Affinage

UBA5

Ubiquitin-like modifier-activating enzyme 5 · UniProt Q9GZZ9

Length
404 aa
Mass
44.9 kDa
Annotated
2026-06-10
40 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBA5 is the sole E1-activating enzyme that initiates the UFM1 conjugation (ufmylation) cascade, an essential post-translational modification system required for erythroid development, neurodevelopment, ER homeostasis, and genome maintenance (PMID:21304510, PMID:24966333). It activates UFM1 through an unconventional two-step mechanism that forms a binary covalent UBA5~UFM1 thioester on its catalytic Cys250, which uniquely resides within the adenylation domain rather than a separate cysteine-bearing domain as in canonical E1 enzymes (PMID:20368332, PMID:24966333). UBA5 functions as a homodimer that engages UFM1 in trans: UFM1 binds distinct sites across both subunits, stabilizing dimerization and enhancing ATP binding, and the C-terminal region delivers UFM1 to the active site of the adjacent subunit for transthiolation onto the E2 enzyme UFC1 (PMID:27653677, PMID:29295865). A short linear motif in the C-terminal unstructured region (residues 381–404) mediates UFC1 recognition and positions UBA5 next to UFC1's active-site cysteine to drive UFM1 transfer, while an atypical combined LIR/UFIM motif binds both UFM1 and GABARAP, the latter targeting UBA5 to the ER membrane independent of lipidation (PMID:34588452, PMID:25084390, PMID:30990354, PMID:26929408). Downstream of this cascade, UFM1 is conjugated to substrates including Ku70 to promote non-homologous end-joining DNA repair [PMID:bio_10.1101_2025.06.16.659844]. Loss of UBA5 activity impairs ufmylation and produces ER stress and an exacerbated unfolded protein response, defective mitochondrial quality control with inefficient PINK1-Parkin mitophagy, defective erythroid differentiation, and aberrant neurodevelopment with GABAergic interneuron defects (PMID:40333994, PMID:41645284, PMID:21304510). Biallelic hypomorphic and loss-of-function UBA5 variants form a graded allelic series whose biochemical severity correlates with early-onset encephalopathy phenotypes (PMID:38079206, PMID:27545681).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2008 Low

    Established UBA5 as a thioester-forming activating enzyme, the founding observation of its E1 catalytic capacity, though with disputed substrate breadth.

    Evidence In vitro thioester assay, co-immunoprecipitation and immunofluorescence in AD293 cells

    PMID:18442052

    Open questions at the time
    • SUMO2 activation not widely replicated and conflicts with later UFM1-specific consensus
    • subcellular localization assessed by single method
  2. 2010 High

    Resolved why UBA5 is mechanistically atypical by placing its catalytic Cys250 within the adenylation domain rather than a separate cysteine domain, distinguishing it from canonical E1 enzymes.

    Evidence X-ray crystallography of human UBA5–ATP with comparison to canonical E1 enzymes

    PMID:20368332

    Open questions at the time
    • structure did not capture the UFM1-bound or transthiolation state
    • dimeric trans mechanism not yet resolved
  3. 2011 High

    Defined the physiological requirement for UBA5/UFM1 by showing it is indispensable and cell-autonomous for erythroid differentiation, establishing the pathway's developmental importance.

    Evidence Conditional knockout mouse with erythroid-specific transgenic rescue and colony-forming assays

    PMID:21304510

    Open questions at the time
    • molecular ufmylation substrates in erythropoiesis not identified
    • does not address neuronal phenotypes
  4. 2014 High

    Defined the kinetic logic of UFM1 activation, showing a two-step binary thioester mechanism with ATP-dependent transthiolation, and mapped the minimal UFC1-binding C-terminal region.

    Evidence In vitro thioester and ATP-PPi exchange assays, mechanism-based inhibitor probes, truncation analysis with HCT116 cellular assays

    PMID:24966333 PMID:25084390

    Open questions at the time
    • structural basis of UFM1-to-UFC1 transfer not yet visualized
    • regulation of reaction directionality undefined
  5. 2016 High

    Revealed that UBA5 operates as a homodimer engaging UFM1 in trans across the dimer interface, explaining how a single-domain E1 catalyzes both activation and transfer.

