2BQ0,2C23,2O02,3RDH


Conserved Protein Domain Family
14-3-3_beta_zeta

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cd10022: 14-3-3_beta_zeta 
Click on image for an interactive view with Cn3D
14-3-3 beta and zeta isoforms of 14-3-3 protein
14-3-3 protein beta and zeta isoform (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta and zeta polypeptide) are encoded by the YWHAB gene and YWHAZ gene in humans. They have been linked to mitogenic signaling and the cell cycle machinery, and to cancer initiation and progression, respectively. The beta isoform has been shown to interact with RAF1 and CDC25 phosphatases and its overexpression is associated with invasion, migration, metastasis and proliferation of tumor cells and its elevated levels are correlated with tumor size, the number of lymph node metastases and a reduced survival rate. It is significantly overexpressed in lung cancer tissues, mutated chronic lymphocytic leukemia (M-CLL), gastric cancer tissues, aflatoxin B1-induced rat hepatocellular carcinoma K1 and K2 cells, as well as renal cell carcinoma cysts, and can potentially be used as a diagnostic and prognostic biomarker in the cancer. Numerous proteins involved in anti-apoptosis and tumor progression were also found to be differentially expressed in gastric cancer cells where 14-3-3 beta is overexpressed. 14-3-3 beta also interacts with human Dapper1 (hDpr1), a key negative regulator of Wnt signaling, via hDpr1 phosphorylation by protein kinase A, thus attenuating the ability of hDpr1 to promote Dishevelled (Dvl) degradation, and subsequently enhancing Wnt signaling. The zeta isoform is ubiquitously expressed and localized to most subcellular regions, including the cytoplasm, plasma membrane, mitochondria, and nucleus. Its overexpression and gene amplification in multiple cancers are correlated with poor prognosis and chemoresistance in cancer patients. 14-3-3 zeta has been identified as a biomarker with high sensitivity and specificity for diagnosis and prognosis in multiple tumor types, including hepatocellular carcinoma, head and neck cancer, indicating a potential clinical application for using 14-3-3 zeta in selecting treatment options and predicting cancer outcome. It also interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells.
Statistics
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PSSM-Id: 206758
Aligned: 9 rows
Threshold Bit Score: 464.541
Created: 12-Jul-2010
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
dimer interfacepeptide binding
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:dimer interface [polypeptide binding site]
Evidence:
  • Structure:2O02: Human 14-3-3 protein zeta isoform homodimer; contacts at 4.0A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1           #  ##  ## ## #  #                                    #  #   #         #  ##  
2BQ0_A         4 DKSELVQKAKLAEQAERYDDMAAAMKAVTEQGhELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTERNEKKQQMGKE 83  human
Q8AVQ3         2 DKSELVQKAKLSEQAERYDDMAASMKAVTELGaELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTEGNDKRQQMARE 81  African clawed ...
Q5PRD0         2 DKSDLVQKAKLAEQAERYDDMAASMKAVTEGGvELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTEGNEKKQQMARE 81  zebrafish
2C23_A         4 DKSELVQKAKLAEQAERYDDMAAAMKAVTEQGhELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTERNEKKQQMGKE 83  human
2O02_A         2 DKNELVQKAKLAEQAERYDDMAACMKSVTEQGaELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMARE 81  human
Q5ZKC9         2 DKNELVQKAKLAEQAERYDDMASCMKSVTEQGaELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMARE 81  chicken
NP_001080117   2 DKNELVQKAKLAEQAERYDDMAACMKRVTEEGgELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQEMSRE 81  African clawed ...
3RDH_A         5 DKNELVQKAKLAEQAERYDDMAACMKSVTEQGaELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMARE 84  human
XP_003219507   2 DKNELVQKAKLAEQAERYDDMAACMKSVTEQGaELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMARE 81  green anole
Feature 1        #  ##  #                                                                        
2BQ0_A        84 YREKIEAELQDICNDVLELLDKYLIPNATQPESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISKKEMQ 163 human
Q8AVQ3        82 YREKVETELQDICKDVLDLLDRFLVPNATPPESKVFYLKMKGDYYRYLSEVASGDSKQETVANSQQAYQEAFEISKSEMQ 161 African clawed ...
Q5PRD0        82 YREKIEAELQEICNDVLGLLEKYLIPNASQAESKVFYLKMKGDYYRYLSEVASGDSKRTTVENSQKAYQDAFEISKKEMQ 161 zebrafish
2C23_A        84 YREKIEAELQDICNDVLELLDKYLIPNATQPESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISKKEMQ 163 human
2O02_A        82 YREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQ 161 human
Q5ZKC9        82 YREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVEQSQQAYQEAFEISKKEMQ 161 chicken
NP_001080117  82 YREKIEAELREICNDVLNLLDKFLIANATQPESKVFYLKMKGDYYRYLAEVAAGDAKSDIVGQSQKAYQDAFDISKTEMQ 161 African clawed ...
3RDH_A        85 YREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQ 164 human
XP_003219507  82 YREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVEQSQQAYQEAFEISKKEMQ 161 green anole
Feature 1                                                                             
2BQ0_A       164 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTS 232 human
Q8AVQ3       162 PTHPIRLGLALNFSVFYYEIlNSPDKACSLAKSAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTS 230 African clawed frog
Q5PRD0       162 PTHPIRLGLALNFSVFYYEIlNTPEQACSLAKTAFDEAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTS 230 zebrafish
2C23_A       164 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTS 232 human
2O02_A       162 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTS 230 human
Q5ZKC9       162 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTS 230 chicken
NP_001080117 162 PTHPIRLGLALNFSVFYYEIlNCPDKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTS 230 African clawed frog
3RDH_A       165 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTS 233 human
XP_003219507 162 PTHPIRLGLALNFSVFYYEIlNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTS 230 green anole

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