Affinage

RNF7

RING-box protein 2 · UniProt Q9UBF6

Round 2 corrected
Length
113 aa
Mass
12.7 kDa
Annotated
2026-04-28
130 papers in source corpus 45 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF7 (SAG/RBX2/ROC2) is the RING-box component of CUL5-based Cullin-RING E3 ubiquitin ligase (CRL5) complexes and functions as a critical regulator of protein turnover governing apoptosis, NF-κB and mTOR signaling, cell cycle progression, vascular development, neuronal migration, and immune cell activation. RNF7 selectively pairs with the E2 neddylation enzyme UBE2F to activate CUL5 by neddylation and with UBCH10/UBE2S to catalyze K11-linked polyubiquitination, distinguishing it biochemically from its paralog RBX1 (PMID:19250909, PMID:27910872). Through association with different substrate adaptors (β-TrCP, FBXW7, SOCS-box proteins), RNF7-containing CRL complexes target a broad substrate repertoire — including IκBα, NOXA, p27, NF1, DEPTOR, PHLPP1, c-Jun, pro-caspase-3, β-TrCP1, Erbin, SOCS1, Bax, SARM, and DAB1 — for ubiquitin-dependent degradation, thereby controlling context-dependent oncogenic and tumor-suppressive outputs (PMID:17846172, PMID:24430184, PMID:24210661, PMID:27955654). Sag/Rbx2 knockout in mice is embryonic lethal with severe vascular and neural tube defects caused by accumulation of NF1 and impaired RAS-MAPK signaling, and tissue-specific deletions reveal essential roles in endothelial angiogenesis, cortical/cerebellar neuron positioning, retinal lamination, and T-cell activation (PMID:22118770, PMID:24213570, PMID:24210661, PMID:27543965).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    Identification of SAG/RNF7 as a zinc/copper-binding RING finger protein with intrinsic antioxidant activity established the gene's initial functional identity as an anti-apoptotic, redox-protective factor independent of its later-discovered E3 ligase role.

    Evidence Bacterially purified protein biochemistry (metal binding, lipid peroxidation), stable transfection, RING domain mutagenesis

    PMID:10082581 PMID:10443936 PMID:10506102

    Open questions at the time
    • Whether antioxidant activity operates independently of ubiquitin ligase activity in vivo remains unclear
    • No structural model of the disulfide-based ROS-scavenging mechanism
  2. 1999 High

    Demonstrating that SAG/ROC2 binds CUL1 and reconstitutes SCF-type E3 ubiquitin ligase activity repositioned RNF7 from a standalone antioxidant to a core component of the Cullin-RING ligase machinery, with IκBα as an early validated substrate.

    Evidence Yeast two-hybrid, co-immunoprecipitation, in vitro reconstituted ubiquitination with E1/E2/CUL1 and SCF components

    PMID:10230406 PMID:10230407 PMID:10851089

    Open questions at the time
    • Whether SAG preferentially functions with CUL1 or CUL5 was not resolved
    • Substrate specificity determinants were unknown
  3. 2000 High

    Yeast knockout and complementation showed that the SAG homolog is essential for viability and that RING domain-dependent E3 ligase activity — not antioxidant activity alone — is required for cell survival.

    Evidence Yeast gene disruption, tetrad analysis, complementation with wild-type vs. RING mutant human SAG

    PMID:10851089

    Open questions at the time
    • Essential substrates in yeast were not identified
    • Not tested whether the yeast requirement reflects CUL5 vs. CUL1 function
  4. 2004 High

    Domain-swap and RNAi experiments resolved the longstanding question of CRL specificity: SOCS-box proteins assemble with CUL5-RBX2/RNF7 while VHL-box proteins assemble with CUL2-RBX1, establishing RNF7 as the dedicated RING for CRL5 complexes.

