E3 ubiquitin-protein ligase NHLRC1; malin; NHL repeat-containing protein 1 (NHLRC1, EPM2B)

Function

• E3 ubiquitin-protein ligase
• in complex with EPM2A/laforin & HSP70 suppresses toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system
• ubiquitinates PPP1R3C/PTG (laforin-dependent), & targets it for proteasome-dependent degradation
  • this degradation decreases glycogen accumulation
• polyubiquitinates EPM2A/laforin & ubiquitinates AGL & targets them for proteasome-dependent degradation
• protein modification; protein ubiquitination
• interacts with AGL
• interacts (via the NHL repeats) with EPM2A/laforin
• forms a complex with EPM2A/laforin & HSP70

Structure

• contains 6 NHL repeats
• contains 1 RING-type Zn+2 finger
  • the RING domain is essential for ubiquitin E3 ligase activity

Compartment

• endoplasmic reticulum
• lesser amounts in nucleus

Expression

• expressed in brain, cerebellum, spinal cord, medulla, heart, liver, skeletal muscle & pancreas

Pathology

• mutations associated with myoclonic epilepsy of Lafora

More general terms

• ring finger protein
• E3 ubiquitin ligase

Additional terms

• progressive myoclonic epilepsy 2A; myoclonic epilepsy of Lafora (MELF)

Database

• OMIM: https://mirror.omim.org/entry/608072
• OMIM: https://mirror.omim.org/entry/254780
• UniProt: http://www.uniprot.org/uniprot/Q6VVB1.html