Affinage

MARCHF1

E3 ubiquitin-protein ligase MARCHF1 · UniProt Q8TCQ1

Length
289 aa
Mass
32.3 kDa
Annotated
2026-04-28
72 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MARCHF1 is a membrane-associated RING-CH E3 ubiquitin ligase that serves as a master regulator of surface receptor turnover in antigen-presenting cells, controlling adaptive immune priming, T helper cell polarization, and thymic regulatory T cell generation. In resting dendritic cells, B cells, and monocytes, MARCHF1 constitutively ubiquitinates the MHC class II β-chain and CD86 costimulatory molecule, driving their endocytosis and lysosomal degradation; upon APC activation or maturation, MARCHF1 expression is rapidly extinguished at both transcriptional and post-translational levels (the protein has a half-life under 30 minutes and is expressed at ~500 molecules per DC), thereby stabilizing surface pMHC-II–CD86 complexes for productive CD4 T cell stimulation (PMID:18305173, PMID:19880452, PMID:40397676). Unbiased plasma membrane proteomics confirms MHC-II and CD86 as the primary physiological substrates in hematopoietic APCs, and MARCHF1-dependent MHC-II ubiquitination maintains lipid raft and tetraspanin web homeostasis essential for Treg generation and TH2 polarization (PMID:35492398, PMID:29371232, PMID:34652961). Beyond immune regulation, MARCHF1 ubiquitinates the insulin receptor to modulate hepatic insulin sensitivity, promotes ferroptosis by targeting GPX4 for degradation, regulates TBK1 via K63-linked ubiquitination to attenuate mTOR signaling, and restricts replication of influenza A virus and HIV by limiting viral glycoprotein availability (PMID:27577745, PMID:37802009, PMID:39061024, PMID:36423158, PMID:37773002).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2008 High

    The identity of the E3 ligase responsible for MHC-II turnover in resting DCs was unknown; two independent studies established that MARCHF1 ubiquitinates MHC-II β-chain to drive its internalization, and that IL-10 induces MARCHF1 to downregulate MHC-II in monocytes, defining MARCHF1 as the key MHC-II ubiquitin ligase in professional APCs.

    Evidence Co-immunoprecipitation, ubiquitination assays, and siRNA knockdown in primary human DCs and monocytes

    PMID:18305173 PMID:18389477

    Open questions at the time
    • Structural basis of MARCHF1–MHC-II interaction not defined
    • E2 enzyme(s) partnering with MARCHF1 for MHC-II ubiquitination not identified
  2. 2009 High

    Whether MARCHF1-mediated MHC-II ubiquitination was physiologically required in vivo was untested; MARCH-I knockout and MHC-II ubiquitination-site knockin mice demonstrated that MARCHF1-dependent MHC-II ubiquitination is essential for steady-state cDC function, while structure-function analysis revealed the protein's extremely short half-life and lysosomal degradation.

    Evidence MARCH-I KO mice, MHC-II ubiquitin-acceptor KI mice, antigen presentation assays, lysosomal inhibitor studies, domain mutagenesis

    PMID:19880452 PMID:19917682

    Open questions at the time
    • Mechanism of activation-induced MARCHF1 transcriptional silencing not resolved
    • Contribution of individual cytoplasmic tail domains to in vivo function unclear
  3. 2011 High

    How surface MHC-II is protected from MARCHF1 during DC maturation was unknown; CD83's transmembrane domain was shown to block MARCHF1–MHC-II association, providing a mechanistic counterbalance to MARCHF1 activity.

    Evidence ENU mutagenesis eliminating CD83 TM domain, genetic complementation, T cell functional assays in mice

    PMID:21220452

    Open questions at the time
    • Direct CD83 TM–MARCHF1 TM interaction interface not structurally resolved
    • Whether CD83 also protects CD86 from MARCHF1 independently of MHC-II not tested
  4. 2012 Medium

    MARCHF1 self-regulation was poorly understood; autoubiquitination via K48-linked chains, homodimerization, and trans-ubiquitination of inactive partners were demonstrated, along with identification of cytoplasmic sorting motifs directing MARCHF1 trafficking including exosome incorporation.

    Evidence FRET, Co-IP with chain-specific antibodies, half-life measurements, site-directed mutagenesis and exosome isolation

    PMID:22508929 PMID:23264739

    Open questions at the time
    • Physiological role of MARCHF1 in exosomes not established
    • Whether homodimerization is required for substrate ubiquitination unknown
  5. 2013 High

    The immunological consequence of MARCHF1-mediated MHC-II ubiquitination for T cell tolerance was unknown; MARCHF1-dependent MHC-II ubiquitination proved essential for thymic regulatory T cell generation, and Tollip was identified as a competitive antagonist of MARCHF1 binding to MHC-II.