    Evidence Endogenous co-immunoprecipitation, Cul-box domain-swap mutagenesis, siRNA knockdown with HIF-2α degradation readout

    PMID:15601820

    Open questions at the time
    • Whether RNF7 can functionally substitute for RBX1 in any CUL1 context remained debated
    • Structural basis of CUL5-RBX2 selectivity was not determined
  5. 2006 High

    Identification of pro-caspase-3 as a substrate of SAG-SCF(β-TrCP) demonstrated that RNF7-containing CRLs directly regulate apoptosis execution machinery, expanding the substrate repertoire beyond cell cycle regulators.

    Evidence Co-immunoprecipitation, in vitro ubiquitination, siRNA knockdown of SAG/ROC1/β-TrCP, dominant-negative β-TrCP

    PMID:17217622

    Open questions at the time
    • Phosphodegron on pro-caspase-3 not fully mapped
    • Relative contributions of SAG vs. ROC1 to caspase-3 regulation not quantified
  6. 2007 High

    Discovery of transcriptional feedback loops — HIF-1 induces SAG under hypoxia and AP-1 induces SAG constitutively, while SAG reciprocally degrades HIF-1α (via CUL5-VHL) and c-Jun (via Fbw7-SCF) — revealed autoregulatory circuits that integrate SAG expression with its substrate turnover.

    Evidence ChIP, EMSA, luciferase reporters, siRNA knockdown, c-Jun and HIF-1α ubiquitination/half-life assays

    PMID:17440073 PMID:17828303

    Open questions at the time
    • Quantitative dynamics of these feedback loops are uncharacterized
    • Whether the HIF-1/SAG loop operates through CUL5 exclusively or also CUL2 was not resolved
  7. 2007 High

    Transgenic mouse skin carcinogenesis studies revealed that SAG exhibits stage-dependent substrate switching: targeting c-Jun/AP-1 at early stages (tumor-suppressive) and IκBα at late stages (tumor-promoting via NF-κB activation), explaining paradoxical roles in cancer.

    Evidence K14-SAG transgenic mice, AP-1 reporter mice, DMBA/TPA two-stage carcinogenesis model

    PMID:17846172

    Open questions at the time
    • Molecular signal that triggers the adaptor/substrate switch is unknown
    • Whether stage-dependent switching occurs in non-skin tissues is untested
  8. 2009 High

    Biochemical reconstitution and structural analysis established that UBE2F is the dedicated NEDD8-conjugating E2 for RBX2/RNF7, selectively neddylating CUL5, while UBE2M neddylates CUL1-4 via RBX1 — defining a fundamental axis of CRL activation specificity.

    Evidence In vitro neddylation assay with purified components, structural analysis of E1-E2 interfaces, mutagenesis

    PMID:19250909

    Open questions at the time
    • Crystal structure of the UBE2F-RBX2 catalytic complex not available
    • Regulation of UBE2F expression/stability not addressed
  9. 2011 High

    Sag knockout in mice proved embryonic lethality (E11.5–12.5) and identified NF1 as a physiological SAG-CUL1-FBXW7 substrate; genetic epistasis (Sag/Nf1 double KO) partially rescued vascular defects, demonstrating that RAS pathway hyperactivation via NF1 accumulation causes the lethal phenotype.

    Evidence Conditional Sag knockout mice, Sag/Nf1 double knockout epistasis, ES cell differentiation, teratoma angiogenesis

    PMID:22118770

    Open questions at the time
    • Neural defects in Sag-null embryos not fully rescued by Nf1 deletion, suggesting additional substrates
    • Contribution of CUL5-based complexes to embryonic phenotype not dissected
  10. 2011 High

    DEPTOR was identified as a substrate of SCF(β-TrCP)/SAG through phosphodegron-mediated recognition, linking SAG directly to mTOR pathway activation via a positive feedback loop (growth factor → RSK1/S6K1 → DEPTOR phosphorylation → SCF-mediated degradation → mTOR activation).

    Evidence Protein half-life assays, co-immunoprecipitation, phosphodegron mutagenesis, kinase inhibitors — independently replicated by three labs

    PMID:22017875 PMID:22017876 PMID:22017877

    Open questions at the time
    • Relative roles of SAG vs. RBX1 in DEPTOR degradation not quantified
    • Whether other phosphodegrons in DEPTOR contribute is unclear
  11. 2011 High

    Reconstitution of a six-protein HIV-1 Vif/CUL5/ELOB/ELOC/CBF-β/RBX2 complex demonstrated that viral hijacking of the CRL5 machinery requires RNF7 for APOBEC3G polyubiquitination, establishing a direct role for RNF7 in viral immune evasion.

