Affinage

BRAP

Bombesin receptor-activated protein C6orf89 · UniProt Q6UWU4

Length
347 aa
Mass
39.9 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 16 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

BRAP (also IMP, BRAP2, RNF52) is a cytoplasmic RING-domain E3 ubiquitin ligase that sets activation thresholds for mitogenic and stress-signaling cascades (PMID:14724641). Its founding function is as a Ras-responsive brake on the Raf-MEK-ERK pathway: BRAP inhibits the scaffold KSR1 by disrupting KSR1 homo-oligomerization and B-Raf/c-Raf hetero-oligomerization, thereby limiting MEK recruitment and c-Raf activation and acting as a threshold modulator rather than altering response timing (PMID:14724641, PMID:18332145). Ras activation drives BRAP auto-polyubiquitination and autodegradation, relieving this inhibition and permitting productive Raf-MEK assembly (PMID:14724641, PMID:19091743); BRAP stability is in turn opposed by the deubiquitylases USP15 and USP4, which counter its autoubiquitination (PMID:23105109). In the developing CNS, BRAP partners with the Nde1-Lis1 complex to tune MAPK thresholds during neural progenitor proliferation and differentiation (PMID:23673330), and BRAP-mediated polyubiquitination of Skp2 restrains G1/S transition, with its loss causing premature S-phase entry and microcephaly (PMID:28768199). Independently of catalysis-driven signaling, BRAP serves as a cytoplasmic retention factor that binds nuclear-localization signals in a phosphorylation-dependent manner to sequester nuclear proteins including p21/CDKN1A, HMG20A, NuMA1, and certain viral cargoes such as SV40 large T antigen (PMID:15340083, PMID:20040518, PMID:23707952). BRAP also restrains NF-κB nuclear translocation through interaction with IKK signalosome components IκBβ and IKKβ and with Nedd8/SCF complexes (PMID:21670849, PMID:23554956), and its loss in mouse brain produces persistent DNA double-strand breaks and elevated histone H2A ubiquitination linked to senescence and neurodegeneration (PMID:35754718). BRAP variants are genetically associated with myocardial infarction (PMID:19198608).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 High

    Established BRAP/IMP as a Ras-responsive E3 ligase that sets the activation threshold of the MAP kinase cascade by inhibiting the KSR scaffold, answering how mitogenic signal amplitude is gated.

    Evidence siRNA depletion, ubiquitination assays, Ras epistasis and MEK activation readouts in mammalian cells

    PMID:14724641

    Open questions at the time
    • Did not resolve the molecular target of KSR inhibition at the oligomerization level
    • Direct ubiquitination substrate within the Raf-MEK module not defined
  2. 2004 Medium

    Showed BRAP2 binds the p21 NLS and retains p21 in the cytoplasm, revealing a ubiquitination-independent role as a nuclear-protein sequestration factor.

    Evidence Reciprocal Co-IP and co-transfection localization assays during monocytic differentiation

    PMID:15340083

    Open questions at the time
    • Single lab
    • Physiological signal triggering p21 release not defined
  3. 2008 Medium

    Defined the mechanism of KSR inhibition, showing IMP disrupts KSR1 homo-oligomerization and Raf hetero-oligomerization to impair MEK recruitment and c-Raf activation.

    Evidence Co-IP, oligomerization and kinase activity assays with IMP expression/depletion

    PMID:18332145

    Open questions at the time
    • Single lab
    • Structural basis of the IMP-KSR interaction not resolved
  4. 2008 Medium

    Demonstrated that Ras controls IMP levels through induction of autoubiquitination/autodegradation, establishing the feedback that licenses signal propagation.

    Evidence Ubiquitination assays, Ras activation experiments, functional rescue

    PMID:19091743

    Open questions at the time
    • Identity of any cofactor enabling auto-degradation not defined
    • Single lab
  5. 2009 High

    Extended cytoplasmic retention to phosphorylation-gated NLS recognition, showing BRAP2 blocks nuclear import of cargo whose NLS-flanking residues are phosphorylated.