    Evidence X-ray crystallography of the UBA5–UFM1 complex with biochemical validation, plus refined UIS boundaries by additional crystallography and mutagenesis

    PMID:27653677 PMID:28360427

    Open questions at the time
    • dynamics of oligomeric transitions in solution not resolved
    • coupling between dimerization and catalysis quantitatively undefined
  6. 2016 High

    Connected UBA5 to membrane targeting by defining a combined LIR/UFIM motif that binds both UFM1 and LC3/GABARAP and is required for full activity.

    Evidence NMR structure, binding assays, and in vitro/cellular transfer assays with mutagenesis

    PMID:26929408

    Open questions at the time
    • functional consequence of ER localization not yet defined
    • selectivity among ATG8 family members not yet resolved
  7. 2016 Medium

    Linked UBA5 to human disease by showing patient mutations impair ufmylation and disrupt ER structure, with model-organism phenotypes establishing a neurological role.

    Evidence Ufmylation assays in patient fibroblasts, C. elegans knockout behavior, zebrafish knockdown, in vitro thioester assays of variants, CNS Ufm1 mouse knockout

    PMID:26872069 PMID:27545674 PMID:27545681

    Open questions at the time
    • genotype–phenotype severity relationship not yet systematized
    • neuronal substrates of ufmylation unidentified
  8. 2017 High

    Established UBA5 as a druggable target by showing covalent modification of its catalytic cysteine blocks UFM1 activation and impairs cancer cell survival and tumor growth.

    Evidence isoTOP-ABPP chemoproteomics, covalent ligand screening, activity and viability assays, xenograft models

    PMID:28186401

    Open questions at the time
    • selectivity over other cysteine-active enzymes not exhaustively characterized
    • downstream ufmylation substrates mediating anti-tumor effect unknown
  9. 2018 Medium

    Defined regulatory coupling whereby UFM1 binding stabilizes the dimer and the long-isoform N-terminal extension tunes ATP affinity and stoichiometry, linking substrate engagement to catalytic competence.

    Evidence Biochemical and biophysical dimerization/binding assays and crystal structures of the long isoform ± UFM1 with ATP

    PMID:29295865 PMID:30412706

    Open questions at the time
    • physiological relevance of isoform-specific ATP regulation in cells untested
    • single-lab biophysical findings
  10. 2019 High

    Explained ATG8-family selectivity, showing the UBA5 LIR prefers GABARAP via a tryptophan inserting into a novel hydrophobic pocket and that GABARAP governs UBA5 ER localization independent of lipidation.

    Evidence NMR/X-ray structures of GABARAP–UBA5 LIR complexes, ITC, swapping mutagenesis, live-cell imaging/fractionation

    PMID:30990354

    Open questions at the time
    • how ER-localized UBA5 selects membrane-proximal substrates unknown
    • functional integration with autophagy machinery undefined
  11. 2021 High

    Resolved the structural basis of UBA5-to-UFC1 transfer, showing an unconventional short linear C-terminal sequence positions UBA5 next to UFC1's active-site cysteine to compensate for a missing loop.

    Evidence X-ray and NMR structures of UBA5 C-terminus–UFC1 complexes with truncation/mutagenesis transfer assays

    PMID:34299007 PMID:34588452

    Open questions at the time
    • transient catalytic intermediate of transthiolation not captured
    • regulation of C-terminal engagement in cells unknown
  12. 2021 Medium

    Characterized the directionality and oligomeric plasticity of the system, showing free UFM1 concentration controls transfer directionality and UBA5 undergoes concentration-dependent oligomeric transitions.

    Evidence Biochemical thioester and cell migration assays with overexpression/knockout lines; SAXS and biophysical oligomeric-state analysis

    PMID:34508858 PMID:35806453

    Open questions at the time
    • physiological conditions controlling UFM1 pool size in cells undefined
    • SAXS oligomeric model from single study
  13. 2023 High

    Systematized genotype–phenotype relationships by building a biochemical allelic series whose loss-of-function severity correlates with in vivo phenotypes, providing a mechanistic framework for UBA5 disease variants.

    Evidence Comprehensive in vitro biochemical assays and a humanized Drosophila UBA5 model across an allelic series

    PMID:38079206

    Open questions at the time
    • does not identify which downstream substrates drive specific clinical features
    • human cellular validation limited
  14. 2025 Medium

    Extended UBA5/UFM1 function to genome maintenance by identifying Ku70 as a UFMylation substrate whose modification promotes NHEJ DNA double-strand break repair.