    Evidence Affinity purification-mass spectrometry, reconstituted six-protein in vitro ubiquitination assay, RNA knockdown, genetic complementation

    PMID:22190037

    Open questions at the time
    • Structural basis of Vif preferring RBX2 over RBX1 not determined at atomic resolution
    • Whether other viral proteins exploit CRL5-RBX2 similarly is unexplored
  12. 2013 High

    Conditional Rbx2 knockout in the brain revealed that CRL5-RBX2 controls neuronal migration by promoting DAB1 degradation via the SOCS7 adaptor, establishing that proper cortical and cerebellar lamination requires RBX2-dependent Reelin signal termination.

    Evidence Rbx2 conditional knockout mice, in utero electroporation, SOCS7 gain/loss-of-function, DAB1 protein accumulation, epistasis with Reelin pathway

    PMID:24210661

    Open questions at the time
    • The CRL5 adaptor controlling cerebellar (non-SOCS7) neuronal positioning is unknown
    • Whether RBX2 loss affects adult neuronal plasticity is untested
  13. 2013 High

    Endothelial-specific Sag deletion (E15.5 lethal) and p27 knockdown rescue showed that SAG is required for endothelial migration, proliferation, and tube formation through p27 degradation, explaining the vascular defects in global Sag knockouts.

    Evidence Tie2-Cre conditional KO, primary endothelial cell culture assays, p27 knockdown rescue, in vivo Matrigel plug and B16F10 tumor angiogenesis

    PMID:24213570

    Open questions at the time
    • Which F-box protein mediates p27 ubiquitination in the SAG complex in endothelial cells is not defined
    • Contribution of CUL5 vs. CUL1 in vascular SAG function not distinguished
  14. 2014 High

    Biophysical reconstitution of the complete SOCS2-EloBC-CUL5-RBX2 complex demonstrated it exists as a monomer and established interaction affinities within the complex, providing the first complete structural framework for a CRL5 module.

    Evidence Recombinant expression, SEC-MALS, native MS, ITC, ion mobility MS

    PMID:25247507

    Open questions at the time
    • High-resolution crystal or cryo-EM structure of the full complex not available
    • How neddylation changes conformational dynamics not resolved at structural level
  15. 2016 High

    Distinguishing SAG from RBX1 at the E2-binding level showed that SAG specifically recruits UBCH10/UBE2S to build K11-linked ubiquitin chains (targeting β-TrCP1), while RBX1 uses CDC34/UBCH5C for K48 chains — establishing a fundamental biochemical distinction between the two RING-box paralogs.

    Evidence E2 co-immunoprecipitation, protein half-life assays, E2-specific siRNA with substrate accumulation readouts

    PMID:27910872

    Open questions at the time
    • Structural basis for SAG preferring UBCH10/UBE2S is unknown
    • Whether all SAG substrates are modified with K11 chains or some use K48 is not resolved
  16. 2016 Medium

    T-cell-specific Sag knockout revealed that SAG is dispensable for T-cell development but required for T-cell activation and proliferation, with SOCS accumulation as the likely mechanism, extending SAG function to adaptive immunity.

    Evidence T-cell-specific conditional Sag KO mice, in vitro stimulation, allogeneic BMT model, MLN4924 treatment

    PMID:27543965

    Open questions at the time
    • Specific SOCS family member(s) responsible not identified
    • Whether CRL5 or CRL1 mediates SOCS degradation in T cells is unclear
    • Single lab study without independent replication
  17. 2016 High

    Lung-specific Sag deletion suppressed KrasG12D-driven tumorigenesis with accumulation of p21, p27, NOXA, BIM, and DEPTOR; epistatic rescue by p21 or DEPTOR knockdown confirmed their causal roles, solidifying SAG as a multi-substrate oncogenic E3 ligase in Kras-driven cancer.