    Evidence Nuclear import quantification, site-directed mutagenesis of CDK site T124, pulldown/AlphaScreen binding using SV40 T-ag and HCMV ppUL44

    PMID:20040518

    Open questions at the time
    • Generality of phospho-NLS recognition across endogenous substrates not mapped
    • Kinase responsible for substrate priming not identified
  6. 2009 Medium

    Linked BRAP to cardiovascular disease and NF-κB control, showing BRAP is a galectin-2 binding protein whose knockdown suppresses NF-κB in endothelial cells.

    Evidence Galectin-2 pulldown, siRNA knockdown, NF-κB activation assay; BRAP SNP-MI association

    PMID:19198608

    Open questions at the time
    • Mechanism connecting galectin-2 binding to NF-κB not established
    • SNP association does not establish causal mechanism
  7. 2010 Medium

    Placed BRAP in an oxidative-stress checkpoint, showing brap-2 loss sensitizes C. elegans to paraquat via brc-1-dependent cki-1 induction.

    Evidence C. elegans genetic epistasis with brc-1, paraquat exposure, cki-1 expression analysis

    PMID:20207739

    Open questions at the time
    • Direct molecular link between BRAP-2 and brc-1/cki-1 not defined
    • Mammalian conservation untested here
  8. 2011 Medium

    Mapped BRAP onto the IKK signalosome, showing it interacts with IκBβ and IKKβ and is required for NF-κB nuclear translocation and inflammatory cytokine output.

    Evidence siRNA knockdown, reciprocal Co-IP, NF-κB translocation assay, cytokine ELISA in aortic smooth muscle cells

    PMID:21670849

    Open questions at the time
    • Whether BRAP ubiquitinates IKK components not tested
    • Single lab
  9. 2012 Medium

    Identified USP15/USP4 as deubiquitylases that stabilize BRAP, defining a ubiquitin-cycle regulatory loop affecting MAPK amplitude.

    Evidence Co-IP, domain mapping, ubiquitination and proteasomal degradation rescue, EGF/PDGF signaling assays

    PMID:23105109

    Open questions at the time
    • Single lab
    • In vivo relevance of the USP15-BRAP axis not established
  10. 2013 Medium

    Connected BRAP to neurodevelopmental MAPK threshold control via a Nde1-Lis1-Brap complex acting on KSR.

    Evidence Genetic epistasis (double mutant), Co-IP of Lis1-Brap, in vivo MAPK activation assays in mouse CNS

    PMID:23673330

    Open questions at the time
    • Biochemical role of Lis1 in BRAP catalysis not resolved
    • Single lab
  11. 2013 Medium

    Broadened the cytoplasmic-retention substrate set, showing BRAP2 sequesters HMG20A and NuMA1 and limits SYNE2 nuclear-envelope accumulation in testis.

    Evidence Yeast two-hybrid, Co-IP from testis tissue, quantitative confocal imaging of ectopic BRAP2

    PMID:23707952

    Open questions at the time
    • Functional consequence of retention in spermatogenesis not defined
    • Phospho-dependence of these substrates not tested
  12. 2013 Medium

    Implicated BRAP2 in neddylation-coupled NF-κB timing, showing it binds Nedd8 and the SCF complex to modulate TNF-α-induced nuclear translocation.

    Evidence Co-IP, Nedd8 binding assay, TNF-α stimulation, NF-κB localization, neddylation-site mutant analysis

    PMID:23554956

    Open questions at the time
    • Whether BRAP2 is itself neddylated functionally unresolved
    • Single lab
  13. 2017 High

    Identified Skp2 as a BRAP ubiquitination substrate controlling G1/S timing, explaining how Brap loss causes premature S-phase entry and microcephaly.

