LRSAM1
Domain
The coiled coil domains interact with the SB domain of TSG101.
The PTAP motifs mediate the binding to UEV domains.
The LRR domain is necessary and sufficient for localization to bacterial targets.
The RING domain is required for ubiquitination.
Function
E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098).
Involvement in disease
Charcot-Marie-Tooth disease, axonal, 2P
CMT2P
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Ubiquitination promoted by PHF23 leads to proteasomal degradation.
Tissue Specificity
Highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue.
Cellular localization
- Cytoplasm
- Displays a punctuate distribution and localizes to a submembranal ring (PubMed:15256501). Localizes to intracellular bacterial pathogens (PubMed:23245322).
Alternative names
TAL, UNQ6496/PRO21356, LRSAM1, E3 ubiquitin-protein ligase LRSAM1, Leucine-rich repeat and sterile alpha motif-containing protein 1, RING-type E3 ubiquitin transferase LRSAM1, Tsg101-associated ligase, hTAL