Affinage

FAF1

FAS-associated factor 1 · UniProt Q9UNN5

Length
650 aa
Mass
74.0 kDa
Annotated
2026-06-09
60 papers in source corpus 35 papers cited in narrative 35 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

FAF1 is a multi-domain scaffold protein that integrates apoptotic signaling, ubiquitin-dependent protein extraction, and lipid sequestration to govern cell death and proteostasis (PMID:12702723, PMID:23293021, PMID:35467977). It was first defined as a Fas-associated protein that binds the cytoplasmic domain of wild-type Fas and potentiates Fas-induced apoptosis (PMID:8524870), and it operates within the Fas-DISC by associating with FADD and caspase-8 through their death-effector domains, placing it upstream of caspase-8 activation (PMID:12702723). In parallel, FAF1 acts as a UBX-domain cofactor of the p97/VCP-Ufd1-Npl4 segregase: its N-terminal UBA domain recognizes K48-linked polyubiquitin while its C-terminal UBX domain docks onto p97, and a helix anchored by the p97-bound UBX domain braces the Ufd1 UT3 domain to accelerate substrate unfolding and proteasomal degradation (PMID:23293021, PMID:42228561, PMID:41790892). Through this VCP-coupling activity FAF1 drives ERAD and the chromatin extraction of ubiquitylated and SUMOylated replication factors such as CDT-1, promoting replication-fork progression and genome stability, an activity that cooperates with USP7-mediated deubiquitylation (PMID:26842564, PMID:34644576). FAF1 suppresses NF-κB by binding IKKβ through its leucine-zipper and disrupting IKK complex assembly (PMID:17684021), and antagonizes innate antiviral immunity by competing with TRIM31 for MAVS, a suppressive function relieved by IKKε phosphorylation at Ser556 that triggers FAF1 lysosomal degradation (PMID:30472208). Its UAS domain sequesters free polyunsaturated fatty acids into a hydrophobic core, protecting cells from ferroptosis upstream of GPX4 (PMID:35467977). FAF1 abundance and activity are tuned by post-translational control: parkin ubiquitinates FAF1 to limit its pro-death role in dopaminergic neurons (PMID:23307929), and AKT phosphorylation at Ser582 disrupts the FAF1-VCP complex to stabilize the TGF-β type II receptor and enhance TGF-β signaling (PMID:28443643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Established FAF1 as a physical partner of the Fas death receptor and a potentiator of apoptosis, defining its founding role in death-receptor signaling.

    Evidence Yeast two-hybrid against the Fas cytoplasmic domain, co-IP, and transient overexpression apoptosis assay in L cells

    PMID:8524870

    Open questions at the time
    • Did not define the molecular step at which FAF1 acts in the apoptotic cascade
    • Did not map the FAF1 domains responsible for Fas binding
  2. 1999 Medium

    Mapped the Fas-binding activity of human FAF1 to its N-terminal ubiquitin-homology-containing region, localizing the interaction surface.

    Evidence GST pulldown with in vitro translated Fas and cDNA cloning

    PMID:10462485

    Open questions at the time
    • Pulldown-level evidence without functional consequence
    • Did not address whether N-terminal binding is required for apoptosis
  3. 2001 Medium

    Distinguished an intrinsic, Fas-independent apoptotic activity residing in the ubiquitin-homology domain, and identified CK2 as the major FAF1 kinase.

    Evidence Deletion-mutant overexpression with apoptosis readouts; in vitro CK2 kinase assay with MS site mapping (Ser289/Ser291)

    PMID:11378439 PMID:11527403

    Open questions at the time
    • Functional role of CK2 phosphorylation not yet linked to apoptosis
    • Mechanism of the Fas-independent death activity unresolved
  4. 2003 High

    Resolved FAF1's position in the Fas-DISC upstream of caspase-8 and showed CK2 phosphorylation controls its nuclear import rather than its apoptotic potency.

    Evidence Reciprocal co-IP, confocal localization, dominant-negative and genetic epistasis in FADD/caspase-8-deficient Jurkat cells; in vivo phosphorylation and nuclear import assays

    PMID:12702723 PMID:12832043

    Open questions at the time
    • Stoichiometry of FAF1 within the assembled DISC not defined
    • How nuclear import relates to FAF1's cytoplasmic death function unclear
  5. 2007 High

    Defined FAF1 as a negative regulator of NF-κB acting by disrupting IKK complex assembly, extending its role from apoptosis into inflammatory signaling.