    Evidence Lung-specific Sag conditional KO in KrasG12D mice, double-knockdown rescue experiments

    PMID:24430184

    Open questions at the time
    • Relative contribution of each substrate to tumor suppression not quantified individually
    • Whether therapeutic SAG inhibition is tolerated in normal lung tissue is unknown
  18. 2018 Medium

    RBX2 was shown to control retinal lamination through DAB1/SOCS7-dependent and SOCS7-independent pathways, extending the neuronal migration paradigm from cortex/cerebellum to the retina and revealing that cone photoreceptor positioning requires an as-yet-unidentified CRL5 adaptor.

    Evidence In vivo shRNA knockdown of RBX2 and SOCS7, retinal electrophysiology (ERG), immunohistochemistry

    PMID:29361558

    Open questions at the time
    • Identity of the CRL5 adaptor for cone photoreceptor positioning unknown
    • shRNA-based approach; conditional KO confirmation pending

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for RBX2-specific E2 (UBE2F, UBCH10) recruitment, the signals that determine substrate-adaptor switching in different tissue/disease contexts, and whether the intrinsic antioxidant activity of RNF7 operates independently of its E3 ligase function in physiological settings.
  • No high-resolution structure of RBX2 in complex with UBE2F or UBCH10
  • Mechanism controlling stage-dependent adaptor switching remains unknown
  • In vivo separation of antioxidant vs. E3 ligase functions not achieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 8 GO:0140096 catalytic activity, acting on a protein 7 GO:0016209 antioxidant activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3
Partners
BTRCCUL1CUL5FBXW7NEDD4UBCH10UBE2FUBE2S
Complex memberships
CRL5 (CUL5-RBX2-ElonginB/C-SOCS-box)SCF (CUL1-RBX2-SKP1-F-box)Vif-CUL5-ElonginBC-CBFβ-RBX2

