Affinage

AMFR

E3 ubiquitin-protein ligase AMFR · UniProt Q9UKV5

Length
643 aa
Mass
73.0 kDa
Annotated
2026-06-09
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AMFR (gp78) is an ER membrane-embedded RING-H2 E3 ubiquitin ligase that nucleates a multidomain degradation machine and serves as a central hub for ER-associated degradation (ERAD), mitochondrial quality control, and innate immune signaling (PMID:11724934, PMID:16407162). Catalytically, gp78 requires three cooperating elements: a RING finger, a ubiquitin-binding CUE domain, and a G2BR site that binds the E2 Ube2g2 at a region distinct from the RING; loss of any one abolishes ubiquitylation and substrate degradation (PMID:16407162). G2BR binding drives an allosteric, ~50-fold increase in E2-RING affinity and primes Ube2g2 through redistribution of its conformational states, while the G2BR and CUE domains together extend polyubiquitin chains from the distal end in cis (PMID:19560420, PMID:25409783, PMID:28434917). gp78 couples ubiquitination to extraction by binding p97/VCP through a VIM motif that docks the ND1 domain and recruits p97 to the ER for retrotranslocation, with Ufd1 acting as a cofactor that enhances ligase activity (PMID:16987818, PMID:15331598, PMID:17681147). Through this machinery gp78 executes sterol-regulated degradation of HMG-CoA reductase and Insig-1 — bridged by Insig-1 and operating in parallel with the ligases Trc8 and RNF145 — and degrades substrates including CD3-delta, CFTRΔf508, and KAI1/CD82, the last linking gp78 to metastasis and proliferation control (PMID:16168377, PMID:17043353, PMID:22143767, PMID:30543180, PMID:18037895, PMID:20089858). For some substrates gp78 acts as an E4-like factor downstream of an initiating E3, recognizing pre-conjugated ubiquitin via its CUE domain and operating in a post-retrotranslocation step in cooperation with the BAG6 complex (PMID:18216283, PMID:26424800). Beyond ERAD, gp78 ubiquitinates mitofusins Mfn1/Mfn2 to drive mitochondrial fission and Parkin-independent mitophagy (PMID:23427266), and it regulates innate immunity by catalyzing linkage-specific ubiquitination of signaling proteins — K27-linked ubiquitination of STING to recruit TBK1, K27-linked modification of TAB3 to activate TAK1/NF-κB, K48-linked ubiquitination of CIS, and mixed-linkage modification of NLRP3 to restrain inflammasome activation (PMID:25526307, PMID:36593296, PMID:35333296, PMID:35110683). gp78 activity is tuned by phosphorylation (p38 at S538, CDK5 at S516) and by trans-ubiquitination from MGRN1, Hrd1, and TRIM25 (PMID:26337390, PMID:28528366, PMID:26743086, PMID:19835843, PMID:24810856). Bi-allelic truncating AMFR variants cause autosomal recessive hereditary spastic paraplegia through disrupted lipid homeostasis and lipid droplet accumulation (PMID:37119330).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1997 Medium

    Before its enzymatic role was known, gp78 was placed in a defined ER subdomain, establishing the membrane platform on which its later degradation functions operate.

    Evidence Immunofluorescence, confocal and electron microscopy with ilimaquinone/nocodazole in mammalian cells defining the smooth-ER 'AMF-R tubule'

    PMID:9365274

    Open questions at the time
    • Did not define molecular function
    • Relationship of this subdomain to ERAD machinery not established
  2. 2001 High

    Established that gp78 is an intrinsic ER-membrane RING-finger E3 ligase that recruits a specific E2 and degrades an ERAD substrate, defining its core catalytic identity.

    Evidence Overexpression and dominant-negative RING mutants, ubiquitination and CD3-delta degradation assays in mammalian cells

    PMID:11724934

    Open questions at the time
    • E2 recruitment site distinct from RING not yet mapped
    • Full substrate range unknown
    • Coupling to extraction machinery unaddressed
  3. 2004 High

    Showed how ubiquitination is coupled to substrate extraction by demonstrating a dedicated p97/VCP-interacting domain required for retrotranslocation and degradation.

    Evidence Co-IP, domain deletion, RNAi and CD3-delta degradation assays

    PMID:15331598

    Open questions at the time
    • Precise motif mediating p97 binding not yet identified
    • Cofactor requirements unresolved
  4. 2006 High

    Defined the three-domain architecture (RING, CUE, G2BR) required for catalysis and identified the VIM motif that directly docks the p97 ND1 domain, resolving the molecular logic of the gp78 degradation module.

    Evidence Systematic domain mutagenesis, ubiquitination and glycosylation/degradation assays, Co-IP and RNAi of Ufd1/p97

    PMID:16407162 PMID:16987818

    Open questions at the time
    • Mechanism by which CUE and G2BR cooperate not yet resolved
    • Generality across substrates untested
  5. 2006 High

    Placed gp78 at the heart of sterol-regulated lipid metabolism by showing it degrades HMGCR and Insig-1 via Insig-1 bridging, linking ERAD to cholesterol homeostasis.

    Evidence Co-IP, RNAi, sterol-regulated ubiquitination and pulse-chase assays

    PMID:16168377 PMID:17043353

    Open questions at the time
    • Redundancy with other HMGCR ligases not yet assessed
    • Quantitative contribution to flux unclear
  6. 2007 High

    Refined the extraction step by showing Ufd1 directly binds gp78 and uses distinct mono- and poly-ubiquitin sites to enhance ubiquitination and a post-ubiquitination step, and extended gp78's substrate range to the metastasis suppressor KAI1.

    Evidence Co-IP, domain mutagenesis, in vitro/in vivo ubiquitination, pulse-chase, RING mutant and in vivo metastasis assays

    PMID:17681147 PMID:18037895

    Open questions at the time
    • In vivo physiological significance of Ufd1 cofactor role limited to assays
    • KAI1 degradation mechanism in tumors not fully defined
  7. 2008 High

    Revealed that gp78 can act as an E4-like elongation factor downstream of an initiating E3, recognizing pre-conjugated monoubiquitin through its CUE domain.

    Evidence Domain swapping, in vitro polyubiquitylation, RMA1 knockdown epistasis and Co-IP using CFTRΔf508

    PMID:18216283

    Open questions at the time
    • Which substrates use E3 vs E4 mode not generalized
    • Structural basis of CUE chain recognition unresolved
  8. 2009 High

    Provided the structural and mechanistic basis for E2 activation, showing G2BR allosterically primes Ube2g2 and dramatically boosts RING affinity.