    Evidence MARCH1 KO and MHC-II ubiquitination mutant mice with in vivo Treg assays; Tollip knockdown and Co-IP in CIITA+ HeLa cells

    PMID:23712430 PMID:24600555

    Open questions at the time
    • Mechanism by which Tollip reduces MARCHF1 protein levels not clarified
    • Whether Tollip–MARCHF1 competition occurs in primary DCs in vivo not confirmed
  6. 2015 High

    How MARCHF1 controls the fate of internalized pMHC-II was unclear; MARCHF1-dependent ubiquitination was shown to redirect internalized pMHC-II from recycling to lysosomal degradation, and IL-10-induced MARCHF1 expression was found to be cell-type specific—operating in macrophages but not DCs.

    Evidence MHC-II ubiquitination mutant mice, biochemical recycling/lysosomal targeting assays, MARCH-I KO macrophages and DCs with antigen presentation readouts

    PMID:26240324 PMID:26408197

    Open questions at the time
    • Sorting adaptors linking ubiquitinated MHC-II to lysosomal targeting not identified
    • Whether other cytokines besides IL-10 regulate MARCHF1 in macrophages not systematically examined
  7. 2016 High

    MARCHF1 substrate range beyond immune molecules was unexplored; an RNAi screen and mouse models revealed that MARCHF1 ubiquitinates the insulin receptor to control surface INSR levels and hepatic insulin sensitivity, establishing a metabolic role.

    Evidence Large-scale RNAi screen, March1 KO and overexpression mice, INSR ubiquitination and insulin signaling assays

    PMID:27577745

    Open questions at the time
    • Whether MARCHF1-INSR interaction occurs in tissues other than liver not tested
    • MARCHF1 recognition determinants on the INSR not mapped
  8. 2018 High

    Multiple mechanistic facets were clarified: MARCHF1 itself undergoes lysine-independent ubiquitination via Ube2D1; MARCHF1-dependent MHC-II ubiquitination indirectly modulates MHC-I surface expression; MARCHF1 controls lipid raft and tetraspanin web homeostasis; and an APC-specific promoter with activation-responsive elements was defined.

    Evidence Ube2D1 knockdown and lysine-less MARCHF1 mutants; MARCH1/MHC-II double-KO epistasis; lipid raft fractionation in KO/KI mice; promoter-GFP reporter truncation assays

    PMID:29371232 PMID:29378848 PMID:29414787 PMID:30001419

    Open questions at the time
    • The E3 ligase mediating MARCHF1's own lysine-independent ubiquitination not identified
    • Structural basis for MHC-II ubiquitination effects on lipid rafts not elucidated
  9. 2020 Medium

    Whether MARCHF1 functions beyond antigen presentation in innate immunity was unknown; MARCHF1 was shown to modulate MAVS/STING/TRIF-induced type I interferon production, and MARCHF1-deficient DCs exhibited intrinsic transcriptional and functional defects despite high surface pMHC-II.

    Evidence March1 KO mice with Plasmodium infection, IFN-I signaling assays; MHC-II ubiquitination-mutant DCs with scRNA-seq and T cell stimulation

    PMID:32606244 PMID:33318291

    Open questions at the time
    • Direct substrates mediating MARCHF1's effect on IFN-I signaling not identified at this stage
    • Causal link between altered DC transcriptome and poor T cell stimulation not resolved
  10. 2021 High

    Multiple advances defined substrate specificity and physiological impact: deep mutational scanning revealed that MARCHF1 recognizes CD86 via a proline-centered hydrophobic surface in its transmembrane domain; unbiased proteomics confirmed MHC-II and CD86 as primary in vivo substrates restricted to hematopoietic APCs; MARCHF1-dependent ubiquitination of both substrates was required for TH2 polarization by lymph node DCs; and HDAC11 was identified as a substrate linking MARCHF1 to OX40L de-repression in allergic DCs.

    Evidence Deep mutational scanning of CD86 TM; plasma membrane proteomics from MARCH1/MARCH8 KO mice; MHC-II/CD86 ubiquitin-acceptor mutant mice with TH2 assays; HDAC11 Co-IP and promoter assays in asthmatic DCs

    PMID:34157285 PMID:34385821 PMID:34652961 PMID:35492398

    Open questions at the time
    • Whether MARCHF1 TM domain directly contacts CD86 TM domain awaits structural confirmation
    • HDAC11 as MARCHF1 substrate reported by single lab only
  11. 2022 Medium

    MARCHF1's antiviral functions were expanded: isoform-specific restriction of influenza A virus was mapped to N-terminal cytoplasmic residues, and MARCHF1 was found to ubiquitinate the transferrin receptor during HCMV infection to regulate iron homeostasis and viral replication.