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SAG/RBX2 (RNF7) was cloned as a novel zinc RING finger protein that binds zinc and copper metal ions, prevents copper-induced lipid peroxidation, forms inter- and intramolecular disulfide bonds in response to oxidative stress, and protects cells from apoptosis induced by redox agents; the C-terminal RING finger domain is required for anti-apoptosis activity. Bacterially expressed/purified protein biochemical assays (metal binding, lipid peroxidation), stable transfection, RING domain mutagenesis, oligomerization assays with DTT/H2O2 Molecular and cellular biology / Free radical biology & medicine / Carcinogenesis High 10082581 10443936 10506102
1999 SAG/ROC2/RBX2 (RNF7) is the second family member of the ROC/Rbx RING component of SCF E3 ubiquitin ligase; it binds Cullin-1 and the SAG-CUL1 complex has ubiquitin ligase activity promoting poly-ubiquitination of E2/CDC34 in vitro. Yeast two-hybrid, co-immunoprecipitation, in vitro ubiquitination assay with E1/E2/CUL1 Molecular cell / Oncogene High 10230407 10851089
1999 ROC1-CUL1 RING-based ubiquitin ligase (with SAG/ROC2 as paralog) can catalyze ubiquitination of IκBα in a phosphorylation-dependent manner in vitro when reconstituted with SCFHOS components, E1, and CDC34. In vitro reconstituted ubiquitination assay with purified components Molecular cell High 10230406
1999 Protein kinase CKII interacts with SAG/RNF7 via the RING-H2 finger motif; specifically, the beta subunit of CKII binds SAG and phosphorylates it in vitro, while the alpha subunit does not interact. Yeast two-hybrid, overlay/direct binding assay, in vitro phosphorylation by recombinant CKII, deletion mutagenesis of SAG Biochemical and biophysical research communications Medium 10512750
2000 The yeast homolog of SAG/RNF7 (ySAG) is essential for cell viability; deletion causes cell death with cell enlargement and abnormal cell cycle profiles. Complementation requires the RING finger domain and ubiquitin ligase activity, confirming that E3 ligase function is required for cell survival. Targeted yeast gene disruption, tetrad analysis, complementation with wild-type vs. RING mutant hSAG, cDNA chip profiling of yeast genome Oncogene High 10851089
2001 SAG/RNF7 promotes S-phase entry and cell growth under serum starvation by inhibiting p27 accumulation through the ubiquitin-proteasome pathway; SAG associates in vivo with SKP2, an F-box protein that promotes p27 ubiquitination. SAG mRNA microinjection into quiescent cells ([3H]-thymidine incorporation), adenoviral overexpression, co-immunoprecipitation of SAG with SKP2, proteasome inhibitor rescue experiment Molecular carcinogenesis Medium 11255262
2001 SAG/RNF7 gene consists of four exons and three introns; a splicing variant (SAG-v) incorporates an additional exon disrupting the RING finger ORF, and SAG-v lacks cullin-1 binding and ubiquitin ligase activity, confirming that the RING domain is required for E3 function. Genomic cloning, RT-PCR, yeast complementation, co-immunoprecipitation with CUL1, in vitro ubiquitination assay DNA and cell biology Medium 11506706
2001 SAG/RNF7 protects neurons in vivo against ischemia/reperfusion brain injury; overexpression via adenoviral delivery reduced infarct area, decreased ROS production and apoptosis; the RING domain mutant was not protective, confirming domain requirement. Adenoviral delivery of wild-type vs. RING mutant SAG into mouse brain, middle cerebral artery occlusion model, infarct measurement, ROS assay Journal of cerebral blood flow and metabolism Medium 11488541
2004 VHL-box proteins specifically interact with Cul2-Rbx1 modules, whereas SOCS-box proteins associate with Cul5-Rbx2 (RNF7). The specificity is determined by the downstream Cul2-box or Cul5-box sequences. RNAi knockdown of Cul5-Rbx2 does not affect VHL-mediated HIF-2α degradation, whereas Cul2-Rbx1 knockdown inhibits it, demonstrating functional distinction between the two Rbx modules. Co-immunoprecipitation of endogenous complexes, domain-swap mutagenesis, siRNA knockdown with HIF-2α degradation readout Genes & development High 15601820