    Evidence Reciprocal co-IP, siRNA knockdown and overexpression with IKK kinase activity assays

    PMID:17684021

    Open questions at the time
    • Whether IKK regulation is stimulus-specific not fully resolved
    • Structural basis of leucine-zipper-mediated IKKβ binding undefined
  6. 2013 High

    Established the bipartite ubiquitin/p97-binding architecture of FAF1 as a VCP cofactor driving ERAD, and placed parkin as the E3 ligase restraining its pro-death activity in dopaminergic neurons.

    Evidence Co-IP and biochemical analysis of UBA/UBX binding with ERAD assays; in vitro and cell-based ubiquitination plus FAF1-deficient/MPTP mouse models; UAS-domain PUFA polymerization assays

    PMID:23293021 PMID:23307929 PMID:23720822

    Open questions at the time
    • Functional consequence of UAS-domain fatty-acid polymerization not yet defined
    • How parkin loss and FAF1 accumulation drive neurodegeneration mechanistically unclear
  7. 2014 High

    Defined the structural stoichiometry and accessory interactions of the FAF1-p97 segregase module, including bridging VAPB to p97.

    Evidence Cryo-EM, native MS and analytical ultracentrifugation of p97-FAF1; FFAT-motif binding to VAPB MSP domain with siRNA knockdown

    PMID:24619421 PMID:24885147

    Open questions at the time
    • Functional output of VAPB bridging to ubiquitinated proteins not fully resolved
    • How FAF1 stoichiometry on p97 tunes substrate processing unknown
  8. 2016 High

    Identified FAF1/UBXN-3 as the p97 adaptor that extracts CDT-1 and other ubiquitylated replication factors from chromatin to safeguard fork progression, and uncovered a stress-induced nuclear PARP1-activating necrotic function.

    Evidence Cross-species genetic depletion (C. elegans/human), chromatin fractionation and fork dynamics; subcellular fractionation, co-IP, siRNA and in vivo midbrain overexpression for PARP1 axis

    PMID:26842564 PMID:27662363

    Open questions at the time
    • How FAF1 selects replication-factor substrates not defined
    • Switch between PARP1-necrotic and proteostatic functions of nuclear FAF1 unclear
  9. 2017 High

    Connected FAF1 to growth-factor and stress signaling through AKT phosphorylation-controlled VCP recruitment regulating TβRII, and through JNK1-dependent ischemic cell death.

    Evidence Co-IP, in vitro AKT kinase assay, FAF1 KO and MMTV-PyMT mouse models; conditional retinal KO with JNK1 activity readouts

    PMID:28443643 PMID:30200976

    Open questions at the time
    • Whether Ser582 phosphorylation regulates VCP functions beyond TβRII unknown
    • Direct vs. indirect basis of FAF1-JNK1 coupling not resolved
  10. 2018 High

    Established FAF1 as a brake on antiviral innate immunity through aggregation-dependent competition with TRIM31 at MAVS, relieved by IKKε phosphorylation-triggered lysosomal degradation.

    Evidence Co-IP, in vitro IKKε kinase assay, ubiquitination assays and FAF1 KO mice in viral infection models

    PMID:30472208

    Open questions at the time
    • Structural basis of FAF1 aggregate competition with TRIM31 undefined
    • How Ser556 phosphorylation drives de-aggregation mechanistically unclear
  11. 2021 High

    Revealed that FAF1-VCP extracts SUMOylated as well as ubiquitylated replication proteins and functionally cooperates with USP7 deubiquitylation at forks, exposing a synthetic-lethal vulnerability.

    Evidence Double-KO/KD epistasis and pharmacological synergy in C. elegans and mammalian cells with chromatin fractionation

    PMID:34644576

    Open questions at the time
    • Mechanism coupling SUMO recognition to extraction not defined
    • Therapeutic window of USP7/VCP synergy untested clinically
  12. 2022 High

    Defined a non-enzymatic ferroptosis-protective mechanism in which FAF1 sequesters free PUFAs into a hydrophobic core, acting upstream of GPX4.

    Evidence FAF1 KO cells and mice, ferroptosis and lipid-peroxidation assays, structural biochemistry of globular PUFA-sequestering assembly

    PMID:35467977

    Open questions at the time
    • Regulation of FAF1 PUFA sequestration in vivo not defined
    • Relationship between lipid-binding and proteostatic functions unresolved
  13. 2026 High

    Provided the mechanistic basis for FAF1's stimulation of p97-driven proteolysis, showing its UBX-anchored helix braces the Ufd1 UT3 domain to accelerate K48-ubiquitin unfolding.

