LRSAM1

LRSAM1 is a ring finger protein involved in a variety of functions, including regulation of signaling pathways and cell adhesion, mediation of self-ubiquitylation, and involvement in cargo sorting during receptor endocytosis. Mutations in this gene have been associated with Charcot-Marie-Tooth disease. Multiple transcript variants encoding different isoforms have been identified for this gene.

Full Name

leucine rich repeat and sterile alpha motif containing 1

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).

Biological Process

AutophagyIEA:UniProtKB-KW
Negative regulation of endocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of autophagosome assemblyManual Assertion Based On ExperimentIMP:GO_Central
Positive regulation of xenophagyManual Assertion Based On ExperimentIMP:GO_Central
Protein autoubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Protein polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Ubiquitin-dependent endocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Viral buddingManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cytoplasm
Displays a punctuate distribution and localizes to a submembranal ring (PubMed:15256501).
Localizes to intracellular bacterial pathogens (PubMed:23245322).

Involvement in disease

Charcot-Marie-Tooth disease 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.

PTM

Ubiquitination promoted by PHF23 leads to proteasomal degradation.