    Evidence NMR structure, SPR, in vitro ubiquitylation and mutagenesis

    PMID:19560420

    Open questions at the time
    • Dynamics of the allosteric transition not yet captured
    • In-cell relevance of affinity gain untested
  9. 2009 Medium

    Expanded gp78's role into neurodegeneration-associated proteostasis and revealed cross-regulation among ER ligases and engagement of toxin retrotranslocation.

    Evidence Co-IP, overexpression/knockdown, aggregation assays (SOD1, ataxin-3); Hrd1-null MEFs; cholera toxin/PDI binding and retro-translocation assays

    PMID:19661182 PMID:19835843 PMID:19864457

    Open questions at the time
    • Single-lab functional studies
    • Hierarchy of Hrd1/gp78/Derlin-1 not fully resolved
    • Non-ubiquitination roles partly undefined
  10. 2011 Medium

    Mapped the multi-ligase, multi-cofactor network controlling sterol-accelerated HMGCR degradation and identified the SPFH2-TMUB1 scaffold supporting gp78 function.

    Evidence Single and combined RNAi of gp78/Trc8, Co-IP and sterol-induced ubiquitination/degradation assays

    PMID:21343306 PMID:22143767

    Open questions at the time
    • Compensation mechanisms among ligases not mechanistically explained
    • Stoichiometry of SPFH2-TMUB1-gp78 complex unknown
  11. 2013 High

    Established a non-ERAD role for gp78 in mitochondrial dynamics and quality control, degrading mitofusins to drive Parkin-independent mitophagy, with AMF endocytosis as an upstream modulator.

    Evidence WT vs RING-mutant overexpression, CCCP depolarization, Atg5/Parkin/Mfn siRNA, LC3 marker; pharmacological/genetic dissection of AMF uptake and Rac1

    PMID:23427266 PMID:23690547

    Open questions at the time
    • How a single ligase coordinates ERAD vs mitophagy spatially unresolved
    • Physiological mitophagy contexts in vivo limited
  12. 2013 Medium

    Opened the immune-regulatory dimension by showing gp78 at the ER-mitochondria interface controls MAVS and RLR antiviral signaling via both ERAD and ERAD-independent mechanisms.

    Evidence Co-IP domain mapping, mutant constructs, RNAi, IFN reporter and VSV infection assays

    PMID:24285545

    Open questions at the time
    • Single lab
    • Relative contribution of degradative vs non-degradative arms unquantified
  13. 2014 Medium

    Defined gp78 substrate-specificity safeguards and chain-elongation chemistry — DUB-mediated protection of machinery, additional substrates, and distal-end chain extension via cooperative G2BR/CUE action.

    Evidence Co-IP, in vitro chain assembly and polyubiquitylation, site/domain mutagenesis (Ubl4A/USP13, HERP, HSPA5, AMF/TRIM25)

    PMID:24424410 PMID:24496447 PMID:24810856 PMID:25409783 PMID:26119938

    Open questions at the time
    • Each substrate validated largely in single labs
    • In vivo relevance of machinery-protective USP13 axis limited
  14. 2014 High

    Defined a linkage-specific signaling output by showing the AMFR-INSIG1 complex catalyzes K27-linked STING ubiquitination to recruit TBK1, establishing gp78 as a positive regulator of cytosolic-DNA antiviral immunity.

    Evidence Co-IP, ubiquitination site mapping, RNAi, Insig1 myeloid-specific knockout mice and HSV-1 infection

    PMID:25526307

    Open questions at the time
    • Structural basis of K27 specificity unknown
    • How INSIG1 redirects gp78 to immune substrates unclear
  15. 2015 Medium

    Clarified gp78's position in the ERAD pathway hierarchy (downstream of Hrd1, post-retrotranslocation with BAG6) and identified p38-mediated S538 phosphorylation as a switch limiting mitofusin degradation.

    Evidence shRNA/CRISPR, retrotranslocation and ubiquitination assays; MS phosphosite mapping, phosphomimetic mutants, p38 inhibitor and morphology imaging

    PMID:26337390 PMID:26424800

    Open questions at the time
    • Single-lab epistasis
    • How S538 phosphorylation alters substrate engagement without affecting in vitro activity unresolved
  16. 2016 Medium

    Showed gp78 abundance is gated by trans-ubiquitination, with MGRN1 using K11-linked chains and cytosolic Ca2+ relieving this brake to license mitophagy.

    Evidence Co-IP, K11 linkage-specific ubiquitination, Ca2+ chelation and MGRN1 catalytic mutants

    PMID:26743086

    Open questions at the time
    • Single lab
    • How Ca2+ disrupts MGRN1-gp78 interaction mechanistically unknown
  17. 2017 Medium

    Detailed the dynamic energy landscape of E2 activation and a CDK5 phosphodegron at S516 that destabilizes gp78 with neuroprotective consequences.

    Evidence NMR conformational dynamics with mutagenesis/ubiquitylation; in vitro kinase assay, S516 mutants, MPTP/MPP+ Parkinson's models

    PMID:28434917 PMID:28528366

    Open questions at the time
    • Allosteric model is structural/in vitro
    • S516 phosphodegron in vivo relevance limited to disease models in single lab
  18. 2018 High

    Through unbiased genome-wide screening, defined the redundant ligase network (RNF145, gp78, Hrd1) governing HMGCR degradation and sterol responsiveness.

    Evidence Genome-wide CRISPR screens, endogenous HMGCR reporter, siRNA and ubiquitination/sterol assays

    PMID:30543180

    Open questions at the time
    • Division of labor among the three ligases under physiological sterol flux not fully quantified
  19. 2021 High

    Established AMFR as a cell-surface receptor (for CCL1) coupling ligand binding to Spry1 ubiquitination and Ras-ERK-driven fibrosis, broadening its activity beyond intracellular degradation.

    Evidence MS of CCL1 complexes, fibroblast AMFR deletion, ubiquitination and Ras-ERK assays, pulmonary fibrosis mouse models

    PMID:34407391

    Open questions at the time
    • Reconciliation of receptor role with ER-membrane topology unaddressed
    • Direct vs adaptor-mediated CCL1 binding unclear
  20. 2022 High

    Expanded linkage-specific immune and transporter regulation: K48 ubiquitination of CIS promoting STAT5/GM-CSF, mixed-linkage NLRP3 ubiquitination restraining inflammasome, and non-degradative K542 ubiquitination promoting EAAT2 oligomerization; plus a K27/K33 ER-phagy axis on FAM134B.