    Evidence Conditional mouse knockout, cell cycle analysis, Skp2 ubiquitination assays, p27 levels, differentiation assays

    PMID:28768199

    Open questions at the time
    • Direct ubiquitin linkage type on Skp2 not specified
    • Relationship to BRAP's MAPK role in the same cells not integrated
  14. 2018 Medium

    Established a pro-apoptotic role for BRAP in DNA-damage response, showing BRAP-2 attenuates AKT-1 and PMK-1/SKN-1 survival signaling to permit germline apoptosis.

    Evidence C. elegans deletion mutant, germline apoptosis assays, epistasis with akt-1/pmk-1/skn-1, Co-IP of BRAP-2 with AKT-1 phosphatase

    PMID:29358669

    Open questions at the time
    • Mammalian conservation of the apoptotic axis not demonstrated
    • Mechanism of AKT-1 phosphatase regulation by BRAP-2 not resolved
  15. 2022 Medium

    Linked Brap loss to chromatin and aging pathology, showing brain Brap deletion causes persistent DNA breaks, elevated H2A ubiquitination, senescence and neurodegeneration, with H2Aub also raised in human AD tissue.

    Evidence Conditional mouse brain knockout, DNA damage and H2Aub assays, proteasome and lifespan analysis, human AD brain immunostaining