2006 SAG/RNF7 forms part of SAG/ROC-SCF(β-TrCP) E3 ubiquitin ligase that binds pro-caspase-3 via the F-box protein β-TrCP (which recognizes the first 38 amino acids of pro-caspase-3) and promotes its ubiquitination and degradation; siRNA silencing of SAG, ROC1, or β-TrCP increases pro-caspase-3 levels and enhances apoptosis. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, dominant-negative β-TrCP expression, protein half-life assay Neoplasia High 17217622
2007 SAG/RNF7 is a transcriptional target of HIF-1; HIF-1 binds a consensus GCGTG site in the first intron of the SAG gene under hypoxia, and induced SAG in turn promotes VHL-mediated HIF-1α ubiquitination and degradation by forming a complex with CUL-5 and VHL, establishing a negative feedback loop. ChIP assay, luciferase reporter, siRNA silencing, co-immunoprecipitation under hypoxia, HIF-1α protein half-life measurement Oncogene High 17828303
2007 SAG/RNF7 is a novel AP-1 transcriptional target; AP-1 binds two consensus sites in the SAG promoter in vitro and in vivo. SAG reciprocally promotes c-Jun ubiquitination and degradation via Fbw7-SCF, establishing an AP-1/SAG autofeedback loop; SAG siRNA silencing reduced c-Jun polyubiquitination. EMSA, ChIP, luciferase reporter, siRNA knockdown, c-Jun polyubiquitination assay, dominant-negative c-Jun overexpression Cancer research High 17440073
2007 SAG/RNF7 in mouse epidermis targets c-Jun/AP-1 for degradation at early stages of skin carcinogenesis (inhibiting tumor promotion) and targets IκBα for degradation at later stages (activating NF-κB to reduce apoptosis and enhance tumor growth), demonstrating stage-dependent substrate targeting by different F-box proteins. SAG-transgenic mouse model (K14 promoter), AP-1 luciferase reporter mice, Western blotting, DMBA/TPA carcinogenesis model The Journal of cell biology High 17846172
2008 SAG/RNF7 promotes UVB-induced skin hyperplasia by simultaneously targeting c-Jun (pro-tumor promotion) and p27 (anti-proliferative) for degradation in mouse epidermis, but does not affect UVB-induced p53, c-Fos, or cyclin D1. K14-SAG transgenic mice, UVB carcinogenesis model, Western blotting, AP-1 activity assays, DNA synthesis measurement Carcinogenesis Medium 18258608
2008 Cul2-box and Cul5-box sequences determine specificity of BC-box protein assembly with Cul2-Rbx1 versus Cul5-Rbx2 (RNF7) modules; the LPPhiP motif conserved in Cul5-boxes is also compatible with Cul2 interaction; spacer length between BC-box and cullin-box can vary 3–80 amino acids. Purification and co-immunoprecipitation of reconstituted BC-box protein complexes, structure-function domain analysis with mutants The Journal of biological chemistry High 18187417
2009 UBE2F is a NEDD8-conjugating E2 enzyme that specifically pairs with RBX2/RNF7 to neddylate CUL5, while UBE2M pairs with RBX1 to neddylate CUL1-4; structural analysis reveals how E1 accommodates both E2s, establishing that RBX2 selectively activates CUL5-based CRLs through the UBE2F/RBX2 neddylation axis. In vitro neddylation assay, structural analysis of E1-E2 interactions, mutagenesis, cellular neddylation experiments Molecular cell High 19250909
2010 SAG/RNF7 silencing induces apoptosis with accumulation of NOXA; SAG overexpression reduces NOXA levels and shortens NOXA protein half-life, identifying NOXA as a substrate of SAG E3 ubiquitin ligase. In vivo, SAG silencing suppresses xenograft tumor growth. siRNA silencing, protein half-life assay, flow cytometry for apoptosis, caspase-3 assay, in vivo orthotopic xenograft model Clinical cancer research Medium 20103673
2010 Sag/Rbx2 deletion in mouse embryonic stem cells sensitizes them to radiation through increased ROS (including superoxide) and decreased NF-κB activation; IκBα was identified as a direct substrate of SAG-SCF(β-TrCP) E3 ubiquitin ligase, as its degradation is blocked upon Sag elimination. Gene-trap Sag knockout ES cells, clonogenic survival, intracellular ROS measurement, NF-κB reporter, IκBα protein level analysis Free radical biology & medicine High 20638939
2010 SAG/RNF7 as a Tat-fusion protein can be transduced into cells and brain tissue; wild-type but not RING-mutant Tat-SAG protects hippocampal neurons from ischemia-induced death and reduces lipid peroxidation in vivo, confirming that ROS-scavenging via the RING domain is the protective mechanism. Tat-fusion protein transduction, gerbil transient forebrain ischemia model, immunohistochemistry, lipid peroxidation assay Free radical biology & medicine Medium 20100567