    Evidence Co-IP, linkage-specific ubiquitination, conditional/knockout mice, signaling and oligomer assays, ER-phagy flux and disease models

    PMID:35110683 PMID:35333296 PMID:35938532 PMID:40673870

    Open questions at the time
    • How AMFR selects K48 vs mixed vs non-degradative linkages on different substrates unresolved
    • Some readouts single-lab
  21. 2023 Medium

    Connected AMFR to human Mendelian disease and infection-driven inflammation: bi-allelic truncating variants cause hereditary spastic paraplegia via lipid dysregulation, and AMFR drives TAB3 K27 ubiquitination/TAK1-NF-κB during S. aureus infection.

    Evidence Patient WGS, patient fibroblasts/neural stem cells with rescue, amfra zebrafish and statin treatment; CRISPR screen, Co-IP, K27/K649 ubiquitination, pneumonia models

    PMID:36593296 PMID:37119330

    Open questions at the time
    • HSP mechanism linking lipid droplet accumulation to neurodegeneration incompletely defined
    • Single disease publication
  22. 2024 Medium

    Extended AMFR's antiviral and immunometabolic roles: a patient STING-pathway variant (R594C) impairs K27-STING ubiquitination/trafficking, AMFR K48-ubiquitinates flaviviral NS2A to suppress ER-phagy, and cholesterol/p38 control AMFR-mediated PDL1 degradation in cancer.

    Evidence WT vs variant ubiquitination/trafficking/reporter and reconstitution; viral mutant, organoid and mouse infection models; Co-IP, cholesterol manipulation and xenografts

    PMID:38277122 PMID:39231894 PMID:39505910

    Open questions at the time
    • Single case study for R594C
    • p38/cholesterol regulation of substrate choice mechanistically incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single ER-membrane ligase achieves its diverse linkage-specific outputs (K11/K27/K33/K48/mixed) and partitions among ERAD, mitophagy, ER-phagy, receptor signaling, and surface-receptor functions across cell types.
  • No structural model explains linkage-type selection
  • Spatial/temporal control distinguishing competing functions unknown
  • Mechanism enabling extracellular ligand reception by an ER-resident ligase undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0031386 protein tag activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005739 mitochondrion 3 GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3
Partners
FAM134BINSIG1MFN1STING1TAB3UBE2G2UFD1VCP
Complex memberships
gp78-Insig-1 E3 complexgp78-SPFH2-TMUB1 complexgp78-p97/VCP-Ufd1 retrotranslocation module

