MARCHF6

Last update 08 May 2025

Basic Info

Synonyms

Doa10 homolog, E3 ubiquitin-protein ligase MARCHF6, KIAA0597

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Introduction

E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (PubMed:15673284). Promotes ubiquitination of DIO2, leading to its degradation (PubMed:19651899). Promotes ubiquitination of SQLE, leading to its degradation (PubMed:24449766). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May cooperate with UBE2G1 (PubMed:15673284).

100 Clinical Results associated with MARCHF6

100 Translational Medicine associated with MARCHF6

0 Patents (Medical) associated with MARCHF6

Literatures (Medical) associated with MARCHF6

01 Nov 2024·Journal of Lipid Research

Development of a monoclonal antibody to study MARCH6, an E3 ligase that regulates proteins that control lipid homeostasis

Article

Author: Kober, Daniel L. ; Donnelly, Linda ; Kober, Daniel L ; Xu, Shimeng ; Radhakrishnan, Arun ; Mak, Myra

Membrane-associated ring-CH-type finger 6 (MARCH6), also designated as TEB4 or RNF176, is an E3 ligase that is embedded in membranes of the endoplasmic reticulum where it ubiquitinates many substrate proteins to consign them to proteasome-mediated degradation. In recent years, MARCH6 has been identified as a key regulator of several metabolic pathways, including cholesterol and lipid droplet homeostasis, protein quality control, ferroptosis, and tumorigenesis. Despite its importance, there are currently no specific antibodies to detect and monitor MARCH6 levels in cultured cells and animals. Here, we address this deficiency by generating a monoclonal antibody that specifically detects MARCH6 in cultured cells of insect, mouse, hamster, and human origin, as well as in mouse tissues, with minimal cross-reactivity against other proteins. We then used this antibody to assess two properties of MARCH6. First, analysis of mouse tissues with this antibody revealed that the liver contained the highest levels of March6. Second, analysis of five different cell lines with this antibody showed that endogenous levels of MARCH6 are unchanged as the cellular content of cholesterol is varied. This reagent promises to be a useful tool in interrogating additional signaling roles of MARCH6.

01 Oct 2024·Zygote

Genomic and transcriptomic evaluations of infertile or subfertile Arunachali yak sperm

Article

Author: Sarkar, Mihir ; Bhati, Jyotika ; Mishra, Dwijesh Chandra ; Kour, Aneet ; Das, Pranab Jyoti

AbstractSperm infertility or subfertility is detrimental to the precious highland germplasm like yak whose population has been gradually declining in India. Understanding the ‘omic’ landscape of infertile or subfertile yak sperm can reveal some interesting insights. In an attempt to do the same, this study considered the semen of infertile or subfertile yak bulls for whole-genome and transcriptome evaluations. DNA sequencing revealed that the yak sperm genome contains the necessary genes to carry out all the important biological processes related to the growth, development, survival and multiplication of an organism. Interestingly, RNA Seq results highlighted that genes like VAMP7, MYLK, ARAP2 and MARCH6 showed increased expression, while biological processes related to immune response (GO:0043308, GO:0002447, GO:0002278, GO:0043307, GO:0043312, GO:0002283, GO:0043299 and GO:0002446) were significantly overrepresented. These findings hint at a possible role played by immune system in regulating infertility or subfertility in yaks. Further, in-depth studies can validate these findings and help in improving our biological understanding in this area.

01 Oct 2024·Journal of Biological Chemistry

Delineation of the substrate recognition domain of MARCHF6 E3 ubiquitin ligase in the Ac/N-degron pathway and its regulatory role in ferroptosis

Article

Author: Hwang, Cheol-Sang ; Yang, Jihye ; Kim, Sang-Yoon

Nα-terminal acetylation in eukaryotic proteins creates specific degradation signals (Ac/N-degrons) targeted for ubiquitin-mediated proteolysis via the Ac/N-degron pathway. Despite the identification of key components of the Ac/N-degron pathway over the past 15 years, the precise recognition domain (Ac/N domain) remains unclear. Here, we defined the Ac/N domain of the endoplasmic reticulum MARCHF6 E3 ubiquitin ligase through a systematic analysis of its cytosol-facing regions using alanine-stretch mutagenesis, chemical crosslinking-based co-immunoprecipitation-immunoblotting, and split-ubiquitin assays in human and yeast cells. The Ac/N domain of MARCHF6 exhibits preferential binding specificity to Nα-terminally acetylated proteins and peptides over their unacetylated counterparts, mediating the degradation of Ac/N-degron-bearing proteins, such as the G-protein regulator RGS2 and the lipid droplet protein PLIN2. Furthermore, abolishing the recognition of Ac/N-degrons by MARCHF6 stabilized RGS2 and PLIN2, thereby increasing the resistance to ferroptosis, an iron-dependent lipid peroxidation-mediated cell death. These findings provide mechanistic and functional insights into how MARCHF6 serves as a rheostatic modulator of ferroptosis by recognizing Ac/N-degron substrates via its Ac/N domain and non-Ac/N-degron substrates via distinct recognition sites.

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MARCHF6

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