2010 CRL network quantitative proteomics shows SAG/RBX2 assembles within distinct CRL5 complexes; network architecture reveals that neddylation inhibition (MLN4924) does not globally reorganize CRL complexes, but adaptor module abundance drives CRL organization. AQUA quantitative proteomics, affinity purification-MS of CRL components, MLN4924 treatment Cell Medium 21145461
2011 SAG/RBX2/RNF7 is an essential RING component of SCF E3 ubiquitin ligase required for embryonic development; Sag knockout mice die at E11.5–12.5 with vascular and neural defects caused by NF1 accumulation and RAS inhibition. NF1 was identified as a physiological substrate of SAG-CUL1-FBXW7 E3 ligase; simultaneous Nf1 deletion partially rescues vascular defects in Sag-null embryos. Sag conditional knockout mice, genetic epistasis (Sag/Nf1 double knockout), ES cell endothelial differentiation assays, teratoma angiogenesis Developmental cell High 22118770
2011 SAG/RBX2 inactivation in mouse embryonic stem cells blocks retinoic acid (RA)-induced differentiation, causing apoptosis instead; in leukemia cells, SAG inhibition with MLN4924 sensitizes to RA-differentiation therapy through accumulation of NOXA and c-JUN substrates of SAG-SCF E3 ligase. Sag-/- ES cells, RA exposure, atomic force microscopy for cell stiffness, MLN4924 treatment of leukemia lines, Western blotting for NOXA/c-JUN PloS one Medium 22110742
2011 DEPTOR is a physiological substrate of SCF(β-TrCP)/SAG E3 ligase; growth factor stimulation activates RSK1/S6K1 to phosphorylate DEPTOR, enabling β-TrCP recognition and SCF-mediated ubiquitination and degradation; this activates mTOR in a positive feedback loop. Protein half-life assay, co-immunoprecipitation, siRNA knockdown, phosphodegron mutagenesis, kinase inhibitor experiments Molecular cell High 22017875 22017876 22017877
2011 HIV-1 Vif hijacks CUL5-ELOB-ELOC-RBX2(RNF7) ubiquitin ligase complex (together with CBF-β) to polyubiquitinate APOBEC3G for degradation; a recombinant six-protein assembly including RBX2 reconstitutes specific APOBEC3G ubiquitination activity. Affinity purification-mass spectrometry, in vitro reconstituted six-protein ubiquitination assay, RNA knockdown, genetic complementation Nature High 22190037
2013 RBX2/RNF7 is required for neocortical and cerebellar neuron positioning; Rbx2 mutation causes DAB1-dependent ectopias via sustained Reelin signaling. SOCS7 is identified as a CRL5-Rbx2 substrate adaptor that promotes ubiquitylation and turnover of DAB1, stopping neuronal migration at target layers; cerebellar development requires Rbx2 through a different adaptor. In utero electroporation, Rbx2 conditional knockout mice, SOCS7 gain-of-function/loss-of-function, DAB1 protein level analysis, epistasis with reelin pathway Developmental cell High 24210661
2013 Sag endothelial deletion causes embryonic lethality at E15.5 with poor vasculogenesis; Sag deletion in endothelial cells inhibits migration, proliferation, and tube formation with p27 accumulation responsible for migration/proliferation suppression; Sag is required for tumor angiogenesis in a B16F10 melanoma model. Tie2-Cre/Sag conditional KO mice, primary EC culture assays (migration, proliferation, tube formation), p27 knockdown rescue, in vivo Matrigel plug and tumor models Oncogene High 24213570
2014 Sag deletion suppresses KrasG12D-driven lung tumorigenesis; SAG knockdown inactivates NF-κB and mTOR pathways and causes accumulation of p21, p27, NOXA, and BIM; growth suppression by SAG knockdown is partially rescued by simultaneous knockdown of p21 or the mTOR inhibitor DEPTOR, establishing these as causal substrates. Lung-specific Sag conditional KO in KrasG12D mice, siRNA epistasis (SAG + p21 or DEPTOR double knockdown), pathway analysis (NF-κB, mTOR) The Journal of clinical investigation High 24430184
2014 SAG/RNF7 promotes ubiquitination of Bax and SARM in macrophages during pathogen challenge, conferring survival advantage; SAG knockdown causes accumulation of pro-apoptotic Bax and SARM, disruption of Bcl-2/Bax balance, cytochrome c release, and caspase-9/-3 activation. SAG knockdown/overexpression in macrophages, PAMP challenge, flow cytometry, Western blotting, cytochrome c release assay Cell death and differentiation Medium 24786833