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 gp78/AMFR is a RING finger-dependent E3 ubiquitin ligase intrinsic to the ER membrane. It recruits the E2 enzyme MmUBC7 through a region distinct from the RING finger, can auto-ubiquitinate itself for proteasomal degradation, and mediates degradation of the ERAD substrate CD3-delta in a RING finger- and MmUBC7-dependent manner. Overexpression and dominant-negative (RING finger mutant) constructs in mammalian cells; ubiquitination assays; CD3-delta degradation assay Proceedings of the National Academy of Sciences of the United States of America High 11724934
2005 gp78 associates with Insig-1 (but not Insig-2) and is required for sterol-regulated ubiquitination and degradation of HMG-CoA reductase (HMGCR). gp78 couples regulated ubiquitination to degradation by also binding VCP/p97, with Insig-1 serving as a bridge between gp78/VCP and the reductase substrate. Co-immunoprecipitation; RNAi knockdown of gp78; sterol-regulated ubiquitination and pulse-chase degradation assays Molecular cell High 16168377
2004 gp78 physically interacts with p97/VCP and enhances p97/VCP-polyubiquitin association, facilitating retrotranslocation of ubiquitinated ERAD substrates. A specific p97/VCP-interacting domain on gp78 is required; its deletion prevents CD3-delta degradation and causes accumulation of polyubiquitinated CD3-delta. Co-immunoprecipitation; domain deletion analysis; RNAi knockdown; CD3-delta degradation assay The Journal of biological chemistry High 15331598
2006 Efficient gp78-mediated ERAD requires three functional domains: the RING finger, a ubiquitin-binding CUE domain, and a specific Ube2g2-binding site (G2BR) distinct from the RING finger. Disruption of any one of these domains abolishes gp78-mediated ubiquitylation and protein degradation, with substrates accumulating in their fully glycosylated ER-resident forms. Domain mutagenesis; in vivo ubiquitination assays; glycosylation analysis as ERAD readout Proceedings of the National Academy of Sciences of the United States of America High 16407162
2006 gp78 contains a novel VIM (VCP-interacting motif) that mediates direct interaction with the ND1 domain of p97/VCP, recruits p97/VCP to the ER, and is required for gp78-mediated substrate degradation. Inhibition of p97/VCP (but not Ufd1 alone at high gp78 overexpression levels) stabilizes CD3-delta, suggesting gp78 can operate in a Ufd1-independent pathway in parallel with the canonical VCP-Ufd1-Npl4 mechanism. Domain deletion and mutation; co-immunoprecipitation; RNAi of Ufd1 and p97/VCP; CD3-delta degradation assay The Journal of biological chemistry High 16987818
2006 gp78 mediates sterol-regulated degradation of Insig-1 (but not Insig-2) in sterol-depleted cells. Sterols prevent Insig-1 ubiquitination by displacing gp78 from Insig-1 through sterol-induced binding of Scap to Insig-1, explaining ER retention of Scap while reductase is ubiquitinated. Co-immunoprecipitation; RNAi knockdown of gp78; ubiquitination assays; pulse-chase protein stability assays The Journal of biological chemistry High 17043353
2007 Ufd1 directly interacts with gp78 and functions as a cofactor that enhances gp78 E3 activity. The monoubiquitin-binding site in Ufd1 is required for enhancement of gp78 ubiquitination activity, while the polyubiquitin-binding site is critical for a post-ubiquitination step in ERAD. Ufd1 accelerates ubiquitination and degradation of HMG-CoA reductase. Co-immunoprecipitation; domain mutagenesis; in vitro and in vivo ubiquitination assays; pulse-chase degradation assays Cell metabolism High 17681147
2007 gp78 associates with and ubiquitinates the transmembrane metastasis suppressor KAI1 (CD82), targeting it for proteasomal degradation. This prometastatic activity requires the E3 ligase activity of gp78. Suppression of gp78 increases KAI1 abundance and reduces metastatic potential. Co-immunoprecipitation; RNAi knockdown; in vivo metastasis assays; RING finger mutant; tissue microarray Nature medicine High 18037895
2008 gp78 participates in ERAD of CFTRΔf508 by recognizing monoubiquitin already conjugated to CFTRΔf508 via its CUE domain and catalyzing further polyubiquitylation in an E4-like manner. RMA1 functions as the upstream E3 and gp78 acts downstream as an E4-like polyubiquitylation factor. Domain swapping/deletion analysis; in vitro polyubiquitylation assay; siRNA knockdown of RMA1; co-immunoprecipitation Molecular biology of the cell High 18216283
2009 The G2BR domain of gp78 binds selectively and with high affinity to the E2 Ube2g2 at a region distinct from E1- and RING-binding sites. This binding causes conformational changes in Ube2g2 affecting ubiquitin loading and produces an ~50-fold increase in E2-RING affinity, markedly increasing ubiquitylation via an allosteric mechanism. NMR structural analysis; surface plasmon resonance; in vitro ubiquitylation assays; mutagenesis Molecular cell High 19560420
2009 gp78 promotes ubiquitination and proteasomal degradation of SOD1 and ataxin-3. gp78 interacts with both proteins; overexpression promotes their ubiquitination and degradation while knockdown stabilizes them. gp78 also suppresses aggregate formation of mutant SOD1 and protects cells from mutant SOD1-induced death. Co-immunoprecipitation; overexpression and siRNA knockdown; ubiquitination assays; aggregation assays Human molecular genetics Medium 19661182
2009 Both Hrd1 and gp78 bind cholera toxin (CTA1 subunit) and protein disulfide isomerase (PDI), and expression of dominant-negative forms of Hrd1 and gp78 or dominant-negative Ube2g2 decreases CTA1 retro-translocation. CT association with Hrd1/gp78 is blocked by dominant-negative Derlin-1, suggesting sequential engagement: CT → Derlin-1 → Hrd1/gp78. Dominant-negative constructs; pulldown/binding studies; retro-translocation assays; RNAi knockdown Molecular biology of the cell Medium 19864457
2009 Hrd1 targets gp78 for proteasomal degradation in a manner independent of gp78's own ubiquitin ligase activity, establishing cross-regulation between the two ER E3 ligases. Reduced Hrd1 increases gp78 levels, which in turn decreases the gp78 substrate Insig-1. Mouse embryonic fibroblasts lacking Hrd1; siRNA knockdown; protein stability assays Biochemical and biophysical research communications Medium 19835843
2010 Mutant huntingtin interacts with gp78 via its HEAT repeats 2&3 binding to the CUE domain of gp78, competitively reducing polyubiquitinated protein binding to gp78 and sterically blocking gp78-p97/VCP interaction, thereby impairing ERAD and inducing ER stress. Polyglutamine expansion aggravates this inhibitory effect. Co-immunoprecipitation; domain mapping; competitive binding assays; ER stress markers PloS one Medium 20126661
2010 gp78 promotes cell proliferation and mammary gland hyperplasia by targeting the metastasis suppressor KAI1 for ERAD. Stable knockdown of gp78 in HEK293 cells increases KAI1 expression and reduces proliferation, an effect rescued by concomitant KAI1 knockdown, placing KAI1 downstream of gp78 in proliferation control. MMTV-gp78 transgenic mice; stable knockdown; KAI1 co-knockdown rescue; BrdU proliferation assay The Journal of biological chemistry Medium 20089858