    Evidence Doxycycline-inducible isoform expression with IAV titer assays; TfR expression/iron assays during HCMV infection with MARCHF1 knockdown

    PMID:35045264 PMID:36423158

    Open questions at the time
    • Direct ubiquitination of TfR by MARCHF1 not shown with purified components
    • Whether IAV restriction involves a defined MARCHF1 substrate unclear
  12. 2023 Medium

    MARCHF1 was established as an E3 ligase for GPX4, linking it to ferroptosis regulation, and was shown to restrict HIV infectivity in macrophages by limiting envelope glycoprotein incorporation into virions—a restriction counteracted by HIV Vpu via miR-25/93-mediated MARCHF1 downregulation.

    Evidence GPX4 ubiquitination assays and ferroptosis readouts in HUVECs; miRNA induction assays, MARCHF1 mRNA knockdown, viral infectivity assays in macrophages

    PMID:37773002 PMID:37802009

    Open questions at the time
    • GPX4 as direct MARCHF1 substrate confirmed in a single lab
    • Whether MARCHF1 restricts HIV by ubiquitinating envelope glycoproteins directly not demonstrated
  13. 2024 Medium

    MARCHF1's substrate repertoire expanded to signaling and metabolic regulators: K63-linked ubiquitination of TBK1 attenuates mTOR signaling; ubiquitination-dependent degradation of PCSK9 in neurons protects against ischemic brain injury; MARCHF1 interaction with GABAB receptors under ischemia blocks receptor recycling; and MARCHF1 retains Ebola virus GP at the trans-Golgi via furin interaction.

    Evidence Co-IP and ubiquitination assays for TBK1, PCSK9, and GABAB receptors; MCAO/R mouse model; interfering peptide rescue; EBOV-pseudovirus infectivity and furin Co-IP

    PMID:38299743 PMID:39061024 PMID:39115562 PMID:39779794

    Open questions at the time
    • Each new substrate reported by a single laboratory; independent replication needed
    • Whether TBK1 K63-ubiquitination by MARCHF1 requires a specific E2 enzyme unknown
    • Physiological relevance of MARCHF1-GABAB interaction outside ischemia not addressed
  14. 2025 High

    Endogenous MARCHF1 protein was quantified for the first time (~500 molecules/DC) using a V5 knock-in, confirming CD83 as an endogenous antagonist; additional cancer-relevant substrates PHLPP2, REST, and MYCT1 were identified, and SARS-CoV-2 M protein was shown to hijack MARCHF1-dependent GPX4 degradation to induce ferroptosis.

    Evidence V5 epitope knock-in to endogenous locus with quantitative flow cytometry; Co-IP/ubiquitination assays and in vivo tumor models for PHLPP2/REST/MYCT1; M protein–GPX4 interaction mapping with MARCHF1-dependent ubiquitination assays

    PMID:35122633 PMID:39428668 PMID:40186530 PMID:40397676 PMID:40533483

    Open questions at the time
    • Cancer-related substrates each reported by single labs; validation in independent systems pending
    • Structural basis for MARCHF1 substrate selectivity across diverse transmembrane and soluble proteins remains unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of MARCHF1 exists, and the mechanism by which a single RING-CH E3 ligase recognizes such a diverse set of transmembrane and cytoplasmic substrates (MHC-II, CD86, INSR, GPX4, TBK1, TfR, PCSK9, GABAB receptor, PHLPP2, REST, MYCT1, HDAC11) remains unresolved. The E3 ligase that mediates MARCHF1's own lysine-independent ubiquitination has not been identified.
  • No crystal or cryo-EM structure of MARCHF1 or any MARCHF1–substrate complex
  • E3 ligase targeting MARCHF1 for degradation not identified
  • Systematic comparison of MARCHF1 vs MARCH8 substrate selectivity determinants lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 20 GO:0016874 ligase activity 6
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 3 GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 12 R-HSA-392499 Metabolism of proteins 10 R-HSA-162582 Signal Transduction 4 R-HSA-9609507 Protein localization 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CD83CD86GPX4HLA-DRB1INSRPCSK9TBK1TFRC