    Evidence Photo-crosslinkable UFM1 probe, NMR, proximity proteomics, patient fibroblast assays, UFSP2 depletion (preprint)

    PMID:bio_10.1101_2025.06.16.659844

    Open questions at the time
    • preprint, not yet peer-reviewed
    • in vivo relevance of NHEJ defect to disease phenotypes untested
  15. 2025 Medium

    Linked UBA5 to organelle quality control and neurodevelopmental disease mechanism, showing impaired mitophagy and GABAergic interneuron defects with exacerbated UPR in patient-derived models.

    Evidence UBA5 knockout cell mitophagy/ROS/cell-cycle assays and patient-derived cortical organoids with scRNA-seq and electrophysiology

    PMID:40333994 PMID:41645284

    Open questions at the time
    • direct ufmylation substrate linking UBA5 to PINK1-Parkin mitophagy not identified
    • causal substrate for GABAergic defect unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full repertoire of physiological UFM1 substrates and how loss of individual ufmylation events maps onto distinct tissue phenotypes (erythroid, neuronal, mitochondrial, DNA repair) remains unresolved.
  • substrate-to-phenotype mapping incomplete
  • mechanism coupling ER-localized UBA5 to specific substrate selection unknown
  • regulation of pathway directionality in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0140657 ATP-dependent activity 3 GO:0003723 RNA binding 2 GO:0016874 ligase activity 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-73894 DNA Repair 1
Partners
GABARAPGABARAPL2UFC1UFM1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Crystal structure of human UBA5 bound to ATP revealed that the catalytic cysteine (Cys250) is located within the adenylation domain in an alpha-helical motif, unlike other E1 enzymes where the active-site cysteine is in a separate flexible domain. Conformational changes associated with ATP binding provide insight into ubiquityl-enzyme thioester formation. X-ray crystallography with structural comparison to canonical E1 enzymes The Journal of biological chemistry High 20368332
2014 UBA5 activates UFM1 via a two-step mechanism forming a binary covalent UBA5~UFM1 thioester (contrasting with Uba1's three-step ternary mechanism). UBA5 shows random ordered binding with UFM1 and ATP. Binding of ATP to the UBA5~UFM1 thioester is required for efficient transthiolation of UFM1 to UFC1. The pan-E1 inhibitor adenosine 5'-sulfamate (ADS) reacts with the UBA5~UFM1 thioester to form a tight-binding Ufm1-ADS adduct. In vitro thioester formation assay, ATP-PPi exchange assay, mechanism-based inhibitor studies, cellular assays in HCT116 cells The Journal of biological chemistry High 24966333
2016 Crystal structure of the homodimeric UBA5 in complex with UFM1 revealed a trans-binding mechanism: UFM1 interacts with distinct sites on both subunits of the UBA5 dimer, requiring the C-terminal region to bring UFM1 to the active site of the adjacent subunit. Transfer of UFM1 from UBA5 to UFC1 (E2) also occurs via a trans mechanism requiring a UBA5 homodimer. X-ray crystallography of UBA5-UFM1 complex, supporting biochemical experiments Cell reports High 27653677
2016 A combined LIR/UFIM motif at the C-terminus of UBA5 enables binding to both UFM1 and LC3/GABARAP proteins. This motif is required for full biological activity of UBA5 and for effective transfer of UFM1 onto UFC1 and downstream substrate proteins, both in vitro and in cells. NMR structure determination, binding assays, in vitro transfer assays, cellular functional assays with mutagenesis The Journal of biological chemistry High 26929408
2017 Crystal structure of UFM1 fused to 13 amino acids of human UBA5 refined the UFM1-interacting sequence (UIS) boundaries. His336 of UBA5, not previously identified as part of the UIS, occupies a negatively charged pocket on UFM1's surface and is required for UFM1 binding and activation when mutated. A UFM1-UFM1 interaction was found to mimic UIS binding. X-ray crystallography, binding assays, UFM1 activation activity assays with mutagenesis Scientific reports High 28360427
2018 Trans-binding of UFM1 to UBA5 stabilizes the UBA5 homodimer, and UBA5 dimerization is required for ATP binding. UFM1 binding therefore enhances UBA5 affinity for ATP, establishing a regulatory connection between UFM1 engagement and ATP binding by UBA5. Biochemical binding and activity assays, biophysical analysis of dimerization FASEB journal Medium 29295865