2011 Sterol-accelerated HMGCR degradation requires interplay of two Insigs and two ubiquitin ligases: gp78 (recruits Insig-1) and Trc8 (recruits both Insig-1 and Insig-2). Combined RNAi knockdown of gp78 and Trc8 produces >90% inhibition of sterol-induced reductase degradation; gp78 knockdown leads to compensatory increases in Trc8 and Insig-1. siRNA knockdown (single and combined); sterol-induced ubiquitination and degradation assays; protein level analysis Proceedings of the National Academy of Sciences of the United States of America High 22143767
2011 gp78 forms a complex with two ER membrane proteins, SPFH2 and TMUB1, where TMUB1 bridges SPFH2 to gp78. RNAi-mediated knockdown of SPFH2 and TMUB1 blunts sterol-induced ubiquitination and degradation of endogenous HMG-CoA reductase. Co-immunoprecipitation; RNAi knockdown; sterol-induced ubiquitination and degradation assays The Journal of biological chemistry Medium 21343306
2012 Gp78 RING finger cysteines undergo S-palmitoylation. Five palmitoyl acyltransferases increase gp78 RING finger palmitoylation. ER-localized DHHC6 overexpression promotes peripheral ER distribution of gp78, while RING finger mutation or palmitoylation inhibition restricts gp78 to the central ER, linking palmitoylation to gp78 subcellular distribution. Palmitoylation assay; PAT overexpression screen; immunofluorescence microscopy; RING finger mutagenesis FEBS letters Medium 22728137
2013 Gp78 overexpression (but not RING mutant) induces mitochondrial fragmentation and ubiquitination plus proteasome-dependent degradation of mitofusins Mfn1 and Mfn2. After mitochondrial depolarization, Gp78 induces mitophagy dependent on ubiquitin ligase activity and Mfn1 (but not Mfn2). Gp78-induced mitophagy is Parkin-independent. Overexpression of wild-type vs RING mutant Gp78; CCCP-induced depolarization; siRNA knockdown of Atg5, Parkin, Mfn1/2; LC3-GFP autophagy marker; OxPhos protein levels Molecular biology of the cell High 23427266
2013 Gp78, localized at the ER-mitochondria interface, regulates MAVS expression and RLR antiviral signaling via two parallel pathways: (1) E3 ubiquitin ligase/ERAD activity directly degrades MAVS; (2) Gp78 RING domain interacts with both N- and C-terminal domains of MAVS and attenuates RLR signaling independently of ERAD. Gp78 depletion enhances type I IFN signaling. Co-immunoprecipitation; Gp78 mutant constructs; RNAi knockdown; IFN reporter assays; VSV infection assay The Journal of biological chemistry Medium 24285545
2013 AMF endocytosis through a PI3K- and dynamin-dependent raft pathway requires Gp78 and stimulates Rac1 activation. AMF uptake inhibits Gp78-induced degradation of mitofusins 1 and 2, thereby preventing Gp78-dependent mitochondrial fission. Gp78 knockdown reduces both AMF-induced Rac1 activation and dynamin-dependent AMF internalization. Dynamin inhibitor; PI3K inhibitor; dominant-negative Rac1; Rac1 inhibitor; Gp78 knockdown; Mfn1/2 protein levels; mitochondrial morphology imaging Journal of cell science Medium 23690547
2014 Upon cytoplasmic DNA stimulation, AMFR is recruited to STING in an INSIG1-dependent manner. The AMFR-INSIG1 E3 complex catalyzes K27-linked polyubiquitination of STING, which serves as a platform for recruiting TBK1 and facilitating TBK1 translocation to perinuclear microsomes. Depletion of AMFR or INSIG1 impairs STING-mediated antiviral gene induction. Co-immunoprecipitation; RNAi knockdown; ubiquitination assays; Insig1 knockout mice (myeloid-specific); HSV-1 infection model Immunity High 25526307
2014 gp78 ubiquitinates not only ERAD substrates but also the machinery protein Ubl4A (component of the Bag6 chaperone complex), leading to irreversible proteolytic inactivation of Bag6. The DUB USP13 associates with gp78 and removes ubiquitin conjugates from Ubl4A to maintain Bag6 functionality and sharpen gp78 substrate specificity. Co-immunoprecipitation; ubiquitination assays; DUB identification; cell-based functional assays for Bag6/ERAD eLife Medium 24424410
2014 After ER stress induction, HERP is rapidly degraded by Ube2g2-gp78-mediated ubiquitylation and proteasomal degradation during ER stress recovery. This requires physical interaction between the CUE domain of gp78 and the UBL domain of HERP, which is essential for HERP degradation in vivo. In vitro polyubiquitylation assay; domain interaction mapping; cell-based degradation assays; siRNA knockdown Journal of cell science Medium 24496447
2014 gp78 interacts with the C-terminal region of HSPA5/GRP78, mediates HSPA5 ubiquitination and degradation, specifically at K447. HDAC6-mediated deacetylation of HSPA5 at K353 promotes GP78 binding and ubiquitination; acetylation at K353 reduces GP78-mediated ubiquitination at K447. Co-immunoprecipitation; site-directed mutagenesis; ubiquitination assays; siRNA knockdown of GP78 and HDAC6 Oncogene Medium 26119938
2014 Polyubiquitylation of autocrine motility factor (AMF/PGI) requires cooperative interaction between gp78 and TRIM25: TRIM25 mediates initial ubiquitylation, then gp78 catalyzes polyubiquitylation in an E4-like manner. TRIM25 also ubiquitinates gp78 itself, modulating gp78 steady-state levels. In vitro polyubiquitylation assay with Ub-DHFR model substrate; co-immunoprecipitation; siRNA knockdown; protein stability assays Oncotarget Medium 24810856
2014 gp78 extends polyubiquitin chains from the distal end through cooperative action of its G2BR and CUE domains: G2BR binds donor Ube2g2~Ub to promote ubiquitin transfer in cis, while the CUE domain binds the growing ubiquitin chain preferentially over monoubiquitin to position the distal ubiquitin correctly for chain elongation. In vitro polyubiquitin chain assembly assays; domain deletion/mutagenesis; binding assays Scientific reports Medium 25409783
2015 gp78 acts downstream of Hrd1 in ERAD: Hrd1 is the essential retrotranslocation/ubiquitination module, while gp78 knockdown does not affect retrotranslocation or initial ubiquitination of ERAD substrates but promotes ERAD via cooperation with the BAG6 chaperone complex in a post-retrotranslocation step. shRNA knockdown; CRISPR-based genetic tools; biochemical retrotranslocation assays; ubiquitination assays; BAG6 co-functional studies Molecular biology of the cell Medium 26424800
2015 p38 MAP kinase phosphorylates gp78 at Ser-538 (S538) in a 14-3-3/WW-domain-containing region at the mitochondria-associated ER. S538 phosphorylation limits gp78-induced mitochondrial fission and Mfn1/Mfn2 degradation, and the phosphomimetic S538D mutation prevents gp78 promotion of ER-mitochondria interaction without affecting in vitro E3 ubiquitin ligase activity. Mass spectrometry phosphopeptide mapping; 3F3A antibody as phosphorylation reporter; phosphomimetic/phosphonull mutagenesis; p38 MAPK inhibitor (SB203580); mitochondrial morphology imaging; in vitro ubiquitin ligase assay Molecular biology of the cell Medium 26337390
2016 MGRN1, a cytosolic E3 ligase, ubiquitylates GP78 in trans via non-canonical K11-linked polyubiquitination, maintaining constitutively low GP78 levels in healthy cells and suppressing mitophagy. Elevated cytosolic Ca2+ (from mitochondrial stress) reduces MGRN1-GP78 interaction and GP78 ubiquitylation, enabling GP78-mediated mitophagy. Co-immunoprecipitation; ubiquitination assays specifying K11 linkage; Ca2+ chelation experiments; MGRN1 catalytic mutants; protein stability assays Journal of cell science Medium 26743086