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MARCH1 (RING-CH ubiquitin E3 ligase) promotes ubiquitination of the HLA-DR beta-chain, inducing surface internalization of mature HLA-DR complexes in non-activated human monocyte-derived dendritic cells, thereby reducing their stability and surface levels. Maturation-dependent down-regulation of MARCH1 is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, flow cytometry in primary human DCs Proceedings of the National Academy of Sciences of the United States of America High 18305173
2008 IL-10 strongly induces MARCH1 mRNA expression in human primary monocytes, leading to mono- and poly-ubiquitination of MHC class II molecules and their intracellular sequestration. Direct interaction between MHC-II and MARCH1 was demonstrated, and siRNA-mediated knockdown of MARCH1 reverses IL-10-induced MHC-II down-regulation. Co-immunoprecipitation, siRNA knockdown, ubiquitination assays, flow cytometry in primary human monocytes European journal of immunology High 18389477
2009 MARCH1 expression is regulated at the posttranscriptional level with a half-life <30 min. Degradation occurs partly in lysosomes via cysteine proteases. Discrete domains in the N- and C-terminal cytoplasmic tails are required for destabilization, proper localization, and functional interaction with substrates (MHC-II and CD86). Mutational analysis, lysosomal inhibitor treatment, half-life measurements, reporter fusion assays in primary DCs and APC cell lines Journal of immunology (Baltimore, Md. : 1950) High 19880452
2009 MARCH-I-mediated MHC II ubiquitination is necessary for maintenance of conventional dendritic cell (cDC) functions in steady state. MARCH-I-deficient cDCs accumulate MHC-II and B7-2 but exhibit impaired antigen-presenting ability. MHC-II knockin mice whose MHC-II cannot be ubiquitinated show cDC dysfunction similar to MARCH-I KO mice, establishing that MHC-II (not B7-2) ubiquitination drives this effect. MARCH-I knockout mice, MHC-II ubiquitination knockin mice, in vivo antigen presentation assays, cytokine production assays Journal of immunology (Baltimore, Md. : 1950) High 19917682
2011 The transmembrane domain of CD83 blocks MHC class II association with MARCH1, thereby opposing MARCH1-dependent ubiquitination and degradation of MHC class II and CD86 in dendritic cells. IL-10-driven, MARCH1-dependent ubiquitination and degradation is antagonized by the CD83 TM domain. ENU-induced mutagenesis eliminating CD83 TM domain, genetic complementation, flow cytometry, functional T cell assays in mice The Journal of experimental medicine High 21220452
2012 MARCH1 undergoes autoubiquitination via K48-linked polyubiquitin chains and regulates its own expression. MARCH1 homodimerizes and forms heterodimers with other MARCH family members. An inactive MARCH1 mutant (M1WI) has prolonged half-life; coexpression of active MARCH1 decreases M1WI levels, suggesting transubiquitination. Immunoprecipitation with polyubiquitin chain-specific antibodies, FRET energy transfer, co-immunoprecipitation, half-life measurements in transfected human cell lines Journal of immunology (Baltimore, Md. : 1950) Medium 22508929
2012 MARCH1 cytoplasmic N-terminal tail contains endosomal sorting motifs. The C-terminal domain contains intracellular sorting signals and a functional 221VQNC224 motif that affects spatial organization of cytoplasmic regions and influences MARCH1 trafficking. Mutation of C-terminal tyrosine-based sorting signals reduces incorporation of MARCH1 into exosomes. Site-directed mutagenesis, reporter molecule fusions, subcellular localization assays, exosome isolation, structure-function analysis Journal of cell science Medium 23264739
2013 MARCH1-mediated MHC-II ubiquitination in dendritic cells is required for proper production of naturally occurring regulatory T cells (Treg) in the thymus. DCs deficient in MARCH1 or lacking MHC-II ubiquitination fail to generate antigen-specific Treg cells in vivo and in vitro. MARCH1 KO mice, MHC-II ubiquitination mutant mice, in vivo and in vitro Treg generation assays, antigen presentation assays The Journal of experimental medicine High 23712430
2013 Tollip competes with MARCH1 for binding to MHC-II molecules and strongly reduces MARCH1 protein levels, thereby antagonizing MARCH1-dependent MHC-II downregulation. Knockdown of Tollip increases HLA-DR expression; truncation of HLA-DR cytoplasmic tails abrogates the effect of Tollip. Tollip knockdown, MARCH1 co-expression, co-immunoprecipitation, flow cytometry in CIITA+ HeLa cells Results in immunology Medium 24600555
2015 March-I ubiquitination of pMHC-II promotes degradation of newly synthesized pMHC-II in dendritic cells and prevents recycling of internalized pMHC-II from the cell surface back to the plasma membrane, instead targeting it to lysosomes. Acute APC activation terminates March-I expression, enabling efficient pMHC-II recycling and preventing lysosomal targeting. MHC-II ubiquitination mutant mice, biochemical recycling assays, lysosomal targeting assays, functional antigen presentation assays in DCs and B cells Proceedings of the National Academy of Sciences of the United States of America High 26240324
2015 IL-10 stimulates expression of March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in dendritic cells and does not suppress MHC-II or CD86 on DCs, establishing a cell-type-specific mechanism of IL-10-mediated immunosuppression. MARCH-I KO macrophages and DCs, flow cytometry, antigen presentation assays, IL-10 stimulation in primary cells The Journal of biological chemistry High 26408197
