4GNK,4QJ3,3OHM


Conserved Protein Domain Family
EFh_PI-PLCbeta3

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cd16210: EFh_PI-PLCbeta3 
Click on image for an interactive view with Cn3D
EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3)
PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (PLC-beta3), is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.
Statistics
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PSSM-Id: 320040
View PSSM: cd16210
Aligned: 6 rows
Threshold Bit Score: 295.289
Threshold Setting Gi: 82097392
Created: 18-Nov-2014
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:polypeptide substrate binding site [polypeptide binding site]
Evidence:
  • Structure:4GNK; Homo sapiens PLC-beta3 in complex with G protein alpha q subunit, contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4GNK_B        155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKkrvETALESCGLKFNRSESIRPDEFSLEIFERFlnklclrpDIDKILLEI 234
4QJ3_B        155 RKAYTKLKLQVNQDGRIPVKNILKMFSADKkrvETALESCGLKFNRSESIRPDEFSLEIFERFlnklclrpDIDKILLEI 234
gi 147900969  154 QKAYTKLKLQVNQDGRIPVKNILKMFAADKkrvETALESCGLNFNRGDSIKPEEFTLDIFERFlnklclrpDIDKILLEL 233
gi 637368778  155 QKAYTRLKIQVNQDGRIPVKNILKMFSADKkrvETALESCGLNFNRSESIKPDEFTLEIFERFlnklclrpDIDKILLEI 234
3OHM_B        153 RKAYTKLKLQVNQDGRIPVKNILKMFSADKkrvETALESCGLKFNRSESIRPDEFSLEIFERFlnklclrpDIDKILLEI 232
gi 82097392   128 LKAYTKLKLQVTQDGKIPVKNILKMFSDKKr-vEMALEHCGLIFNRVDGIKPDDFTWEMFQNFlnklsprpEVERIFVDL 206
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
Feature 1                                #######                                         
4GNK_B        235 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPplrpsQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
4QJ3_B        235 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPplrpsQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 305
gi 147900969  234 GAKGKPYLTLEQLMDFLNQKQRDPRLNEILFPplkrdQVRQLIEKYEPNRQFLDRDQMSMEGFSRFLGGHE 304
gi 637368778  235 GAKGKPYLSLDQLMDFINQKQRDPRLNEVLYPpltqaQVRQLIDKYEPNQQFQQRDQMSMEGFGRYLGGEE 305
3OHM_B        233 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPplrpsQARLLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 303
gi 82097392   207 GSKGKPFLSLDQLMDFINRKQRDSRLNEVLYPplkrdQVRQLMEKYETNTSQLERDQISLMSFTKYLGGEE 277

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