2017 Conformational dynamics in Ube2g2 reveals that G2BR binding and RING binding of gp78 drive sequential progression toward ubiquitin transfer through redistribution of conformational populations. The G2BR-bound state of Ube2g2 shows allosteric changes that are prerequisite for RING-mediated activation, establishing a dynamic energy landscape model for E2 activation. NMR conformational dynamics analysis; NMR chemical shift perturbation; mutagenesis; in vitro ubiquitylation assays Structure High 28434917
2017 CDK5 directly phosphorylates GP78 at Ser516, promoting ubiquitination and degradation of GP78. GP78 overexpression or interference with Ser516 phosphorylation protects neurons against MPP+-induced cell death in Parkinson's disease models. In vitro kinase assay; site-directed mutagenesis (Ser516); GP78 overexpression and phosphomutants; MPTP/MPP+ cellular and animal models; ubiquitination assays Molecular neurobiology Medium 28528366
2018 RNF145 and gp78 independently co-ordinate HMGCR ubiquitination and degradation. CRISPR genome-wide screens identify that in the absence of both RNF145 and gp78, a third UBE2G2-dependent E3 ligase Hrd1 partially regulates HMGCR. RNF145 is sterol-responsive, accumulates following sterol depletion, and is recruited to HMGCR via Insigs upon sterol addition. CRISPR/Cas9 genome-wide screens; endogenous HMGCR reporter; siRNA knockdown; ubiquitination assays; sterol regulation assays eLife High 30543180
2021 CCL1 binds AMFR as a receptor on fibroblasts, triggering AMFR E3 ligase-mediated ubiquitination of the ERK inhibitor Spry1. This ubiquitination activates Ras-mediated profibrotic protein synthesis, driving fibroblast-to-myofibroblast differentiation and pulmonary fibrosis. Mass spectrometry of CCL1 complexes; AMFR deletion in fibroblasts; ubiquitination assays; Ras-ERK pathway activation assays; mouse models of pulmonary fibrosis Immunity High 34407391
2022 gp78-Insig-1 E3 complex mediates mixed-linkage ubiquitination of NLRP3, inhibiting NLRP3 inflammasome activation by suppressing NLRP3 oligomerization and subcellular translocation. Insig-1 is required for gp78-NLRP3 interaction. gp78 or Insig-1 deficiency in myeloid cells exacerbates NLRP3-dependent inflammation in vivo. Co-immunoprecipitation; ubiquitination assays (linkage specificity); inflammasome activation assays (oligomerization, translocation); myeloid-specific knockout mice; LPS-induced inflammation and alum-induced peritonitis models Cell death and differentiation High 35110683
2022 AMFR, following TSLP stimulation in alveolar macrophages, directly associates with CIS (cytokine-inducible SH2-containing protein) and catalyzes K48-linked polyubiquitination of CIS, blocking CIS inhibition of STAT5 phosphorylation and promoting downstream GM-CSF production that drives Th2/eosinophilic asthma inflammation. Co-immunoprecipitation; K48 linkage-specific ubiquitination assays; AMFR conditional knockout mice; STAT5 phosphorylation assays; GM-CSF ELISA; allergy models The Journal of experimental medicine High 35333296
2022 AMFR mediates K542-specific ubiquitination of EAAT2 (excitatory amino acid transporter 2) that specifically promotes EAAT2 oligomer formation rather than degradation, increasing functional transporter levels. AMFR and EAAT2 oligomer levels are simultaneously decreased in hippocampus of epilepsy models. Co-immunoprecipitation; site-directed mutagenesis (K542); ubiquitination assays; oligomer detection; in vivo epilepsy mouse models; FDA drug screen JCI insight Medium 35938532
2023 AMFR directly interacts with TAK1-binding protein 3 (TAB3) in the ER, inducing K27-linked polyubiquitination of TAB3 at K649, thereby promoting TAK1 activation and intracellular S. aureus-induced NF-κB-mediated inflammation. The S. aureus virulence factor HlgB binds AMFR and modulates this TAB3 signaling. Co-immunoprecipitation; CRISPR-Cas9 screen; ubiquitination assays (K27-linkage); site-directed mutagenesis (K649); TAK1 activation assays; pneumonia mouse models Nature microbiology High 36593296
2023 Bi-allelic truncating variants in AMFR cause autosomal recessive hereditary spastic paraplegia. Loss of AMFR disturbs lipid homeostasis causing lipid droplet accumulation in neural stem cells and patient fibroblasts rescued by AMFR re-expression. In amfra-/- zebrafish, motor neuron branching defects and touch-evoked escape response abnormalities are observed, and statins improve these phenotypes. Patient whole genome sequencing; patient-derived fibroblasts and neural stem cells; AMFR re-expression rescue; electron microscopy (ER morphology); zebrafish amfra knockout; statin treatment Acta neuropathologica Medium 37119330
2023 AMFR promotes proteasomal degradation of HMGCR in response to influenza virus infection and activates innate immunity components TBK1 and IRF3. AMFR knockdown inhibits HMGCR ubiquitination and inactivates TBK1/IRF3 signaling during influenza infection. siRNA knockdown of AMFR; ubiquitination assays; TBK1/IRF3 phosphorylation assays; influenza virus infection model Virology Low 37703797
2024 AMFR variant R594C (patient-derived) results in decreased K27-linked STING ubiquitination and reduced STING trafficking from ER to Golgi compared to wild-type AMFR, impairing type I IFN responses and increasing VZV replication. Lentiviral transduction with wild-type AMFR partially reconstitutes STING-mediated signaling in patient PBMCs. Overexpression of WT vs R594C AMFR; K27 ubiquitination assay; ImageStream STING trafficking assay; IFN-β reporter gene assay; lentiviral reconstitution in patient PBMCs; VZV replication assay Journal of clinical immunology Medium 38277122
2024 AMFR catalyzes K48-linked polyubiquitination of Flavivirus NS2A at K56, and ubiquitinated NS2A binds FAM134B (ER-phagy receptor), with AMFR then orchestrating degradation of the NS2A-FAM134B complex. This AMFR-mediated ubiquitination of NS2A both suppresses ER-phagy and hinders the FAM134B-AMFR axis. A ZIKV K56R mutant lacking ubiquitination shows attenuated pathogenesis. Co-immunoprecipitation; ubiquitination assays (K48 linkage, K56 site mutagenesis); recombinant ZIKV-NS2AK56R; human brain organoids; mouse infection models Nature communications High 39505910
2024 AMFR mediates ubiquitination and proteasomal degradation of PDL1 in hepatocellular carcinoma. Cholesterol suppresses AMFR-mediated PDL1 ubiquitination through the cholesterol/p38 MAPK axis, stabilizing PDL1. Statin-mediated cholesterol reduction restores AMFR-dependent PDL1 degradation and improves PD1 inhibition efficacy in vivo. Co-immunoprecipitation; ubiquitination assays; cholesterol manipulation; p38 MAPK pathway analysis; xenograft tumor model Molecular and cellular biochemistry Medium 39231894
1997 AMFR (gp78) localizes to a distinct smooth ER subdomain called the AMF-R tubule, which is fenestrated, ilimaquinone-sensitive, microtubule-associated, and continuous with rough ER cisternae but distinct from Golgi and ERGIC. This smooth ER subdomain can be selectively disrupted by ilimaquinone and nocodazole. Immunofluorescence microscopy; confocal microscopy; electron microscopy; ilimaquinone and nocodazole treatment; ERGIC-53 co-localization Journal of cell science Medium 9365274
2022 AMFR catalyzes K27-linked (predominant) and K33-linked ubiquitination of FAM134B (ER-phagy receptor), enhancing ER-phagy flux. This AMFR-driven ER-phagy suppresses cardiac fibroblast activation post-MI by inhibiting phosphorylation of mTORC1 downstream targets S6K1 and 4E-BP. AMFR knockout mice; AMFR overexpression in cardiac fibroblasts; ubiquitination assays (K27/K33 linkage); scRNA-seq; mTORC1 pathway assays; ER-phagy flux measurement Advanced science Medium 40673870

