Conserved Protein Domain Family
mRING-CH-C4HC2H_ZNRF1

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cd16694: mRING-CH-C4HC2H_ZNRF1 
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) and similar proteins
ZNRF1, also known as Nerve injury-induced gene 283 protein (nin283), or peripheral nerve injury protein (PNIP), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is associated with synaptic vesicle membranes. It is N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts, suggesting it may participate in ubiquitin-mediated protein modification. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. ZNRF1 regulates Schwann cell differentiation by proteasomal degradation of glutamine synthetase (GS). It also mediates regulation of neuritogenesis via interaction with beta-tubulin type 2 (Tubb2). Moreover, ZNRF1 promotes Wallerian degeneration by degrading AKT to induce glycogen synthase kinase-3beta (GSK3B)-dependent CRMP2 phosphorylation. Furthermore, ZNRF1 and its sister protein ZNRF2 regulate the ubiquitous Na+/K+ pump (Na+/K+ATPase). In addition, ZNRF1 may be associated with leukemogenesis of acute lymphoblastic leukemia (ALL) with paired box domain gene 5 (PAX5) alteration.
Statistics
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PSSM-Id: 319608
View PSSM: cd16694
Aligned: 8 rows
Threshold Bit Score: 91.1863
Threshold Setting Gi: 501295514
Created: 23-Mar-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
modified
Feature 1: modified RING-CH finger (C4HC2H-type) [structural motif], 8 residue positions
Conserved feature residue pattern:C C C C H C C HClick to see conserved feature residue pattern help
Evidence:
  • Comment:consensus of the canonical C3H2C3-type RING-H2 finger: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, 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.
  • Comment:The RING-CH fingers found in ZNRF proteins are modified as C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger.
  • Comment:putative Zn2+ binding sites

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
Feature 1          #  #              # #  #  #          #  #   
gi 126253846 182 GECVICLEELlQGDTIARLPCLCIYHKSCIDSWFEvNRSCPEHPAD 227
gi 82198478  150 GECVICLEELsQGDTIARLPCLCIYHKSCIDSWFEvNRCCPEHPSD 195
gi 291242618 159 GECVICLDDLqQGDTIARLPCLCIYHKSCIDSWFEvNRSCPEHPND 204
gi 82202400  170 GECVICLEELqQGDTIARLPCLCIYHKSCIDSWFEiNRSCPEHPSD 215
gi 483525392  40 GECVICLEELlQGDTIARLPCLCIYHKSCIDSWFEvNRSCPEHPSD 85
gi 632978235 108 GECVICLEELlQGDTIARLPCLCIYHKSCIDSWFEvNRSCPEHPSD 153
gi 390362897 192 GECVICLEDMlQGDTIARLPCLCIYHKSCIDSWFErNRSCPEHPND 237
gi 501295514  59 GECVICLEELaQGDTIARLPCLCIYHKSCIDRWFEvNRSCPEHPGD 104

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