2016 MARCH1 impairs cellular insulin action by ubiquitinating the insulin receptor (INSR) to decrease cell surface INSR levels in the basal state (before insulin stimulation). March1 loss-of-function enhances, and March1 overexpression impairs, hepatic insulin sensitivity in mice. Large-scale RNAi screen, March1 KO mice, March1 overexpression mouse model, INSR ubiquitination assays, insulin signaling assays Nature communications High 27577745
2018 March-I is ubiquitinated on non-lysine residues (lysine-independent ubiquitination) by an unidentified E3 ligase together with the ubiquitin-conjugating enzyme Ube2D1. March-I E3 ligase activity is not required for its own ubiquitination. Knockdown of Ube2D1 impairs March-I ubiquitination and increases March-I expression, enhancing March-I-dependent MHC-II downregulation. Lysine-less March-I variant expression, Ube2D1 knockdown, ubiquitination assays, western blot in transfected cells The Journal of biological chemistry Medium 29414787
2018 MARCH1-mediated ubiquitination of MHC-II indirectly regulates MHC-I surface expression in B cells and dendritic cells. Absence of MARCH1 reduces surface MHC-I expression not by direct MARCH1 ubiquitination of MHC-I but through altered MHC-II trafficking, establishing an intersection between MHC-I and MHC-II pathways. MARCH1 KO mice, MHC-II KO in March1-/- cells, MHC-II ubiquitination mutant replacement, flow cytometry, CD8 T cell antigen presentation assays PloS one High 30001419
2018 MARCH1 ubiquitin-dependent turnover of MHC-II is critical for maintaining homeostasis of lipid rafts and the tetraspanin web in dendritic cells. Lack of MHC-II ubiquitination causes accumulation of excessive MHC-II in the plasma membrane, disrupting lipid rafts and tetraspanin web, and impairing DC engagement of thymocytes for Treg differentiation. MARCH1 KO mice, MHC-II ubiquitination mutant mice, lipid raft fractionation, tetraspanin web analysis, thymic Treg differentiation assays The Journal of cell biology High 29371232
2018 Both DCs and B cells possess a distinct isoform of March-I whose expression is regulated by a promoter located within the March-I gene. A core APC-specific promoter drives March-I expression in DCs and B cells but not fibroblasts; downstream regulatory elements in the first coding exon confer activation-induced down-regulation in APCs. March-I promoter-GFP reporter assays, promoter truncation analysis, activated DCs and B cells The Journal of biological chemistry Medium 29378848
2020 March1 inhibits MAVS/STING/TRIF-induced type I interferon signaling in vitro and in vivo. In malaria-infected hosts, March1 deficiency reduces IFN-I production by activating inhibitors SOCS1, USP18, and TRIM24 and altering immune cell populations, revealing a role in innate immune signaling beyond antigen presentation. March1 KO mice, Plasmodium yoelii infection model, type I IFN signaling assays, in vitro MAVS/STING/TRIF stimulation Proceedings of the National Academy of Sciences of the United States of America Medium 32606244
2020 MARCH1 ubiquitination-deficient DCs are poor stimulators of naive CD4 T cells and secrete IL-12 in response to LPS poorly, despite high surface pMHC-II. These functional and gene transcription defects are cell-intrinsic and are reversed by LPS activation. Single-cell RNA sequencing demonstrates that these DCs have an altered gene expression signature. MHC-II ubiquitination-mutant mouse DCs, naive CD4 T cell stimulation assays, scRNA-seq, IL-12 secretion assays Journal of immunology (Baltimore, Md. : 1950) High 33318291
2021 MARCH1 regulates MHC-II and CD86 specifically in professional and atypical antigen-presenting cells of hematopoietic origin (including neutrophils, eosinophils, monocytes) but not in non-hematopoietic cells, where MARCH8 operates. Unbiased proteomic profiling of the plasma membrane established CD86 and MHC-II as the primary in vivo substrates of MARCH1. MARCH1 and MARCH8 KO mice, unbiased plasma membrane proteomic profiling of primary immune cells Current research in immunology High 35492398
2021 DC induction of TH2 cells depends on MARCH1 ubiquitin ligase in lymph node-resident DCs. The pro-TH2 effect requires ubiquitin acceptor sites of both MHC-II and CD86 (the two MARCH1 substrates), and depends on TCR signaling and GATA-3 induction from naive CD4 T cells by LN-resident (not migratory) DCs. MARCH1 KO mice, MHC-II and CD86 ubiquitin-acceptor site mutant mice, TH2 differentiation assays, DC subset depletion, GATA-3 expression analysis Science immunology High 34652961
2021 MARCH1 promotes OX40L expression in allergen-stimulated dendritic cells by ubiquitinating and degrading HDAC11. HDAC11 normally combines with KLF4 to decrease OX40L promoter activity; MARCH1-driven HDAC11 degradation thus de-represses OX40L expression. Co-immunoprecipitation, ubiquitination assays, luciferase promoter assays, immunofluorescence co-localization, Western blot in DCs from asthmatic patients and animal models Journal of asthma and allergy Medium 34385821
2021 MARCH1 recognizes CD86 through a specific surface in the hydrophobic core of the CD86 transmembrane domain, prominently featuring a proline at position 254, distinct from the recognition mode of viral KSHV MIR2 which requires an aspartic acid in the extracellular juxtamembrane region. This defines the MARCH1 substrate recognition mechanism for CD86. Deep mutational scanning of CD86 transmembrane domain, functional downregulation assays The Journal of biological chemistry High 34157285