2018 The N-terminal extension present in the longer UBA5 isoform directly participates in ATP binding and changes the stoichiometry from 1:2 to 1:1 (ATP:UBA5), significantly increases UBA5 affinity for ATP, and stimulates transfer of UFM1 from UBA5 to UFC1 despite not being directly involved in E2 binding. Crystal structures of long UBA5 isoform ± UFM1 with ATP, biochemical ATP binding and UFM1 transfer assays Journal of molecular biology High 30412706
2019 The non-canonical LIR motif of UBA5 preferentially interacts with GABARAP over LC3 proteins via an additional conserved tryptophan binding into a novel hydrophobic pocket (HP0) on GABARAP surface, with K/R47 in GABARAP as the key specificity residue. GABARAP proteins regulate UBA5 localization and function on the endoplasmic reticulum membrane in a lipidation-independent manner. NMR and X-ray crystal structures of GABARAP/GABARAPL2-UBA5 LIR complexes, swapping mutagenesis, isothermal titration calorimetry, live cell imaging/fractionation Autophagy High 30990354
2021 Crystal structure of UFC1 bound to the C-terminus of UBA5 revealed a short linear sequence mediating the UBA5-UFC1 interaction not observed in other E1-E2 complexes. A region outside the adenylation domain of UBA5 is dispensable for UFC1 binding but critical for UFM1 transfer, moving next to UFC1's active-site Cys to compensate for a missing loop in UFC1. X-ray crystallography of UBA5 C-terminus–UFC1 complex, biochemical UFM1 transfer assays with truncation/mutagenesis Nature communications High 34588452
2021 The last 20 residues of the C-terminal unstructured region of UBA5 are pivotal for binding to UFC1 and accelerate UFM1 transfer to UFC1. NMR structure of UFC1 bound to the last 20 residues of UBA5 revealed the molecular basis of this interaction. NMR spectroscopy of UFC1-UBA5 C-terminal peptide complex, isothermal titration calorimetry, biochemical transfer assays International journal of molecular sciences High 34299007
2021 UFM1 regulates the oligomeric state of UBA5: mixtures of homodimers and heterotrimers are observed in solution, with the UBA5-UFM1 complex undergoing concentration-dependent oligomeric transitions. UBA5 alone transitions from monomeric to dimeric in a concentration-dependent manner with negative cooperativity in complex formation. Small-angle X-ray scattering (SAXS), binding studies, biophysical characterization of oligomeric states Journal of structural biology Medium 34508858
2022 Overexpression of UBA5 (but not UFC1) reverses the trans-thiolation reaction, causing back-transfer of UFM1 from UFC1 to UBA5, thereby reducing charged UFC1 levels and impairing ufmylation. This overexpression phenocopies UBA5 or UFC1 loss in impairing cell migration. Co-expression with UFM1 abolishes the back-transfer, indicating that free UFM1 concentration controls directionality. Biochemical thioester assays, cell migration assays with overexpression and knockout lines International journal of molecular sciences Medium 35806453
2011 Uba5 is the specific E1-activating enzyme for UFM1 and is indispensable for erythroid differentiation in mice. Genetic loss of Uba5 impairs development of megakaryocyte and erythroid progenitors from common myeloid progenitors, causing severe anemia and embryonic death. Transgenic erythroid-specific re-expression of Uba5 rescued anemia, demonstrating cell-autonomous function. Conditional knockout mouse model, transgenic rescue, colony-forming assays Nature communications High 21304510
2016 UBA5 mutations causing early-onset encephalopathy impair ufmylation and result in abnormal endoplasmic reticulum structure in patient fibroblasts. In C. elegans, knockout of uba-5 and UFM1 cascade orthologs alters cholinergic but not glutamatergic neurotransmission. In zebrafish, uba5 silencing decreases motility and induces seizure-like movements. Biochemical ufmylation assays in patient fibroblasts, C. elegans knockout behavioral assays, zebrafish morpholino knockdown American journal of human genetics Medium 27545681
2016 The UBA5 p.Ala371Thr variant is hypomorphic, with attenuated ability to transfer activated UFM1 to UFC1 as shown by in vitro thioester formation assay. CNS-specific knockout of Ufm1 in mice causes neonatal death with microcephaly and apoptosis in specific neurons. In vitro thioester formation assay, conditional CNS Ufm1 knockout mouse model American journal of human genetics High 27545674