    PMID:35754718

    Open questions at the time
    • Whether elevated H2Aub is a direct or indirect consequence of BRAP loss not resolved
    • Causal versus correlative role in human AD undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BRAP's distinct activities — KSR/MAPK gating, Skp2 ubiquitination, cytoplasmic NLS retention, NF-κB control and chromatin/H2Aub regulation — are coordinated within a single cell remains unresolved.
  • No unified model integrating ligase activity with non-catalytic retention function
  • Structural basis of substrate selection unknown
  • Whether disease associations reflect MAPK, NF-κB, or chromatin roles unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 3 GO:0140313 molecular sequestering activity 3 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-168256 Immune System 2 R-HSA-1640170 Cell Cycle 1
Partners
HMG20AIKBKBKSR1LIS1NUMA1SKP2USP15USP4
Complex memberships
IKK signalosomeNde1-Lis1-Brap complexSCF/Nedd8 complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 BRAP/IMP (Impedes Mitogenic signal Propagation) is a Ras-responsive E3 ubiquitin ligase that inhibits KSR (a scaffold/adaptor protein), thereby limiting functional assembly of Raf-MEK complexes and suppressing MAP kinase cascade activation. Upon Ras activation, IMP undergoes auto-polyubiquitination, which releases its inhibition of Raf-MEK complex formation. IMP depletion increases stimulus-dependent MEK activation without altering timing or duration of the response, establishing IMP as a threshold modulator. siRNA depletion, ubiquitination assays, epistasis with Ras, Co-IP, MEK activation assays Nature High 14724641
2004 BRAP2 directly interacts with the cell cycle inhibitor p21 in vitro and in vivo through the nuclear localization signal (NLS) of p21 and the C-terminal portion of BRAP2. Co-transfection of BRAP2 causes p21 to localize to the cytoplasm. During monocytic differentiation of U937 and HL-60 cells, BRAP2 expression is upregulated concomitantly with cytoplasmic relocalization of p21, indicating BRAP2 acts as a cytoplasmic retention protein for p21. Co-immunoprecipitation in vitro and in vivo, co-transfection localization assays, immunoblotting during monocyte differentiation Molecular and cellular biology Medium 15340083
2008 IMP inhibits signal propagation through Raf to MEK by disrupting KSR1 homo-oligomerization and B-Raf/c-Raf hetero-oligomerization, thereby impairing both MEK recruitment to activated Raf and c-Raf kinase activation. Human KSR1 promotes assembly of multivalent Raf-MEK complexes required for c-Raf kinase activation, and IMP exploits this property to modulate signal amplitude. Co-immunoprecipitation, KSR1 oligomerization assays, kinase activity assays, IMP expression/depletion The Journal of biological chemistry Medium 18332145
2008 IMP concentrations are directly regulated by Ras through induction of IMP autoubiquitination (autodegradation), permitting productive Raf-MEK complex assembly. The mechanism of inhibition involves KSR inactivation as the key downstream target. Ubiquitination assays, Ras activation experiments, functional rescue assays The Journal of biological chemistry Medium 19091743
2009 BRAP was identified as a galectin-2-binding protein. SNPs in BRAP are associated with myocardial infarction. BRAP knockdown by siRNA in cultured coronary endothelial cells suppressed activation of NF-κB. Binding assay (galectin-2 pulldown), siRNA knockdown, NF-κB activation assay Nature genetics Medium 19198608
2011 BRAP knockdown in human aortic smooth muscle cells attenuated cell proliferation and reduced secretion of MCP-1 and IL-8 in response to LPS, and prohibited NF-κB nuclear translocation without affecting NF-κB protein levels. Co-immunoprecipitation confirmed interaction between BRAP and IκBβ and IKKβ, two major components of the IKK signalosome. siRNA knockdown, co-immunoprecipitation, NF-κB nuclear translocation assay, cytokine ELISA Molecular medicine (Cambridge, Mass.) Medium 21670849
2012 BRAP/IMP E3 ubiquitin ligase interacts with deubiquitylases USP15 and USP4 through the N-terminal DUSP-UBL domain of USP15 and the coiled-coil region of BRAP. USP15 and USP4 oppose BRAP autoubiquitination, while BRAP promotes USP15 ubiquitylation. USP15 depletion destabilizes BRAP via proteasomal degradation; catalytically active USP15 rescues BRAP levels. USP15 depletion decreases MAPK signaling amplitude in response to EGF and PDGF, in part through decreased CRAF levels. Co-immunoprecipitation, domain mapping, ubiquitination assays, siRNA depletion, proteasomal degradation assay, EGF/PDGF signaling assays The Journal of biological chemistry Medium 23105109
2013 Brap directly interacts with Lis1, and a Nde1-Lis1-Brap complex regulates MAPK signaling thresholds in the developing mammalian CNS. Nde1-Lis1 deficiency causes spatially dependent alterations of the MAPK scaffold KSR and hyperactivation of MAPK. Epistasis analyses supported synergistic Brap and Lis1 functions in controlling neural progenitor proliferation and differentiation. Genetic epistasis analysis (double mutant), co-immunoprecipitation (Lis1-Brap interaction), MAPK activation assays in vivo, mouse CNS developmental phenotype analysis Developmental cell Medium 23673330