    Evidence In vitro reconstitution with human components, FRET assays, cryo-EM and mutagenesis (independently replicated)

    PMID:41790892 PMID:42228561

    Open questions at the time
    • How this acceleration is regulated by FAF1 phosphorylation not addressed
    • Substrate-specificity determinants of the accelerated unfolding undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FAF1's distinct activities—DISC scaffolding, p97-segregase cofactor function, lipid sequestration, and signaling regulation—are coordinately switched within a single cell remains unresolved.
  • No integrated model linking phosphorylation state to choice among FAF1 functions
  • Unclear how domain-specific activities are spatially partitioned across nucleus, cytosol, ER and plasma membrane

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-69306 DNA Replication 2
Partners
CASP8CDT1FADDFASIKBKBMAVSVAPBVCP
Complex memberships
Fas-DISCp97/VCP-Ufd1-Npl4 complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 FAF1 was identified as a protein that specifically interacts with the cytoplasmic domain of wild-type Fas but not the lprcg-mutated Fas, and potentiates Fas-induced apoptosis when transiently expressed in L cells. Yeast two-hybrid screen, mammalian co-immunoprecipitation, transient overexpression with apoptosis readout Proceedings of the National Academy of Sciences of the United States of America High 8524870
2003 FAF1 is a member of the Fas-DISC, interacting with FADD and caspase-8 via their death effector domains (DEDs) binding the amino acid 181-381 region of FAF1. FAF1 colocalizes with Fas at the cytoplasmic membrane before Fas activation and moves to the cytoplasm after activation. A dominant-negative FAF1 deletion mutant lacking the N-terminus protects cells from Fas-induced apoptosis, and FAF1-mediated cell death is suppressed in FADD- and caspase-8-deficient cells, placing FAF1 upstream of caspase-8. Co-immunoprecipitation (in vivo and in vitro), confocal microscopy, dominant-negative overexpression, genetic epistasis in FADD/caspase-8-deficient Jurkat cells The Journal of biological chemistry High 12702723
1999 Human FAF1 (hFAF1) was identified and characterized; the N-terminal region (amino acids 1–201) including the upstream ubiquitin homology domain binds to the death domain of Fas but not to the lprcg mutant Fas. GST pulldown with in vitro translation product of Fas, cDNA cloning Biochemical and biophysical research communications Medium 10462485
2001 Apoptosis induced by hFAF1 overexpression requires its ubiquitin homologous domain (UB2) and adjacent nuclear localization signal, but not the Fas-binding domain, indicating an intrinsic apoptotic activity independent of Fas binding. Transient overexpression of deletion mutants, apoptosis assays (membrane blebbing, phosphatidylserine exposure, caspase-3 activation) Biochemical and biophysical research communications Medium 11527403
2001 Protein kinase CK2 phosphorylates FAF1 in vitro at Ser289 and Ser291, and CK2 is the major cellular kinase responsible for FAF1 phosphorylation in cell extracts. In vitro kinase assay with recombinant CK2, MALDI-MS identification of phosphorylation sites, tissue extract kinase assay The international journal of biochemistry & cell biology High 11378439
2003 CK2 phosphorylates FAF1 at Ser289 and Ser291 in vivo (at least one site confirmed), and phosphorylation-deficient FAF1 mutants show delayed nuclear import compared to wild-type FAF1, without affecting FAF1's ability to potentiate Fas-induced apoptosis. In vivo phosphorylation analysis, nuclear import assay with phosphorylation-deficient mutants FEBS letters Medium 12832043
2004 FAF1 selectively coactivates mineralocorticoid receptor (MR)-mediated transcription but does not transactivate glucocorticoid receptor (GR), as shown by yeast two-hybrid interaction and transient transactivation assays in mouse hippocampal cells. Yeast two-hybrid screen, transient transactivation assays in mammalian neural cells Molecular pharmacology Medium 14978255
2007 FAF1 suppresses IKK activation by interacting with IKKβ via its leucine-zipper domain, disrupting IKK heterocomplex and homocomplex formation and attenuating IKKγ recruitment to IKKβ, thereby inhibiting NF-κB signaling in response to TNF-α, IL-1β, and LPS. Co-immunoprecipitation, overexpression and siRNA knockdown with IKK kinase activity assays The Journal of biological chemistry High 17684021