2016 UBA5-R246X mutation dramatically decreases protein half-life and abolishes UFM1 activation due to loss of the catalytic Cys250. UBA5-K310E maintains UFM1 interaction with reduced stability. In Drosophila, UBA5 knockdown induces locomotor defects, shortened lifespan, and aberrant neuromuscular junctions; wild-type but not mutant UBA5 restores neural lesions. Protein stability assays, UFM1 activation assays, Drosophila genetic rescue with wild-type vs. mutant UBA5 PloS one Medium 26872069
2008 UBA5 (UBE1DC1) activates not only UFM1 but also SUMO2 in vitro and in vivo by forming a high-energy thioester bond. UBA5 localizes predominantly to the cytoplasm, but redistributes to the nucleus upon co-transfection with SUMO2. In vitro thioester assay, in vivo co-immunoprecipitation, immunofluorescence subcellular localization in AD293 cells Journal of cellular biochemistry Low 18442052
2017 A covalent ligand (DKM 2-93) that modifies the catalytic cysteine of UBA5 inhibits its activity as an E1 enzyme for UFM1, impairs pancreatic cancer cell survival, and reduces in vivo tumor growth, identifying UBA5 catalytic cysteine as a druggable hotspot. isoTOP-ABPP chemoproteomic platform, covalent ligand screening, in vitro activity assays, cell viability assays, xenograft tumor models ACS chemical biology High 28186401
2023 Systematic biochemical assays across UBA5 disease variants established an allelic series with mild, intermediate, and severe loss-of-function grades based on protein stability, ATP binding, UFM1 activation, and UFM1 transthiolation. In vivo Drosophila phenotypes (viability, lifespan, locomotion) strongly correlate with in vitro biochemical severity. Comprehensive in vitro biochemical assays (thermal stability, ATP binding, UFM1 charging, transthiolation), humanized Drosophila UBA5 model eLife High 38079206
2026 UBA5 loss disrupts mitochondrial quality control: UBA5-deficient cells accumulate damaged mitochondria and increased ROS. The PINK1-Parkin damage response is engaged but mitophagy execution is inefficient, resulting in impaired clearance of dysfunctional mitochondria, p53 activation, DNA damage responses, p21-associated G2/M arrest, and early apoptosis. UBA5 knockout cells, mitochondrial morphology assays, ROS measurement, mitophagy flux assays, cell cycle analysis, apoptosis assays Biological research Medium 41645284
2025 UFMylation downstream of UBA5 promotes non-homologous end-joining (NHEJ) DNA double-strand break repair. Ku70 is identified as a UFMylation substrate; UFMylated Ku70 is recognized by XRCC4 to promote chromatin assembly of NHEJ factors. Perturbation via a hypomorphic UBA5 allele in patient-derived fibroblasts impairs these processes. Photo-crosslinkable UFM1 probe, high-resolution NMR, proximity-dependent proteomics, patient-derived fibroblast functional assays, UFSP2 depletion bioRxivpreprint Medium bio_10.1101_2025.06.16.659844
2025 UBA5 function is required for orthoflavivirus (dengue, Zika, West Nile, yellow fever) replication. UFMylation pathway components including UBA5 are selectively recruited to viral replication sites; UFMylation promotes mitochondrial respiration in this context. Pharmacological inhibition of UFMylation reduces viral replication in vitro and in vivo. Proteomic interaction mapping, siRNA knockdown of UFMylation components, pharmacological inhibition, in vitro and in vivo viral replication assays bioRxivpreprint Low bio_10.1101_2025.05.15.653649
2025 Patient-derived cortical organoids with compound heterozygous UBA5 pathogenic variants show defects in GABAergic interneuron development, aberrant neuronal firing, and reduced organoid size. ER homeostasis is perturbed and the unfolded protein response pathway is exacerbated in cells and organoids expressing UBA5 pathogenic variants. Patient-derived cortical organoid culture, single-cell RNA sequencing, electrophysiology, UPR pathway assays Science translational medicine Medium 40333994
2014 UBA5 residues 381–404 constitute the minimal region for UFC1 recognition, while residues 364–404 are necessary for transthiolation of UFM1 to UFC1. The UBA5–UFC1 fusion protein exists as a homodimer in solution. Truncation assays, protein biochemistry, crystallization/preliminary X-ray analysis Acta crystallographica Section F Medium 25084390