2013 Brap2 is a novel Nedd8-binding protein that interacts with the SCF ubiquitin ligase complex and is involved in NF-κB nuclear translocation following TNF-α stimulation. A putative neddylation site in Brap2 is associated with NF-κB activity. Brap2 modulates temporal control of NF-κB nuclear translocation mediated by inflammatory response. Co-immunoprecipitation, Nedd8 binding assay, TNF-α stimulation assay, NF-κB localization assay, neddylation site mutant analysis PloS one Medium 23554956
2009 BRAP2 inhibits nuclear import of specific viral proteins (SV40 large T antigen and HCMV ppUL44) in a manner dependent on phosphorylation sites flanking their nuclear localization signals. Substitution of CDK phosphorylation site T124 of T-ag with Ala prevented BRAP2 inhibition, while Asp (phosphomimetic) enhanced it. Direct high-affinity binding of BRAP2(442-592) to T-ag(111-135) was strictly dependent on negative charge at T124 and the NLS, demonstrated by pulldown/AlphaScreen assays. No effect of BRAP2 was observed on HSV-1 pUL30 (which lacks a phosphorylation site near its NLS) or HIV-1 Tat. Ectopic expression in COS-7 and HL-60 cells, nuclear import quantification, site-directed mutagenesis, pulldown/AlphaScreen binding assay FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 20040518
2013 BRAP2 acts as a cytoplasmic retention factor for testicular nuclear proteins HMG20A and NuMA1, and prevents nuclear envelope accumulation of SYNE2. Co-immunoprecipitation confirmed association of BRAP2 with HMG20A, NuMA1, and SYNE2 in testis. Ectopic expression of BRAP2 inhibited nuclear localization of HMG20A and NuMA1, and prevented nuclear envelope accumulation of SYNE2 in cultured cells. Yeast two-hybrid screen, co-immunoprecipitation from testis tissue, quantitative confocal microscopy of ectopic BRAP2 expression Biochimica et biophysica acta Medium 23707952
2017 Loss of Brap in mouse neural progenitor cells results in premature G1/S phase transition due to elevated Skp2 (SCF ubiquitin ligase component), which increases p27Kip1 destruction. Brap-mediated polyubiquitination of Skp2 was identified as a key regulatory step. Loss of Brap led to elevated Skp2, shortened G1 phase, premature S phase entry, hindered S phase progression, increased G2 arrest, impeded neuronal differentiation, and microcephaly. Conditional Brap mouse knockout, cell cycle analysis, ubiquitination assays for Skp2, p27 protein levels, neuronal differentiation assays Cell reports High 28768199
2018 In C. elegans, BRAP-2 promotes DNA damage-induced germline apoptosis by attenuating pro-survival signals of AKT-1 and PMK-1/SKN-1. Loss of brap-2 reduces germline apoptosis after DNA damage and increases skn-1 mRNA. The interaction between BRAP-2 and the AKT-1 phosphatase (C. elegans homolog of PHLPP1/2) is conserved. SKN-1 RNAi or loss of pmk-1 in brap-2 mutants restored apoptosis to wild-type levels. C. elegans brap-2 deletion mutant, germline apoptosis assays, genetic epistasis with brc-1/akt-1/pmk-1/skn-1, mRNA quantification, co-immunoprecipitation of BRAP-2 with AKT-1 phosphatase Cell death and differentiation Medium 29358669
2010 In C. elegans, developmental arrest of brap-2 deletion mutants under oxidative stress is dependent on brc-1 (BRCA1 ortholog) and requires enhanced expression of the cell cycle inhibitor cki-1 through brc-1. Loss of brap-2 sensitizes animals to paraquat-induced larval arrest at the L1 stage. C. elegans genetic analysis, paraquat exposure, double mutant epistasis with brc-1, cki-1 expression analysis The Journal of biological chemistry Medium 20207739
2015 BRAP overexpression in human bronchial epithelial cells inhibited both basal and inducible NF-κB transcriptional activity, while BRAP knockdown had the opposite effect. BRAP regulates NF-κB activity by enhancing histone deacetylase (HDAC) activity, mediated through its putative C-terminal domain. Gene transfer overexpression, siRNA knockdown, NF-κB reporter assay, HDAC activity assay, domain truncation analysis Journal of cellular biochemistry Low 26460487
2022 Deletion of Brap in mouse brain causes persistent DNA double-strand breaks and elevation of histone H2A mono- and poly-ubiquitination (H2Aub), leading to cellular senescence, proteasome-mediated histone H2A proteolysis, neuroinflammation, impaired proteostasis, accelerated neurodegeneration, and shortened lifespan. H2Aub elevation also occurs in human Alzheimer's disease brain tissue, suggesting H2Aub chromatin aberrations act as a nexus linking multiple aging hallmarks. Conditional Brap mouse brain knockout, DNA damage assays, H2A ubiquitination assays, proteasome activity assays, lifespan analysis, human AD brain tissue immunostaining iScience Medium 35754718

