Conserved Protein Domain Family
RING-HC_Cbl-c
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cd16710: RING-HC_Cbl-c 
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins
Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).
Links
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Statistics
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PSSM-Id: 438370
Aligned: 3 rows
Threshold Bit Score: 142.916
Created: 19-Mar-2015
Updated: 17-Oct-2022
Structure
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Aligned Rows:
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Zn binding site
Feature 1: Zn binding site [ion binding site], 8 residue positions
Conserved feature residue pattern:C C C H C C C CClick to see conserved feature residue pattern help
Evidence:
  • Comment:based on the structure of human Cbl with bound Zn2+ ions through its RING-HC finger.
  • Comment:C3HC4-type RING-HC finger consensus motif: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-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.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                    #  #           # #  #  #           #  #           
Q9ULV8    336 EQLQLYWAMDSTFELCKICAESNKDVKIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEIKGWEAVS 400 human
G3V8H4    336 EQLQLYQAMNSTFELCKICTERDKDVRIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEIKGREAVS 400 Norway rat
Q80XL1    335 EQLLLYQAMNSTFQLCKICAERDKDVRIEPCGHLLCSCCLAAWQDSDSQTCPFCRCEIKGREAVS 399 house mouse

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