2013 FAF1 interacts with VCP complexed with Npl4-Ufd1 heterodimer via its C-terminal UBX domain, and with polyubiquitinated proteins via its N-terminal UBA domain (which recognizes Lys48-linked ubiquitin), promoting endoplasmic reticulum-associated degradation (ERAD). VCP association to the UBX domain regulates ubiquitin binding to the UBA domain. Co-immunoprecipitation, structural and biochemical analysis, ERAD functional assays The Journal of biological chemistry High 23293021
2011 Crystal structure of human FAF1 UBX domain at 2.9 Å resolution reveals a conserved FcisP touch-turn motif in the p97/VCP-binding region, with two conformations of this motif suggesting a conformational change upon binding to p97/VCP N domain. X-ray crystallography Biochemical and biophysical research communications High 21414298
2014 FAF1 binds p97 stably in a stoichiometry of 3–6 FAF1 per p97 hexamer; cryo-EM reconstruction at 17 Å shows FAF1 positioned above the p97 ring. Cryo-EM, native mass spectrometry, analytical ultracentrifugation The Journal of biological chemistry High 24619421
2013 Parkin acts as an E3 ubiquitin ligase that ubiquitinates FAF1 both in vitro and in cells; PD-linked parkin mutations disrupt FAF1 ubiquitination and degradation, elevating FAF1 expression. Wild-type parkin abolishes FAF1-mediated cell death, but PD-linked mutants do not. FAF1 accumulates in the substantia nigra in MPTP-treated mice, and FAF1-deficient mice show attenuated MPTP-induced dopaminergic cell loss. In vitro ubiquitination assay, cell-based ubiquitination assay, mouse model (gene trap and MPTP treatment), behavioral and biochemical readouts Human molecular genetics High 23307929
2013 The UAS domain of FAF1 polymerizes upon interaction with long-chain unsaturated fatty acids; specific mutations in positively charged surface residues of the UAS domain prevent this polymerization. In vitro polymerization assay, site-directed mutagenesis, cell-based fatty acid regulation assay Journal of lipid research High 23720822
2014 FAF1 contains a non-canonical FFAT motif that allows direct interaction with the MSP domain of VAPB, thereby mediating VAPB interaction with p97. FAF1 knockdown strongly reduces VAPB interaction with ubiquitinated proteins. Co-immunoprecipitation, direct binding assays, siRNA knockdown BMC biology Medium 24885147
2016 FAF1/UBXN-3 binds to the licensing factor CDT-1 and ubiquitylated proteins to promote CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes at the fork. Inactivation of FAF1/UBXN-3 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing replication fork defects, replication stress, and genome instability. Genetic knockdown/knockout in C. elegans and human cells, chromatin fractionation, replication fork dynamics assays Nature communications High 26842564
2016 Upon oxidative stress, FAF1 translocates from the cytoplasm to the nucleus and promotes catalytic activation of PARP1 through direct physical interaction, driving PARP1-dependent necrotic cell death (energetic collapse, mitochondrial depolarization, AIF nuclear translocation). FAF1 overexpression in mouse ventral midbrain promotes PARP1 activation and dopaminergic neurodegeneration in the MPTP model. Subcellular fractionation and immunofluorescence, co-immunoprecipitation, siRNA knockdown with cell death assays, AAV-mediated overexpression in mouse brain Cell death and differentiation High 27662363
2017 FAF1 destabilizes TGF-β type II receptor (TβRII) on the cell surface by recruiting the VCP/E3 ligase complex. AKT directly phosphorylates FAF1 at Ser582, disrupting the FAF1-VCP complex and reducing FAF1 at the plasma membrane, resulting in increased TβRII surface levels and enhanced TGF-β signaling. Co-immunoprecipitation, in vitro kinase assay, FAF1 knockout mouse model, EMT and metastasis assays, MMTV-PyMT transgenic mouse model Nature communications High 28443643
