Function and Biology

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4

Source organism: Homo sapiens
Biochemical function: signal transducer activity
Biological process: cell surface receptor signaling pathway
Cellular component: nucleus

EC 2.3.2.27: RING-type E3 ubiquitin transferase

Reaction catalysed:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)- ubiquitinyl-[acceptor protein]-L-lysine.
Comments:
  • The RING domain of E3 ubiquitin transferase serves as a mediator bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme and the acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin an the epsilon-amino group of an L-lysine residue of the acceptor protein.
  • The RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin (unlike the HECT domain, EC 2.3.2.26).
  • RING-type ubiquitin transferases may occur as single-chain enzymes but also in dimeric forms or in multi-subunit assemblies.
  • Formerly EC 6.3.2.19 and EC 6.3.2.21.
Systematic name:
S-ubiquitinyl-[ubiquitin-conjugating E2 enzyme]-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RING-type)
Alternative Name(s):
  • RING E3 ligase
  • Ubiquitin transferase RING E3

Sequence families

Pfam Protein families (Pfam)
PF02262
Domain description: CBL proto-oncogene N-terminal domain 1
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of Pfam domain PF02262 (CBL proto-oncogene N-terminal domain 1) in E3 ubiquitin-protein ligase CBL in PDB 3bun.

PF02762
Domain description: CBL proto-oncogene N-terminus, SH2-like domain
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of Pfam domain PF02762 (CBL proto-oncogene N-terminus, SH2-like domain) in E3 ubiquitin-protein ligase CBL in PDB 3bun.

PF02761
Domain description: CBL proto-oncogene N-terminus, EF hand-like domain
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of Pfam domain PF02761 (CBL proto-oncogene N-terminus, EF hand-like domain) in E3 ubiquitin-protein ligase CBL in PDB 3bun.

InterPro InterPro annotations
IPR036537
Domain description: Adaptor protein Cbl, N-terminal domain superfamily
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR036860
Domain description: SH2 domain superfamily
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR014742
Domain description: Adaptor protein Cbl, SH2-like domain
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR024162
Domain description: Adaptor protein Cbl
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR024159
Domain description: Adaptor protein Cbl, PTB domain
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR011992
Domain description: EF-hand domain pair
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR014741
Domain description: Adaptor protein Cbl, EF hand-like
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
IPR003153
Domain description: Adaptor protein Cbl, N-terminal helical
Occurring in:
  1. E3 ubiquitin-protein ligase CBL

Structure domains

CATH CATH domains
3.30.505.10
Class: Alpha Beta
Architecture: 2-Layer Sandwich
Topology: SHC Adaptor Protein
Homology: SHC Adaptor Protein
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of CATH domain 3.30.505.10 (SHC Adaptor Protein) in E3 ubiquitin-protein ligase CBL in PDB 3bun.
1.10.238.10
Class: Mainly Alpha
Architecture: Orthogonal Bundle
Topology: Recoverin; domain 1
Homology: EF-hand
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of CATH domain 1.10.238.10 (Recoverin; domain 1) in E3 ubiquitin-protein ligase CBL in PDB 3bun.
1.20.930.20
Class: Mainly Alpha
Architecture: Up-down Bundle
Topology: Transcription Elongation Factor S-II; Chain A
Homology: N-terminal domain of cbl (N-cbl)
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of CATH domain 1.20.930.20 (Transcription Elongation Factor S-II; Chain A) in E3 ubiquitin-protein ligase CBL in PDB 3bun.
SCOP SCOP annotations
47669
Class: All alpha proteins
Fold: N-cbl like
Superfamily: N-terminal domain of cbl (N-cbl)
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of SCOP domain 47669 (N-terminal domain of cbl (N-cbl)) in E3 ubiquitin-protein ligase CBL in PDB 3bun.
55551
Class: Alpha and beta proteins (a+b)
Fold: SH2-like
Superfamily: SH2 domain
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of SCOP domain 55551 (SH2 domain) in E3 ubiquitin-protein ligase CBL in PDB 3bun.
47547
Class: All alpha proteins
Fold: EF Hand-like
Superfamily: EF-hand
Occurring in:
  1. E3 ubiquitin-protein ligase CBL
1 copy of SCOP domain 47547 (EF-hand modules in multidomain proteins) in E3 ubiquitin-protein ligase CBL in PDB 3bun.