Overview of the membrane-associated RING-CH (MARCH) E3 ligase family

•Membrane bound MARCH proteins share a RINGv domain followed by two transmembrane helices.•The transmembrane helices reveal the motif G/AxxxG/A in most membrane bound MARCH proteins.•Most validated substrates of the membrane bound MARCH are themselves membrane bound. E3 ligases are critical checkpoi...

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Bibliographic Details
Published in:New biotechnology 2017-09, Vol.38 (Pt A), p.7-15
Main Authors: Bauer, Johannes, Bakke, Oddmund, Morth, J. Preben
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Animals
GxxxG
Humans
MARCH E3 ligase
MARCH-1
MHC-II
Multigene Family
Phylogeny
Protein Multimerization
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary:•Membrane bound MARCH proteins share a RINGv domain followed by two transmembrane helices.•The transmembrane helices reveal the motif G/AxxxG/A in most membrane bound MARCH proteins.•Most validated substrates of the membrane bound MARCH are themselves membrane bound. E3 ligases are critical checkpoints for protein ubiquitination, a signal that often results in protein sorting and degradation but has also been linked to regulation of transcription and DNA repair. In line with their key role in cellular trafficking and cell-cycle control, malfunction of E3 ligases is often linked to human disease. Thus, they have emerged as prime drug targets. However, the molecular basis of action of membrane-bound E3 ligases is still unknown. Here, we review the current knowledge on the membrane-embedded MARCH E3 ligases (MARCH-1-6,7,8,11) with a focus on how the transmembrane regions can contribute via GxxxG-motifs to the selection and recognition of other membrane proteins as substrates for ubiquitination. Further understanding of the molecular parameters that govern target protein recognition of MARCH E3 ligases will contribute to development of strategies for therapeutic regulation of MARCH-induced ubiquitination.
ISSN:1871-6784
1876-4347
DOI:10.1016/j.nbt.2016.12.002