2018 FAF1 forms aggregates that negatively regulate MAVS by competing with TRIM31 for MAVS association, thereby antagonizing K63-linked polyubiquitination and aggregation of MAVS. Upon viral infection, IKKε directly phosphorylates FAF1 at Ser556, triggering FAF1 de-aggregation and lysosomal degradation, relieving FAF1-dependent suppression of MAVS. FAF1 knockout mice show enhanced innate antiviral signaling and reduced viral load. Co-immunoprecipitation, in vitro kinase assay, FAF1 knockout mice, viral infection models, ubiquitination assays Cell host & microbe High 30472208
2019 FAF1 contains two SUMO-interacting motifs (SIMs) that are crucial for interaction with sumoylated mineralocorticoid receptor (MR) and for repressing aldosterone-activated MR transactivation. FAF1/SIM-mediated MR repression involves inhibition of MR N/C interactions and promotion of MR polyubiquitination and degradation. Silencing FAF1 increases aldosterone-induced MR target gene expression. Mutagenesis of SIM motifs, co-immunoprecipitation, transactivation reporter assays, siRNA knockdown Biochimica et biophysica acta. Molecular cell research Medium 30935967
2020 FAF1 missense variants (p.Asp371Asn and p.Arg85Pro) encode unstable FAF1 proteins; expression of these variants in CRC cells causes resistance to apoptosis, accumulation of β-catenin in the cytoplasm, and NF-κB nuclear translocation, establishing FAF1 as a functional regulator of both apoptosis and Wnt/NF-κB pathways. CRISPR/Cas9 gene editing, transfection of missense variants, apoptosis assays, Western blot, NF-κB and Wnt reporter assays Gastroenterology Medium 32179092
2021 VCP/FAF1 facilitates extraction of SUMOylated and ubiquitylated DNA replication proteins from chromatin. FAF1 inactivation combined with USP7 inactivation is synthetically lethal in C. elegans and mammalian cells, and USP7/VCP inhibitors show synergistic toxicity, establishing a functional cooperation between FAF1-dependent chromatin extraction and USP7-mediated deubiquitylation at replication forks. Genetic epistasis (double KO/KD), chromatin fractionation, proteasome inhibitor treatment, pharmacological synergy assays in C. elegans and mammalian cells Cell reports High 34644576
2022 FAF1 assembles a globular structure that sequesters free polyunsaturated fatty acids (PUFAs) into a hydrophobic core via its UAS domain interaction, preventing PUFA peroxidation by limiting iron access. FAF1 knockout mice develop hepatic injury on PUFA-enriched diet, and FAF1-deficient cells become sensitive to ferroptosis upon PUFA exposure, placing FAF1 upstream of GPX4 in ferroptosis protection. FAF1 knockout cell lines and mice, ferroptosis assays, structural biochemistry (globular assembly), lipid peroxidation assays Proceedings of the National Academy of Sciences of the United States of America High 35467977
2014 FAF1 interacts with CD40 via its N-terminal FID domain, binding to the TRAF6-binding domain of CD40's cytoplasmic tail. CD40 ligation induces FAF1 expression in an NF-κB-dependent manner, and FAF1 in turn suppresses CD40-induced NF-κB activation via a negative feedback loop; FAF1 knockdown prolongs CD40-induced NF-κB activation. Yeast two-hybrid, in vitro and in vivo co-immunoprecipitation, siRNA knockdown, NF-κB reporter assays Cell death & disease Medium 24810049
2015 HSP70 interacts with FAF1 via its N-terminal 1–120 amino acid sequence and competitively inhibits FAF1 binding to Fas, suppressing caspase-8 activation and apoptosis. An N-terminal HSP70 deletion mutant (HSP70-ΔN) cannot interact with FAF1 and fails to attenuate stress-induced apoptosis. Co-immunoprecipitation, competitive binding assays, overexpression of domain deletion mutants, caspase activity assays Cell stress & chaperones Medium 25935138
2017 XIAP interacts with FAF1, promotes ubiquitination of FAF1, blocks FAF1-mediated cell death by interfering with the caspase cascade, and directly interferes with FAF1's inhibition of NF-κB. Conversely, FAF1 attenuates XIAP-mediated NF-κB activation without affecting XIAP's anti-apoptotic activity. Co-immunoprecipitation, domain mapping, ubiquitination assay, cell death assays, NF-κB reporter assays Biochimica et biophysica acta. Molecular cell research Medium 28414080
2018 FAF1 functions upstream of JNK1 upon ischemic insult; FAF1 physically interacts with JNK1 and promotes JNK1-mediated mitochondrial dysfunction and necrotic cell death. Conditional FAF1 knockout in retinal cells (Dkk3-Cre;Faf1flox/flox mice) attenuates JNK1 activation and ameliorates ischemic retinal cell death. Immunoprecipitation, conditional KO mouse model, retinal ischemia model with IOP elevation, JNK1 activity assays Cell communication and signaling High 30200976