2022 MARCH1 isoform 1 (MARCH1.1) restricts influenza A virus (IAV) replication whereas isoform 2 (MARCH1.2) does not. The 16 N-terminal residues of MARCH1.2's cytoplasmic domain suppress IAV restriction activity, as deletion of these residues restores IAV inhibition. Doxycycline-inducible MARCH1 isoform overexpression, viral titer assays, sequential N-terminal deletion mapping Viruses Medium 36423158
2022 MARCH1 mediates ubiquitination and degradation of the transferrin receptor (TfR) during HCMV infection, regulating cellular iron levels and the labile iron pool. MARCH1 knockdown leads to decreased infectious viral titers and increased ROS, lipid peroxidation, and mitochondrial dysfunction. MARCH1 knockdown, TfR expression analysis, labile iron pool measurement, viral titer assays, ROS and lipid peroxidation assays during HCMV infection Journal of virology Medium 35045264
2023 MARCHF1 acts as a novel E3 ligase for GPX4, promoting its ubiquitination and degradation, thereby inducing ferroptosis. BaP/BPDE exposure upregulates MARCHF1 to promote GPX4 degradation in endothelial cells. MARCHF1 overexpression/knockdown, GPX4 ubiquitination assay, ferroptosis assays in HUVECs and mouse miscarriage model Environment international Medium 37802009
2024 MARCH1 and MARCH2 retain Ebola virus glycoprotein (GP) at the trans-Golgi network by interacting with the furin P domain, blocking furin cleavage of EBOV GP and impairing pseudotyped virus infectivity. MARCH1/2 overexpression, EBOV GP-pseudotyped virus infectivity assays, furin co-immunoprecipitation, subcellular localization analysis Journal of medical virology Medium 38299743
2024 MARCH1 interacts with TBK1 and promotes K63-linked ubiquitination of TBK1, which attenuates TBK1 interaction with mTOR and thereby inhibits growth factor-induced mTOR signaling. MARCH1 also interacts with STING. MARCH1 deficiency-induced faster proliferation is reversed by mTOR, STING, or TBK1 inhibition. Co-immunoprecipitation, denatured Co-IP for ubiquitination, MARCH1 overexpression/knockdown, mTOR signaling assays, clonogenic and wound healing assays BMC cancer Medium 39061024
2024 MARCH1 mediates ubiquitination and degradation of PCSK9 in brain neurons under ischemic conditions. MARCH1-mediated PCSK9 downregulation reduces brain damage by inhibiting NLRP3 inflammasome activation and pyroptosis, and by upregulating LDLR. Cycloheximide assay, co-immunoprecipitation, MARCH1/PCSK9 ectopic expression and knockdown, MCAO/R mouse model and OGD/R neuronal model Mammalian genome Medium 39115562
2025 MARCH1 interacts with GABAB receptors specifically under ischemic/excitotoxic conditions and downregulates plasma membrane GABAB receptor levels by inhibiting fast receptor recycling. An interfering peptide blocking the MARCH1/GABAB interaction restored receptor expression and prevented progressive neuronal death. Co-immunoprecipitation, MARCH1 upregulation assays under ischemia, plasma membrane receptor quantification, interfering peptide treatment, neuronal viability assays Scientific reports Medium 39779794
2025 MARCHF1 interacts with and promotes ubiquitination and degradation of PHLPP2 in oral squamous cell carcinoma cells, enhancing cell proliferation and suppressing apoptosis. Co-immunoprecipitation, ubiquitination assay, MARCH1 knockdown/overexpression, proliferation and apoptosis assays, in vivo tumor grafting Clinical & translational oncology Medium 35122633
2025 CD83 suppresses endogenous March-I-dependent MHC-II ubiquitination, endocytosis, and degradation in mouse spleen DCs. Endogenous March-I protein is expressed at very low levels (~500 molecules/cell in DCs) with a very short half-life; March-I mRNA, protein, and MHC-II ubiquitination are rapidly terminated upon DC or B cell activation. V5 epitope knock-in to endogenous March-I gene, quantitative flow cytometry, March-I half-life measurement, activated DC/B cell functional assays Proceedings of the National Academy of Sciences of the United States of America High 40397676
2025 MARCHF1 interacts with REST (repressor element-1 silencing transcription factor) and promotes its ubiquitination and degradation, thereby de-repressing transcription of mitochondrial transcription factor TFAM, supporting mitochondrial function and breast cancer cell proliferation. Co-immunoprecipitation, ubiquitination assay, MARCHF1 knockdown/overexpression, TFAM mRNA analysis, mitochondrial function assays, in vivo tumor model Cell biology international Medium 39428668
2025 MARCHF1 interacts with and promotes ubiquitination-mediated degradation of MYCT1, a candidate tumor suppressor, facilitating AML cell proliferation and inhibiting apoptosis and differentiation. POU2F2 transcription factor positively regulates MARCH1 transcription in AML. Co-immunoprecipitation, ubiquitination assay, MARCH1 knockdown/overexpression, MARCH1 promoter analysis, AML mouse in vivo model Oncogene Medium 40533483
2025 SARS-CoV-2 M protein interacts with GPX4 (at R72 residue) and promotes its degradation via MARCHF1 E3 ubiquitin ligase, leading to ferroptosis through the MARCHF1-GPX4 axis. Co-immunoprecipitation, GPX4-M interaction mapping (R72 mutation), MARCHF1-dependent ubiquitination assay, ferroptosis assays Journal of medical virology Medium 40186530
2023 MARCH1 restricts HIV infectivity in macrophages by limiting incorporation of HIV envelope glycoproteins into nascent virions. HIV-1 Vpu counteracts this restriction by inducing microRNAs-25 and -93 that downregulate MARCH1 mRNA, via hijacking the cellular β-catenin pathway. miRNA-25/93 induction assays, MARCH1 mRNA knockdown, viral infectivity assays, β-catenin pathway analysis in macrophages mBio Medium 37773002