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice. Nature communications 150 21304510
2016 Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy. American journal of human genetics 104 27545681
2016 Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy. American journal of human genetics 101 27545674
2017 Chemoproteomic Screening of Covalent Ligands Reveals UBA5 As a Novel Pancreatic Cancer Target. ACS chemical biology 87 28186401
2016 UBA5 Mutations Cause a New Form of Autosomal Recessive Cerebellar Ataxia. PloS one 79 26872069
2010 Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme. The Journal of biological chemistry 69 20368332
2016 Structural and Functional Analysis of a Novel Interaction Motif within UFM1-activating Enzyme 5 (UBA5) Required for Binding to Ubiquitin-like Proteins and Ufmylation. The Journal of biological chemistry 67 26929408
2016 Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex. Cell reports 55 27653677
2019 An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5. Autophagy 46 30990354
2014 Mechanistic study of Uba5 enzyme and the Ufm1 conjugation pathway. The Journal of biological chemistry 43 24966333
2018 Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst. Human mutation 39 29663568
2021 Structural basis for UFM1 transfer from UBA5 to UFC1. Nature communications 38 34588452
2017 Compound heterozygous mutations in UBA5 causing early-onset epileptic encephalopathy in two sisters. BMC medical genetics 36 28965491
2018 An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation. Journal of molecular biology 35 30412706
2008 NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1-UBA5-UFC1 ubiquination pathway. Journal of structural and functional genomics 32 19101823
2021 Inhibition of UBA5 Expression and Induction of Autophagy in Breast Cancer Cells by Usenamine A. Biomolecules 31 34572561
2020 A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy. Journal of medical genetics 31 32179706
2015 A selective inhibitor of the UFM1-activating enzyme, UBA5. Bioorganic & medicinal chemistry letters 30 27520940
2017 Novel insights into the interaction of UBA5 with UFM1 via a UFM1-interacting sequence. Scientific reports 29 28360427
2008 UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins. Journal of cellular biochemistry 29 18442052
2021 A description of novel variants and review of phenotypic spectrum in UBA5-related early epileptic encephalopathy. Cold Spring Harbor molecular case studies 28 33811063
2018 Biallelic loss-of-function UBA5 mutations in a patient with intractable West syndrome and profound failure to thrive. Epileptic disorders : international epilepsy journal with videotape 22 30078785
2018 Trans-binding of UFM1 to UBA5 stimulates UBA5 homodimerization and ATP binding. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 29295865
2014 Characterization, crystallization and preliminary X-ray crystallographic analysis of the human Uba5 C-terminus-Ufc1 complex. Acta crystallographica. Section F, Structural biology communications 17 25084390
2005 Isolation and characterization of ubiquitin-activating enzyme E1-domain containing 1, UBE1DC1. Molecular biology reports 16 16328888
2024 UBA5 inhibition restricts lung adenocarcinoma via blocking macrophage M2 polarization and cisplatin resistance. Experimental cell research 15 38936760
2021 Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy. Neuropediatrics 15 33853163
2021 A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1. International journal of molecular sciences 15 34299007
2023 Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays. eLife 10 38079206
2022 Overexpression of UBA5 in Cells Mimics the Phenotype of Cells Lacking UBA5. International journal of molecular sciences 10 35806453
2023 Genetic model of UBA5 deficiency highlights the involvement of both peripheral and central nervous systems and identifies widespread mitochondrial abnormalities. Brain communications 9 38046095
2025 Patient-derived models of UBA5-associated encephalopathy identify defects in neurodevelopment and highlight potential therapeutic avenues. Science translational medicine 8 40333994
2014 Characterization, crystallization and preliminary X-ray crystallographic analysis of the Uba5 fragment necessary for high-efficiency activation of Ufm1. Acta crystallographica. Section F, Structural biology communications 5 24915089
2021 Structure and dynamics of UBA5-UFM1 complex formation showing new insights in the UBA5 activation mechanism. Journal of structural biology 4 34508858
2024 Patient derived model of UBA5-associated encephalopathy identifies defects in neurodevelopment and highlights potential therapies. bioRxiv : the preprint server for biology 3 38328212
2023 Developmental and epileptic encephalopathy 44 due to compound heterozygous variants in the UBA5 gene: a case report. Acta epileptologica 2 40217280
2026 UBA5 deficiency disrupts mitochondrial autophagy via the PINK1-parkin pathway and impairs myoblast proliferation. Biological research 1 41645284
2025 UBA5-epileptic encephalopathy: new patient, a novel variant, and a review of epileptic phenotypes. Epileptic disorders : international epilepsy journal with videotape 0 40920053
2025 UBA5 missense variants disrupt UFM1 activation: Structural, dynamic, and functional dissection. International journal of biological macromolecules 0 41360240
2023 Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays. medRxiv : the preprint server for health sciences 0 37502976

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