2020 FAF1 is secreted from neuronal cells via both BFA-resistant secretory pathways (vesicle-free form) and as exosome cargo. Extracellular FAF1 is taken up by neighboring cells via endocytosis and induces cell death through apoptotic and necrotic pathways. FAF1 also increases the number of exosomes, suggesting a regulatory role in exosome biogenesis. Conditioned medium analysis, ultracentrifugation exosome isolation, electron microscopy, nanoparticle tracking analysis, transwell transmission assay, flow cytometry Cell communication and signaling Medium 32831099
2024 VCP controls ubiquitin-proteasomal degradation of KCC2 dependent on FAF1 recruitment; propofol-induced degradation of KCC2 is inhibited by FAF1 knockout, demonstrating that FAF1 is required for VCP-mediated targeting of ubiquitinated KCC2 to the proteasome. VCP inhibitor (DBeQ), VCP and FAF1 knockout (sgRNA), co-immunoprecipitation, in vivo VPM microinjection in mice Proceedings of the National Academy of Sciences of the United States of America Medium 39793039
2024 SAP130 sumoylation at Lys794, Lys878, and Lys932 is required for its interaction with FAF1; FAF1 promotes SAP130 polyubiquitination and degradation in a sumoylation-dependent manner, thereby counteracting SAP130's transcriptional repression activity. In vitro and in vivo sumoylation assays, mutagenesis of SUMO acceptor sites, co-immunoprecipitation, polyubiquitination assay, transcriptional reporter assays BMC molecular and cell biology Medium 38172660
2025 Extracellular GMFB activates FAF1 via the FAS receptor to promote degradation of the H+-ATPase ATP6V1A, leading to lysosomal dysfunction in retinal pigment epithelial cells. FAS siRNA and antagonist partially reverse GMFB-induced lysosomal damage, establishing a FAS-FAF1-ATP6V1A signaling axis. siRNA library screening, immunofluorescence, molecular docking, co-immunoprecipitation, intravitreal injection in vivo International journal of biological macromolecules Medium 40490177
2026 FAF1 accelerates p97/VCP-mediated unfolding of K48-ubiquitinated substrates by using its p97-bound C-terminal UBX domain to anchor a long helix that braces the UT3 domain of Ufd1, stabilizing the Ufd1-Npl4 cofactor for ubiquitin unfolding and engagement by the ATPase motor. This mechanism stimulates proteasomal degradation. In vitro reconstituted unfolding system with human components, FRET-based assays, cryo-EM structure determination, mutagenesis Cell reports High 41790892 42228561
2017 FAF1 regulates CD40-induced NF-κB activation via a negative feedback loop: CD40 ligation induces FAF1 expression in an NF-κB-dependent manner, and FAF1 in turn suppresses CD40-induced NF-κB activation through interaction with CD40 via its FID domain. (Note: this finding overlaps with PMID:24810049 above and is the same discovery.) Yeast two-hybrid, Co-IP, NF-κB reporter, siRNA knockdown Cell death & disease Medium 24810049
2011 FAF1 expression is required for cranial neural crest (CNC) differentiation in zebrafish; faf1 knockdown causes pharyngeal cartilage defects and jaw abnormality due to failure of CNC to differentiate and express cartilage markers sox9a and col2a1. Rescue with faf1 mRNA restores the phenotype. Zebrafish morpholino knockdown, mRNA rescue, in situ hybridization for cartilage markers American journal of human genetics Medium 21295280
2017 FAF1 impairs autophagic flux in dopaminergic neurons, leading to α-synuclein accumulation; pharmacological targeting of FAF1 with KM-819 restores autophagic flux and reduces α-synuclein accumulation in FAF1-overexpressing neuronal cells and in A53T α-synuclein transgenic mice. FAF1 overexpression via AAV, pharmacological inhibition (KM-819), autophagic flux assays, α-synuclein quantification, transgenic mouse model ACS chemical neuroscience Medium 35230076
2017 NLRP2 protein physically interacts with FAF1 in mouse oocytes and preimplantation embryos; knockdown of either Nlrp2 or Faf1 interferes with NLRP2-FAF1 complex formation and causes developmental arrest in early embryogenesis. Co-immunoprecipitation from oocytes and embryos, immunofluorescence colocalization, zygote knockdown Reproduction (Cambridge, England) Medium 28630100

