XP_417502 89 SKTFACESELEADEWCKVLQMECLG 113 chicken XP_697365 89 SRTFTCESELEAEEWFKTLSIECLG 113 zebrafish NP_001080630 89 ARTFTCDSELEAEEWYKVLSMECPG 113 African clawed frog NP_001082908 89 SKTFACESELEAEEWWKLLCLECLG 113 zebrafish XP_419111 89 SKTFACESELEAEEWCKHLCMECLG 113 chicken XP_002935431 89 SKTFACESELEADEWCKVLHTECLG 113 western clawed frog XP_003641936 168 ARTFTCDSELEAEEWYKALSVECLG 192 chicken NP_001134973 89 PKAFACDSELDAKEWCKVLQMECLE 113 Atlantic salmon XP_002407926 115 VKAIACDSDLEADTWVKLMVQECLE 139 black-legged tick

Conserved Protein Domain FamilyPH_DOK4_DOK5_DOK6

Conserved Protein Domain Family
PH_DOK4_DOK5_DOK6