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Characterization of human type I and type II IMP dehydrogenases. The Journal of biological chemistry 317 7903306
2002 Imp/OstA is required for cell envelope biogenesis in Escherichia coli. Molecular microbiology 218 12207697
2004 Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP. Nature 161 14724641
1980 AMP deamination and IMP reamination in working skeletal muscle. The American journal of physiology 147 7395984
2019 IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma. Nature cell biology 142 31371825
2012 The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature 135 22660319
2001 Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem. Antimicrobial agents and chemotherapy 124 11302793
2016 Enhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival. Cell reports 120 27068461
1999 Consequences of IMP dehydrogenase inhibition, and its relationship to cancer and apoptosis. Current medicinal chemistry 112 10390601
2001 A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking. Scandinavian journal of clinical and laboratory investigation. Supplementum 111 11713986
2011 IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2. Cancer research 104 21252116
2019 Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story. Cancers 101 31514446
2011 IMP-type metallo-β-lactamases in Gram-negative bacilli: distribution, phylogeny, and association with integrons. Critical reviews in microbiology 85 21707466
2009 SNPs in BRAP associated with risk of myocardial infarction in Asian populations. Nature genetics 81 19198608
2011 A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains. PLoS genetics 80 22022282
1999 Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents. Current medicinal chemistry 77 10390603
1999 IMP dehydrogenase: mechanism of action and inhibition. Current medicinal chemistry 74 10390600
2018 IMP/GTP balance modulates cytoophidium assembly and IMPDH activity. Cell division 73 29946345
2015 Dominance of IMP-4-producing enterobacter cloacae among carbapenemase-producing Enterobacteriaceae in Australia. Antimicrobial agents and chemotherapy 69 25918153
2020 Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability. eLife 68 31934860
1990 Cell differentiation and altered IMP dehydrogenase expression induced in human T-lymphoblastoid leukemia cells by mycophenolic acid and tiazofurin. Experimental cell research 65 1967583
2006 IMP dehydrogenase inhibitor mycophenolate mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells. Molecular cancer therapeutics 64 16505121
2011 The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors. Current medicinal chemistry 63 21517780
2017 Imp and Syp RNA-binding proteins govern decommissioning of Drosophila neural stem cells. Development (Cambridge, England) 62 28851709
2016 Isolation and plasmid characterization of carbapenemase (IMP-4) producing Salmonella enterica Typhimurium from cats. Scientific reports 62 27767038
2006 A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP. The Journal of cell biology 59 16476777
2019 The structural basis for RNA selectivity by the IMP family of RNA-binding proteins. Nature communications 58 31570709
2012 bla(IMP) and bla(VIM) mediated carbapenem resistance in Pseudomonas and Acinetobacter species in India. Journal of infection in developing countries 58 23277500
2001 Regulation of an IMP dehydrogenase gene and its overexpression in drug-sensitive transcription elongation mutants of yeast. The Journal of biological chemistry 56 11441018
1990 Expression of IMP dehydrogenase in differentiating HL-60 cells. Blood 55 1967537
2014 Imp promotes axonal remodeling by regulating profilin mRNA during brain development. Current biology : CB 50 24656828
2004 The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins. Proceedings of the National Academy of Sciences of the United States of America 50 15469912
2010 Role of the RNA-binding protein IMP-2 in muscle cell motility. Molecular and cellular biology 49 20956565
2006 IMP dehydrogenase: structural schizophrenia and an unusual base. Current opinion in chemical biology 47 16919497
2018 Immune Response-Dependent Assembly of IMP Dehydrogenase Filaments. Frontiers in immunology 45 30555474
2004 Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation. Molecular and cellular biology 43 15340083
2012 Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15. The Journal of biological chemistry 42 23105109