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America 366 11724934
2005 Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Molecular cell 314 16168377
2014 The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity 312 25526307
2008 Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508. Molecular biology of the cell 193 18216283
2006 The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site. Proceedings of the National Academy of Sciences of the United States of America 179 16407162
2004 AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation. The Journal of biological chemistry 177 15331598
2013 Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Molecular biology of the cell 172 23427266
2007 The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nature medicine 158 18037895
2009 Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Molecular cell 141 19560420
2011 Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8. Proceedings of the National Academy of Sciences of the United States of America 139 22143767
2006 Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. The Journal of biological chemistry 139 17043353
2012 Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis. Cell metabolism 119 22863805
2009 Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Human molecular genetics 117 19661182
2006 The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation. The Journal of biological chemistry 110 16987818
2021 The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis. Immunity 102 34407391
2003 Overexpression of the tumor autocrine motility factor receptor Gp78, a ubiquitin protein ligase, results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in HepG2 cells. The Journal of biological chemistry 100 12670940
2018 The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1. eLife 92 30543180
2011 Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The Journal of biological chemistry 83 21343306
2007 Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase. Cell metabolism 81 17681147
2014 MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1. Protein & cell 75 25149074
2009 The complex biology of autocrine motility factor/phosphoglucose isomerase (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase. Molecular bioSystems 71 19603112
2010 Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP. PloS one 70 20126661
2014 USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation. eLife 67 24424410
2015 Deacetylation of HSPA5 by HDAC6 leads to GP78-mediated HSPA5 ubiquitination at K447 and suppresses metastasis of breast cancer. Oncogene 64 26119938
2009 The E3 ubiquitin ligases Hrd1 and gp78 bind to and promote cholera toxin retro-translocation. Molecular biology of the cell 63 19864457
2015 gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum. Molecular biology of the cell 59 26424800
2022 Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation. Cell death and differentiation 57 35110683
2009 Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1. The international journal of biochemistry & cell biology 56 19828134
2017 Gp78 E3 Ubiquitin Ligase: Essential Functions and Contributions in Proteostasis. Frontiers in cellular neuroscience 52 28890687
2016 Ubiquitin-mediated regulation of the E3 ligase GP78 by MGRN1 in trans affects mitochondrial homeostasis. Journal of cell science 51 26743086
2008 CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases. Archives of biochemistry and biophysics 49 19103148
2006 Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin. Biochemical and biophysical research communications 49 16979136
2009 Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum. Biochemical and biophysical research communications 48 19835843
2005 Expression of autocrine motility factor (AMF) and its receptor, AMFR, in human breast cancer. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 48 16204225
2015 Gp78, an E3 ubiquitin ligase acts as a gatekeeper suppressing nonalcoholic steatohepatitis (NASH) and liver cancer. PloS one 46 25789613
2015 p38 MAP kinase-dependent phosphorylation of the Gp78 E3 ubiquitin ligase controls ER-mitochondria association and mitochondria motility. Molecular biology of the cell 43 26337390
2022 AMFR drives allergic asthma development by promoting alveolar macrophage-derived GM-CSF production. The Journal of experimental medicine 41 35333296
2014 Regulation of diacylglycerol acyltransferase 2 protein stability by gp78-associated endoplasmic-reticulum-associated degradation. The FEBS journal 41 24820123
2003 amfR, an essential gene for aerial mycelium formation, is a member of the AdpA regulon in the A-factor regulatory cascade in Streptomyces griseus. Molecular microbiology 40 14622407
2013 Regulation of mitochondrial antiviral signaling (MAVS) expression and signaling by the mitochondria-associated endoplasmic reticulum membrane (MAM) protein Gp78. The Journal of biological chemistry 39 24285545
2020 RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 -a dual organellar turnover mechanism. Autophagy 38 32559118
2014 Ube2g2-gp78-mediated HERP polyubiquitylation is involved in ER stress recovery. Journal of cell science 37 24496447
2017 Calcium sensing receptor protects high glucose-induced energy metabolism disorder via blocking gp78-ubiquitin proteasome pathway. Cell death & disease 35 28518143
2017 Role of HSPA1L as a cellular prion protein stabilizer in tumor progression via HIF-1α/GP78 axis. Oncogene 35 28759037
1997 The AMF-R tubule is a smooth ilimaquinone-sensitive subdomain of the endoplasmic reticulum. Journal of cell science 35 9365274
2023 Gp78 deficiency in hepatocytes alleviates hepatic ischemia-reperfusion injury via suppressing ACSL4-mediated ferroptosis. Cell death & disease 33 38065978
2018 Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR). Frontiers in pharmacology 33 29867487
2012 gp78: a multifaceted ubiquitin ligase that integrates a unique protein degradation pathway from the endoplasmic reticulum. Current protein & peptide science 33 22812524
2011 Multisite phosphorylation of human liver cytochrome P450 3A4 enhances Its gp78- and CHIP-mediated ubiquitination: a pivotal role of its Ser-478 residue in the gp78-catalyzed reaction. Molecular & cellular proteomics : MCP 32 22101235
2022 iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance. Proceedings of the National Academy of Sciences of the United States of America 30 35121659
2010 Liver cytochrome P450 3A ubiquitination in vivo by gp78/autocrine motility factor receptor and C terminus of Hsp70-interacting protein (CHIP) E3 ubiquitin ligases: physiological and pharmacological relevance. The Journal of biological chemistry 30 20819951
2002 A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78. Journal of neurochemistry 29 11902125
2023 Staphylococcal virulence factor HlgB targets the endoplasmic-reticulum-resident E3 ubiquitin ligase AMFR to promote pneumonia. Nature microbiology 27 36593296