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proceedings of the National Academy of Sciences of the United States of America 204 18305173
2011 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. The Journal of experimental medicine 187 21220452
2008 Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. European journal of immunology 137 18389477
2015 Interleukin 10 (IL-10)-mediated Immunosuppression: MARCH-I INDUCTION REGULATES ANTIGEN PRESENTATION BY MACROPHAGES BUT NOT DENDRITIC CELLS. The Journal of biological chemistry 133 26408197
2016 MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels. Nature communications 74 27577745
2013 Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Journal of immunology (Baltimore, Md. : 1950) 71 24218453
2013 MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells. The Journal of experimental medicine 69 23712430
2015 Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells. Proceedings of the National Academy of Sciences of the United States of America 58 26240324
2023 BaP/BPDE suppressed endothelial cell angiogenesis to induce miscarriage by promoting MARCHF1/GPX4-mediated ferroptosis. Environment international 56 37802009
2009 Discrete domains of MARCH1 mediate its localization, functional interactions, and posttranscriptional control of expression. Journal of immunology (Baltimore, Md. : 1950) 56 19880452
2009 Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 53 19917682
2019 Goat membrane associated ring-CH-type finger 1 (MARCH1) mRNA expression and association with litter size. Theriogenology 47 30711644
2016 Silencing MARCH1 suppresses proliferation, migration and invasion of ovarian cancer SKOV3 cells via downregulation of NF-κB and Wnt/β-catenin pathways. Oncology reports 41 27633480
2012 Autoregulation of MARCH1 expression by dimerization and autoubiquitination. Journal of immunology (Baltimore, Md. : 1950) 39 22508929
2020 The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation. Proceedings of the National Academy of Sciences of the United States of America 38 32606244
2018 MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway. PloS one 36 30001419
2012 Francisella tularensis elicits IL-10 via a PGE₂-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation. PloS one 34 22615981
2020 Resveratrol inhibits the malignant progression of hepatocellular carcinoma via MARCH1-induced regulation of PTEN/AKT signaling. Aging 33 32530437
2019 Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway. Molecules (Basel, Switzerland) 33 30678274
2016 MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice. Journal of immunology (Baltimore, Md. : 1950) 33 27940660
2018 March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity. Nature communications 31 30154416
2018 Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I. The Journal of biological chemistry 29 29414787
2020 5-FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1. Cell biology international 27 33085122
2012 MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression. Cytokine 26 22503116
2021 Myricetin Induces Autophagy and Cell Cycle Arrest of HCC by Inhibiting MARCH1-Regulated Stat3 and p38 MAPK Signaling Pathways. Frontiers in pharmacology 25 34733155
2017 Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls. BMC genetics 25 28673243
2021 Lymph node-resident dendritic cells drive TH2 cell development involving MARCH1. Science immunology 21 34652961
2019 ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653. Aging 21 31819015
2021 Sinomenine Suppresses Development of Hepatocellular Carcinoma Cells via Inhibiting MARCH1 and AMPK/STAT3 Signaling Pathway. Frontiers in molecular biosciences 19 34179090
2018 March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation. Journal of immunology research 19 29854835
2010 MARCH-I: a new regulator of dendritic cell function. Molecules and cells 18 20213309
2024 Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain. Journal of medical virology 17 38299743
2018 MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells. The Journal of cell biology 16 29371232
2018 The E3 ubiquitin ligase MARCH1 regulates glucose-tolerance and lipid storage in a sex-specific manner. PloS one 16 30356278
2022 MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 35122633
2013 Tollip-induced down-regulation of MARCH1. Results in immunology 13 24600555
2025 Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling. Recent patents on anti-cancer drug discovery 12 38243928
2020 Ubiquitination of MHC Class II by March-I Regulates Dendritic Cell Fitness. Journal of immunology (Baltimore, Md. : 1950) 12 33318291