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PloS one 198 20195546
1995 A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proceedings of the National Academy of Sciences of the United States of America 167 8524870
2003 Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex. The Journal of biological chemistry 89 12702723
2009 FAS-associated factor 1 (FAF1): diverse functions and implications for oncogenesis. Cell cycle (Georgetown, Tex.) 81 19597341
2019 Ammonia regulates chicken tracheal cell necroptosis via the LncRNA-107053293/MiR-148a-3p/FAF1 axis. Journal of hazardous materials 77 31791863
2004 DAXX, FLASH, and FAF-1 modulate mineralocorticoid and glucocorticoid receptor-mediated transcription in hippocampal cells--toward a basis for the opposite actions elicited by two nuclear receptors? Molecular pharmacology 72 14978255
2021 6-Gingerol protects against cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome and apoptosis via TRPV1 / FAF1 complex dissociation-mediated autophagy. International immunopharmacology 59 34537481
2013 Complex of Fas-associated factor 1 (FAF1) with valosin-containing protein (VCP)-Npl4-Ufd1 and polyubiquitinated proteins promotes endoplasmic reticulum-associated degradation (ERAD). The Journal of biological chemistry 53 23293021
2011 FAF1, a gene that is disrupted in cleft palate and has conserved function in zebrafish. American journal of human genetics 51 21295280
2007 FAF1 suppresses IkappaB kinase (IKK) activation by disrupting the IKK complex assembly. The Journal of biological chemistry 51 17684021
2018 FAF1 Regulates Antiviral Immunity by Inhibiting MAVS but Is Antagonized by Phosphorylation upon Viral Infection. Cell host & microbe 47 30472208
2017 FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis. Nature communications 46 28443643
1999 Identification and characterization of human Fas associated factor 1, hFAF1. Biochemical and biophysical research communications 46 10462485
2001 Apoptosis induced by human Fas-associated factor 1, hFAF1, requires its ubiquitin homologous domain, but not the Fas-binding domain. Biochemical and biophysical research communications 43 11527403
2013 Accumulation of the parkin substrate, FAF1, plays a key role in the dopaminergic neurodegeneration. Human molecular genetics 40 23307929
2016 Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. Nature communications 38 26842564
2013 UAS domain of Ubxd8 and FAF1 polymerizes upon interaction with long-chain unsaturated fatty acids. Journal of lipid research 38 23720822
2022 FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids. Proceedings of the National Academy of Sciences of the United States of America 35 35467977
2016 FAF1 mediates regulated necrosis through PARP1 activation upon oxidative stress leading to dopaminergic neurodegeneration. Cell death and differentiation 33 27662363
2014 VAPB/ALS8 interacts with FFAT-like proteins including the p97 cofactor FAF1 and the ASNA1 ATPase. BMC biology 31 24885147
2015 HSP70 inhibits stress-induced cardiomyocyte apoptosis by competitively binding to FAF1. Cell stress & chaperones 28 25935138
2001 Phosphorylation of the Fas associated factor FAF1 by protein kinase CK2 and identification of serines 289 and 291 as the in vitro phosphorylation sites. The international journal of biochemistry & cell biology 27 11378439
2022 Circ_0004354 might compete with circ_0040039 to induce NPCs death and inflammatory response by targeting miR-345-3p-FAF1/TP73 axis in intervertebral disc degeneration. Oxidative medicine and cellular longevity 26 35039758
2014 The p97-FAF1 protein complex reveals a common mode of p97 adaptor binding. The Journal of biological chemistry 25 24619421
2020 MiR-26a-5p Serves as an Oncogenic MicroRNA in Non-Small Cell Lung Cancer by Targeting FAF1. Cancer management and research 24 32848467
2017 Long non‑coding RNA FAF1 promotes intervertebral disc degeneration by targeting the Erk signaling pathway. Molecular medicine reports 24 29257270
2008 Fas-associated factor (FAF1) is required for the early cleavage-stages of mouse embryo. Molecular human reproduction 24 18303090
2020 Germline Mutations in FAF1 Are Associated With Hereditary Colorectal Cancer. Gastroenterology 22 32179092
2014 Interaction between ribosome assembly factors Krr1 and Faf1 is essential for formation of small ribosomal subunit in yeast. The Journal of biological chemistry 21 24990943
2012 KRT8, FAF1 and PTH1R gene polymorphisms are associated with leg weakness traits in pigs. Molecular biology reports 18 23196707
2021 USP7 and VCPFAF1 define the SUMO/Ubiquitin landscape at the DNA replication fork. Cell reports 17 34644576