2000 IMP and AMP deaminase in reperfusion injury down-regulates neutrophil recruitment. Proceedings of the National Academy of Sciences of the United States of America 42 10760293
2006 Imp associates with squid and Hrp48 and contributes to localized expression of gurken in the oocyte. Molecular and cellular biology 41 17030623
2021 Evaluation of the Immunochromatographic NG-Test Carba 5, RESIST-5 O.O.K.N.V., and IMP K-SeT for Rapid Detection of KPC-, NDM-, IMP-, VIM-type, and OXA-48-like Carbapenemase Among Enterobacterales. Frontiers in microbiology 40 33519761
2011 BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis. Molecular medicine (Cambridge, Mass.) 40 21670849
2009 IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue. Human pathology 40 19698973
2009 The BRCA-1 binding protein BRAP2 is a novel, negative regulator of nuclear import of viral proteins, dependent on phosphorylation flanking the nuclear localization signal. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 20040518
2016 'Rod and ring' formation from IMP dehydrogenase is regulated through the one-carbon metabolic pathway. Journal of cell science 36 27343244
1995 GTP depletion induced by IMP dehydrogenase inhibitors blocks RNA-primed DNA synthesis. Molecular pharmacology 36 7746281
2022 Comprehensive Analysis of Imipenemase (IMP)-Type Metallo-β-Lactamase: A Global Distribution Threatening Asia. Antibiotics (Basel, Switzerland) 35 35203838
2021 Emergence of Tigecycline Nonsusceptible and IMP-4 Carbapenemase-Producing K2-ST65 Hypervirulent Klebsiella pneumoniae in China. Microbiology spectrum 35 34704778
2016 Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP-dependent biogenesis pathway. EMBO reports 35 27226123
2020 Carbapenem-Resistant Enterobacter hormaechei ST1103 with IMP-26 Carbapenemase and ESBL Gene bla SHV-178. Infection and drug resistance 34 32110070
2012 Molecular characterization of IMP-type metallo-β-lactamases among multidrug-resistant Achromobacter xylosoxidans. The Journal of antimicrobial chemotherapy 33 22577105
2002 IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase. The Journal of biological chemistry 31 12004071
1999 IMP dehydrogenase : structural aspects of inhibitor binding. Current medicinal chemistry 31 10390598
2013 Spatially dependent dynamic MAPK modulation by the Nde1-Lis1-Brap complex patterns mammalian CNS. Developmental cell 30 23673330
2023 In silico designing and immunoinformatics analysis of a novel peptide vaccine against metallo-beta-lactamase (VIM and IMP) variants. PloS one 27 37471423
2014 The role of IMP dehydrogenase 2 in Inauhzin-induced ribosomal stress. eLife 27 25347121
2011 Oncofetal protein, IMP-3, a potential marker for prediction of postoperative peritoneal dissemination in gastric adenocarcinoma. Journal of surgical oncology 27 22012575
1992 Cell cycle dependent regulation of IMP dehydrogenase activity and effect of tiazofurin. Life sciences 27 1357518
2015 Drosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation. Genome biology 26 26054396
1997 IMP-L3, A 20-hydroxyecdysone-responsive gene encodes Drosophila lactate dehydrogenase: structural characterization and developmental studies. Developmental genetics 26 9094207
2022 The gateway to guanine nucleotides: Allosteric regulation of IMP dehydrogenases. Protein science : a publication of the Protein Society 25 36040265
2011 Additive effect of ANRIL and BRAP polymorphisms on ankle-brachial index in a Taiwanese population. Circulation journal : official journal of the Japanese Circulation Society 25 22122968
2019 The Bateman domain of IMP dehydrogenase is a binding target for dinucleoside polyphosphates. The Journal of biological chemistry 24 31416831
2018 Specific expression pattern of IMP metabolism related-genes in chicken muscle between cage and free range conditions. PloS one 24 30133460
1993 Chromosomal localization and structure of the human type II IMP dehydrogenase gene (IMPDH2). Genomics 24 8098009
2024 The conserved RNA-binding protein Imp is required for the specification and function of olfactory navigation circuitry in Drosophila. Current biology : CB 23 38181792
2017 Loss of Brap Results in Premature G1/S Phase Transition and Impeded Neural Progenitor Differentiation. Cell reports 23 28768199
1993 IMP dehydrogenase inhibitors as immunomodulators. Annals of the New York Academy of Sciences 23 8103312
1983 IMP dehydrogenase. II. Purification and properties of the enzyme from Yoshida sarcoma ascites tumor cells. Journal of biochemistry 23 6140264
