2L0B


Conserved Protein Domain Family
RING-H2_PJA1_2

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cd16465: RING-H2_PJA1_2 
Click on image for an interactive view with Cn3D
RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins
This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.
Statistics
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PSSM-Id: 438128
Aligned: 12 rows
Threshold Bit Score: 83.2723
Created: 2-May-2013
Updated: 17-Oct-2022
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding site
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1: Zn binding site [ion binding site], 8 residue positions
Conserved feature residue pattern:C C C H H C C CClick to see conserved feature residue pattern help
Evidence:
  • Structure:2L0B; Homo sapiens Praja-1 binds two Zn2+ ions through its RING-H2 finger.
  • Comment:C3H2C3-type RING-H2 finger consensus motif: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, where X is any amino acid and the number of X residues varies in different fingers
  • Comment:A RING finger typically binds two zinc atoms, with its Cys and/or His side chains in a unique "cross-brace" arrangement.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1          #  #              # #  #  #          #  #    
2L0B_A         42 CCPICCSEYvkGDVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 87   human
NP_001084595  604 CCAICCSEYikDEILTELPCHHLFHKPCVTLWLQKSGTCPVCRHVL 649  African clawed frog
O43164        633 CCPICCSEYikDDIATELPCHHFFHKPCVSIWLQKSGTCPVCRRHF 678  human
Q8NG27        594 CCPICCSEYvkGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 639  human
XP_007891348  638 SCAICCSEYvkEELVTELPCHHLFHGPCVTLWLQKSGTCPVCRHVL 683  elephant shark
XP_006818510  550 SCAICQCEYkiDDTVNKLPCDHLFHPICINAWLQKSGTCPVCRHVL 595  Saccoglossus kowalevskii
XP_009064252 1041 SCPICLCPCqlEETLTILCCQHLFHPLCIQAWLAKSGTCPVCRCTI 1086 owl limpet
ELU18917      564 TCPICLCSFeiSEEAKILPCQHHFHTLCIQAWLKKSGTCPVCRHVL 609  Capitella teleta
KFQ03661      620 RCTICCSEYvkDEIITELPCHHLFHKTCITLWLQKSGTCPICRHVL 665  white-tailed eagle
AAI25887      606 CCAICCCEYvkDEIATLLPCRHMFHKLCVTLWLRKSGTCPVCRHVL 651  zebrafish
XP_013416023  853 QCPICLNNYncREKASQLPCLHIFHPLCIQAWLIKSGTCPVCRHVL 898  Lingula anatina
XP_006014053  622 CCAICCSEYmkDEIVTELPCHHLFHKPCVTLWLQKSGTCPVCRHVL 667  coelacanth

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