2019 Identification of two independent SUMO-interacting motifs in Fas-associated factor 1 (FAF1): Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation. Biochimica et biophysica acta. Molecular cell research 16 30935967
2003 Protein kinase CK2 phosphorylates the Fas-associated factor FAF1 in vivo and influences its transport into the nucleus. FEBS letters 16 12832043
2011 Crystal structure of human FAF1 UBX domain reveals a novel FcisP touch-turn motif in p97/VCP-binding region. Biochemical and biophysical research communications 14 21414298
2008 Faf1 is expressed during neurodevelopment and is involved in Apaf1-dependent caspase-3 activation in proneural cells. Cellular and molecular life sciences : CMLS 13 18480964
2017 NLRP2 and FAF1 deficiency blocks early embryogenesis in the mouse. Reproduction (Cambridge, England) 12 28630100
2015 Identification of pathways related to FAF1/H. pylori-associated gastric carcinogenesis through an integrated approach based on iTRAQ quantification and literature review. Journal of proteomics 12 26597625
2020 A novel function of FAF1, which induces dopaminergic neuronal death through cell-to-cell transmission. Cell communication and signaling : CCS 11 32831099
2014 Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-κB activation via a negative feedback loop. Cell death & disease 11 24810049
2012 Reduced FAF1 Expression and Helicobacter Infection: Correlations with Clinicopathological Features in Gastric Cancer. Gastroenterology research and practice 9 23304123
2021 FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth. Journal of cellular and molecular medicine 7 34464509
2018 FAF1 mediates necrosis through JNK1-mediated mitochondrial dysfunction leading to retinal degeneration in the ganglion cell layer upon ischemic insult. Cell communication and signaling : CCS 7 30200976
2017 XIAP Interacts with and Regulates the Activity of FAF1. Biochimica et biophysica acta. Molecular cell research 6 28414080
2015 Molecular Analysis of a Recurrent Sarcoma Identifies a Mutation in FAF1. Sarcoma 6 25861239
2009 Crystallization and preliminary X-ray crystallographic analysis of the N domain of p97/VCP in complex with the UBX domain of FAF1. Acta crystallographica. Section F, Structural biology and crystallization communications 6 20057067
2024 Inhibition of circ_0073932 attenuates myocardial ischemia‒reperfusion injury via miR-493-3p/FAF1/JNK. In vitro cellular & developmental biology. Animal 5 38578382
2022 Pharmacological Intervention Targeting FAF1 Restores Autophagic Flux for α-Synuclein Degradation in the Brain of a Parkinson's Disease Mouse Model. ACS chemical neuroscience 5 35230076
2024 VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia. Proceedings of the National Academy of Sciences of the United States of America 4 39793039
2000 Human Fas associated factor 1, hFAF1, gene maps to chromosome band 1p32. Molecules and cells 4 11101154
2025 Extracellular GMFB activates the non-canonical FAS-FAF1 pathway to induce lysosomal dysfunction in early diabetic retinopathy. International journal of biological macromolecules 3 40490177
2021 Association analysis of SNPs in GRHL3, FAF1, and KCNJ2 with NSCPO sub-phenotypes in Han Chinese. Oral diseases 3 34255421
2016 Design and synthesis of fluorescent and biotin tagged probes for the study of molecular actions of FAF1 inhibitor. Bioorganic & medicinal chemistry letters 3 26810261
2010 Crystallization and preliminary X-ray crystallographic analysis of human FAF1 UBX domain. Acta crystallographica. Section F, Structural biology and crystallization communications 2 20124726
2025 Evaluation of the role of circular RNA (circ-FAF1) as a diagnostic biomarker for breast cancer in a cohort of Egyptian breast cancer patients. Molecular biology reports 1 39881045
2024 Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function. BMC molecular and cell biology 1 38172660
2011 Crystallization and preliminary X-ray crystallographic analysis of the hexameric human p97/VCP ND1 fragment in complex with the UBX domain of human FAF1. Acta crystallographica. Section F, Structural biology and crystallization communications 1 22102026
2026 The accessory adapters FAF1, FAF2, and UBXN7 accelerate proteasomal degradation by increasing prior p97-mediated substrate unfolding. Science advances 0 41790892
2026 Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement. Cell reports 0 42228561
2025 Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement. bioRxiv : the preprint server for biology 0 41278724
2023 FAF1 Gene Involvement in Pituitary Corticotroph Tumors. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 0 38065537

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