2018 blaIMP-27 on transferable plasmids in Proteus mirabilis and Providencia rettgeri. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 22 29496594
2009 IMP-3 expression in melanocytic lesions. Journal of cutaneous pathology 22 19788446
1990 The Drosophila IMP-E2 gene encodes an apically secreted protein expressed during imaginal disc morphogenesis. Developmental biology 22 2115480
2017 Sequencing of blaIMP-Carrying IncN2 Plasmids, and Comparative Genomics of IncN2 Plasmids Harboring Class 1 Integrons. Frontiers in cellular and infection microbiology 20 28424761
2017 Inhibition of Calcineurin or IMP Dehydrogenase Exerts Moderate to Potent Antiviral Activity against Norovirus Replication. Antimicrobial agents and chemotherapy 20 28807916
2019 IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae. mSphere 19 31666316
2017 Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese by exome-wide association studies. Oncotarget 19 28562329
2013 IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study. European journal of histochemistry : EJH 19 23549465
2008 IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. The Journal of biological chemistry 19 18332145
2002 Metabolism of the novel IMP dehydrogenase inhibitor benzamide riboside. Current medicinal chemistry 19 11966442
2013 Brap2 regulates temporal control of NF-κB localization mediated by inflammatory response. PloS one 18 23554956
2015 IMP-GMP specific cytosolic 5'-nucleotidase regulates nucleotide pool and prodrug metabolism. Biochimica et biophysica acta 16 25857773
2008 Signaling threshold regulation by the Ras effector IMP. The Journal of biological chemistry 16 19091743
2023 Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents. Microbiology spectrum 15 37409948
2021 Emergence of IMP-8-Producing Comamonas thiooxydans Causing Urinary Tract Infection in China. Frontiers in microbiology 15 33790873
2021 First Report of bla IMP-4 and bla SRT-2 Coproducing Serratia marcescens Clinical Isolate in China. Frontiers in microbiology 15 34659175
2013 The BRCA1-binding protein BRAP2 can act as a cytoplasmic retention factor for nuclear and nuclear envelope-localizing testicular proteins. Biochimica et biophysica acta 15 23707952
2022 Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-β-lactamases. Journal of biochemistry 14 36174533
2020 Structure and Molecular Recognition Mechanism of IMP-13 Metallo-β-Lactamase. Antimicrobial agents and chemotherapy 14 32205343
1994 Gene amplification and dual point mutations of mouse IMP dehydrogenase associated with cellular resistance to mycophenolic acid. Biochimica et biophysica acta 14 7906545
1994 Purification and some properties of an IMP-specific 5'-nucleotidase from yeast. The Biochemical journal 14 8141771
1992 Sequence and expression of IMP-L1, an ecdysone-inducible gene expressed during Drosophila imaginal disc morphogenesis. Developmental genetics 14 1292892
2024 IMP: bridging the gap for medicinal plant genomics. Nucleic acids research 13 37870445
2023 Characterization of a Conjugative Hybrid Plasmid Coharboring blaKPC-2 and blaIMP-4 in a Klebsiella quasipneumoniae Clinical Isolate. Microbiology spectrum 13 36625668
2022 Histone H2A ubiquitination resulting from Brap loss of function connects multiple aging hallmarks and accelerates neurodegeneration. iScience 13 35754718
2018 BRAP-2 promotes DNA damage induced germline apoptosis in C. elegans through the regulation of SKN-1 and AKT-1. Cell death and differentiation 13 29358669
2015 EGF enhances low-invasive cancer cell invasion by promoting IMP-3 expression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 26386725
2015 Bombesin Receptor-Activated Protein (BRAP) Modulates NF-κB Activation in Bronchial Epithelial Cells by Enhancing HDAC Activity. Journal of cellular biochemistry 13 26460487
2009 Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori. BMC microbiology 13 19594901
2012 The single nucleotide polymorphisms in BRAP decrease the risk of metabolic syndrome in a Chinese young adult population. Diabetes & vascular disease research 12 22965072
2010 Developmental arrest of Caenorhabditis elegans BRAP-2 mutant exposed to oxidative stress is dependent on BRC-1. The Journal of biological chemistry 12 20207739
2008 Embryonic expression of Drosophila IMP in the developing CNS and PNS. Gene expression patterns : GEP 12 19111951

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