2012 Identification of a novel motif that affects the conformation and activity of the MARCH1 E3 ubiquitin ligase. Journal of cell science 11 23264739
2023 Regulation of MHC class II and CD86 expression by March-I in immunity and disease. Current opinion in immunology 10 37075597
2021 Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8. Current research in immunology 10 35492398
2018 A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene. The Journal of biological chemistry 10 29378848
2011 Environmental epigenomics and disease susceptibility. Keystone symposia on molecular and cellular biology. The Grove Park Hotel & Spa, Ashville, NC, USA, 27 March–1 April 2011. Epigenomics 10 22122336
2022 The Immune-Specific E3 Ubiquitin Ligase MARCH1 Is Upregulated during Human Cytomegalovirus Infection to Regulate Iron Levels. Journal of virology 9 35045264
2021 Human and viral membrane-associated E3 ubiquitin ligases MARCH1 and MIR2 recognize different features of CD86 to downregulate surface expression. The Journal of biological chemistry 9 34157285
2021 E3 Ubiquitin Ligase March1 Facilitates OX40L Expression in Allergen-Stimulated Dendritic Cells Through Mediating the Ubiquitination of HDAC11. Journal of asthma and allergy 9 34385821
2013 Altered MARCH1 ubiquination-regulated dendritic cell immune functions during the early stage of zymosan-induced multiple organ dysfunction syndrome (MODS) in mice. Immunology letters 8 23305794
2024 E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation. Mammalian genome : official journal of the International Mammalian Genome Society 7 39115562
2023 MicroRNA-25/93 induction by Vpu as a mechanism for counteracting MARCH1-restriction on HIV-1 infectivity in macrophages. mBio 7 37773002
2023 Exosome‑delivered miR‑486‑3p inhibits the progression of osteosarcoma via sponging CircKEAP1/MARCH1 axis components. Oncology letters 7 38058466
2022 Isoforms of Human MARCH1 Differ in Ability to Restrict Influenza A Viruses Due to Differences in Their N Terminal Cytoplasmic Domain. Viruses 7 36423158
2024 MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network. Veterinary microbiology 6 38936155
2022 MARCH1 promotes the growth and maintaining of stem cell-like characteristics of gastric cancer cells by activating the Wnt/β-catenin signaling pathway. Tissue & cell 6 35985246
2021 March1-overexpressed dendritic cells downregulate Th1/Th2 ratio in asthma through promoting OX40L. International immunopharmacology 6 34923421
2024 MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1. BMC cancer 4 39061024
2022 MARCH1 Controls an Exhaustion-like Program of Effector CD4+ T Cells Promoting Allergic Airway Inflammation. ImmunoHorizons 4 36100368
2020 Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice. Frontiers in immunology 4 32973799
2022 Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy. Theranostics 3 36451862
2025 The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling. Scientific reports 2 39779794
2025 SARS-CoV-2 Membrane Protein Induces MARCHF1/GPX4-Mediated Ferroptosis by Promoting Lipid Accumulation. Journal of medical virology 2 40186530
2025 MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation. Oncogene 2 40533483
2024 MARCH-I: A negative regulator of dendritic cell maturation. Experimental cell research 2 38331309
2022 Induced overexpression of MARCH-1 in human macrophages altered to M2 phenotype for suppressing inflammation process. Iranian journal of basic medical sciences 2 35656075
2021 A Novel 4q32.3 Deletion in a Child: Additional Signs and the Role of MARCH1. Journal of pediatric genetics 2 34853711
2025 CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation. Proceedings of the National Academy of Sciences of the United States of America 1 40397676
2021 RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I. Frontiers in cellular and infection microbiology 1 33537243
2011 MARCH-I expression in cord blood CD34+KDR+ cells. Clinical biochemistry 1 21385572
2026 MARCH1 attenuates lung adenocarcinoma by blocking macrophage M2 polarization and cisplatin resistance through reducing SLC25A17 stability. Integrative biology : quantitative biosciences from nano to macro 0 41758657
2026 MARCH1 Deletion Attenuates HFpEF by Promoting Adipose Beiging. Comprehensive Physiology 0 41986908
2025 HIV-2 glycoproteins upregulate microRNAs 25 and 93 to counter the MARCH1 antiviral effect in macrophages. Journal of virology 0 41283654
2025 MARCHF1-mediated SULF1 degradation blocks THBS2/TGF-β/SMAD2/3 signaling to reverse colon cancer metastasis and 5-FU resistance. iScience 0 41550717
2024 MARCHF1 promotes breast cancer through accelerating REST ubiquitylation and following TFAM transcription. Cell biology international 0 39428668