2010 A role for KAI1 in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase. The Journal of biological chemistry 27 20089858
2017 Conformational Dynamics and Allostery in E2:E3 Interactions Drive Ubiquitination: gp78 and Ube2g2. Structure (London, England : 1993) 26 28434917
2014 Human liver cytochrome P450 3A4 ubiquitination: molecular recognition by UBC7-gp78 autocrine motility factor receptor and UbcH5a-CHIP-Hsc70-Hsp40 E2-E3 ubiquitin ligase complexes. The Journal of biological chemistry 26 25451919
2017 CDK5-Mediated Phosphorylation-Dependent Ubiquitination and Degradation of E3 Ubiquitin Ligases GP78 Accelerates Neuronal Death in Parkinson's Disease. Molecular neurobiology 25 28528366
2012 RING finger palmitoylation of the endoplasmic reticulum Gp78 E3 ubiquitin ligase. FEBS letters 25 22728137
1998 Characterization of an A-factor-responsive repressor for amfR essential for onset of aerial mycelium formation in Streptomyces griseus. Journal of bacteriology 25 9748440
2024 AMFR-mediated Flavivirus NS2A ubiquitination subverts ER-phagy to augment viral pathogenicity. Nature communications 23 39505910
2020 Spermine Protects Cardiomyocytes from High Glucose-Induced Energy Disturbance by Targeting the CaSR-gp78-Ubiquitin Proteasome System. Cardiovascular drugs and therapy 23 32918657
2005 Giant cell tumors of the bone: molecular profiling and expression analysis of Ephrin A1 receptor, Claudin 7, CD52, FGFR3 and AMFR. Pathology, research and practice 23 16325507
2003 Cloning of the conserved regulatory operon by its aerial mycelium-inducing activity in an amfR mutant of Streptomyces griseus. Gene 23 12657469
2022 Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS. Cellular and molecular life sciences : CMLS 22 36284011
2003 Overexpression of autocrine motility factor receptor (AMFR) in NIH3T3 fibroblasts induces cell transformation. Clinical & experimental metastasis 22 12650607
2014 Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget 21 24810856
2004 The gene product of the gp78/AMFR ubiquitin E3 ligase cDNA is selectively recognized by the 3F3A antibody within a subdomain of the endoplasmic reticulum. Biochemical and biophysical research communications 20 15303277
2023 AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model. Acta neuropathologica 19 37119330
2013 Raft endocytosis of AMF regulates mitochondrial dynamics through Rac1 signaling and the Gp78 ubiquitin ligase. Journal of cell science 19 23690547
2022 Acacetin protects against depression-associated dry eye disease by regulating ubiquitination of NLRP3 through gp78 signal. Frontiers in pharmacology 16 36299901
2017 Neuroprotective effect of (-)-tetrahydropalmatine in Japanese encephalitis virus strain GP-78 infected mouse model. Microbial pathogenesis 16 29191708
2014 The E3 ubiquitin ligase gp78 protects against ER stress in zebrafish liver. Journal of genetics and genomics = Yi chuan xue bao 15 25064675
2014 Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. PloS one 14 24714645
2019 GP78 Cooperates with Dual-Specificity Phosphatase 1 To Stimulate Epidermal Growth Factor Receptor-Mediated Extracellular Signal-Regulated Kinase Signaling. Molecular and cellular biology 13 31061093
2019 Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance. Molecular pharmacology 13 31492698
2015 Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients. Proteomics. Clinical applications 13 25689831
2024 Impaired STING Activation Due to a Variant in the E3 Ubiquitin Ligase AMFR in a Patient with Severe VZV Infection and Hemophagocytic Lymphohistiocytosis. Journal of clinical immunology 12 38277122
2014 gp78 elongates of polyubiquitin chains from the distal end through the cooperation of its G2BR and CUE domains. Scientific reports 12 25409783
2011 CHIP and gp78-mediated ubiquitination of CYP3A4: Implications for the pharmacology of anticancer agents. Cancer biology & therapy 12 21270532
2022 Pharmacological induction of AMFR increases functional EAAT2 oligomer levels and reduces epileptic seizures in mice. JCI insight 11 35938532
2018 Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 30230921
2017 SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78. PloS one 10 28301499
2022 The GR-gp78 Pathway is involved in Hepatic Lipid Accumulation Induced by Overexpression of 11β-HSD1. International journal of biological sciences 9 35637957
2006 AMF/G6PI induces differentiation of leukemic cells via an unknown receptor that differs from gp78. Leukemia & lymphoma 9 17071500
1997 AMF-R tubules concentrate in a pericentriolar microtubule domain after MSV transformation of epithelial MDCK cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 8 9313797
2014 A novel polymorphism of the GP78 gene is associated with coronary artery disease in Han population in China. Lipids in health and disease 7 25200441
2011 The Gp78 ubiquitin ligase: probing endoplasmic reticulum complexity. Protoplasma 7 22045301
2024 Cholesterol suppresses AMFR-mediated PDL1 ubiquitination and degradation in HCC. Molecular and cellular biochemistry 5 39231894
2022 Expression of autocrine motility factor receptor (AMFR) in human breast and lung invasive micropapillary carcinomas. International journal of experimental pathology 5 36576071
2018 The ubiquitin specific protease USP34 protects the ubiquitin ligase gp78 from proteasomal degradation. Biochemical and biophysical research communications 5 30585151
2025 ER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40673870
2024 gp78-regulated KAP1 phosphorylation induces radioresistance in breast cancer by facilitating PPP1CC/PPP2CA ubiquitination. iScience 4 39297166
2017 Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease. Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese 4 28212872
2016 AMFR gene silencing inhibits the differentiation of porcine preadipocytes. Genetics and molecular research : GMR 4 27173213
2013 gp78 is specifically expressed in human prostate cancer rather than normal prostate tissue. Journal of molecular histology 4 23666464
2003 Peripherally located occult lung cancer with AMFR expression. Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 4 12875641
2022 AMFR and DCTN2 genes cause transplantation resistance of adipose-derived mesenchymal stem cells in type 1 diabetes mellitus. Frontiers in pharmacology 3 36267277
2025 Immunohistochemical markers of potential utility in identifying POLE-mutant endometrial carcinomas: An assessment of autocrine motility factor (AMF) and autocrine motility factor receptor (AMFR). Annals of diagnostic pathology 1 39787898
2023 AMFR promotes innate immunity activation and proteasomal degradation of HMGCR in response to influenza virus infection in A549 cells. Virology 1 37703797
2019 Expression of Gp78/Autocrine Motility Factor Receptor and Endocytosis of Autocrine Motility Factor in Human Thyroid Cancer Cells. Cureus 1 31431834

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