2014 SOCS2-EloBC-CUL5-RBX2 (RNF7) complex can be reconstituted in vitro in neddylated and unneddylated forms; the complex exists as a monomer (unlike other E3 ligases); affinities of protein-protein interactions within the complex were determined by isothermal titration calorimetry; structural model supported by ion mobility mass spectrometry. Pull-down from human cell lysates, recombinant expression in E. coli and insect cells, SEC-MALS, native MS, ITC, traveling wave ion mobility MS The Journal of biological chemistry High 25247507
2014 NEDD4-1 E3 ubiquitin ligase binds directly via its HECT domain to SAG's C-terminal RING domain and ubiquitylates SAG for proteasomal degradation; SAG bridges NEDD4-1 (via C-terminus) and CUL-5 (via N-terminus) forming a NEDD4-1/SAG/CUL-5 tri-complex; NEDD4-1 overexpression sensitizes cancer cells to apoptosis by reducing SAG levels. Co-immunoprecipitation, protein half-life assay (cycloheximide chase), in vitro binding assay with recombinant proteins, NEDD4-1 overexpression/silencing Oncotarget Medium 25216516
2015 RNF7 (SAG/RBX2) interacts with PCNA in living human cells; this interaction was validated by co-immunoprecipitation from human cell extracts and by interaction analysis using recombinant proteins, suggesting a role for RNF7 in DNA replication or repair. Bimolecular fluorescence complementation (BiFC) screen with human cDNA library, co-immunoprecipitation from cell extracts, recombinant protein interaction analysis Cell cycle Medium 26030842
2015 Erbin is a novel substrate of SAG-β-TrCP E3 ligase; Sag deletion in skin keratinocytes causes Erbin accumulation, which blocks Ras activation of Raf and prevents Nrf2-driven ROS scavenging; knockdown of the Erbin-encoding gene Erbb2ip partially rescues the phenotypes, establishing Erbin as a causal substrate. Sag/Kras double conditional KO keratinocytes, in vivo ubiquitylation assay for Erbin, Erbb2ip genetic rescue, Ras-Raf pathway analysis The Journal of cell biology High 26056141
2016 SAG/RBX2 (RNF7) promotes ubiquitylation and degradation of PHLPP1 and DEPTOR, leading to activation of the PI3K/AKT/mTOR axis in prostate cancer; growth suppression by SAG knockdown is partially rescued by simultaneous knockdown of PHLPP1 or DEPTOR; in vivo ubiquitylation assays confirm both as SAG substrates. siRNA knockdown epistasis, in vivo and in vitro ubiquitylation assays, Sag/Pten double conditional KO prostate mouse model Molecular cancer High 27955654
2016 SAG/RBX2 E3 ligase complex specifically binds E2 enzymes UBCH10 and UBE2S (which mediate K11-linked ubiquitin chains) to ubiquitylate β-TrCP1 via K11-linkage, leading to its degradation; in contrast, RBX1 exclusively binds CDC34 and UBCH5C (K48 linkage). Silencing UBCH10 or UBE2S, but not UBCH5C, causes accumulation of β-TrCP1, establishing it as a physiological SAG-CUL5 substrate. Co-immunoprecipitation of E2 binding, protein half-life assay, siRNA silencing of E2s, SAG-CUL5-βTrCP1 complex co-IP, chemical inducers of SAG Scientific reports High 27910872
2016 SAG/RBX2-dependent neddylation regulates T-cell activation; T-cell-specific Sag knockout mice show phenotypically normal T-cell development but dramatically decreased T-cell activation, proliferation, and effector cytokine release; SAG effects in T cells are associated with increased SOCS expression but not NF-κB translocation. T-cell-specific conditional Sag KO mice, in vitro T-cell stimulation, allogeneic bone marrow transplantation model, MLN4924 pharmacological inhibition, SOCS and NF-κB pathway analysis The American journal of pathology Medium 27543965
2017 RNF7 negatively regulates CARMA2sh (CARD14) signaling by regulating the ubiquitination state of MALT1 and NEMO; RNF7 interacts with CARMA2 (identified by yeast two-hybrid) and suppresses NF-κB activation; psoriasis-associated CARMA2sh mutants escape RNF7 negative regulation. Yeast two-hybrid screen, co-immunoprecipitation, NF-κB reporter assay, ubiquitination assay for MALT1 and NEMO, gain/loss of function with mutants International journal of molecular sciences Medium 29194363
2017 RNF7 knockdown in castration-resistant prostate cancer cells suppresses proliferation, invasiveness, and sensitizes to cisplatin; mechanistically, RNF7 knockdown causes accumulation of p21, p27, and NOXA and inactivates ERK1/2 signaling, suggesting these are functional substrates or downstream effectors. shRNA knockdown, proliferation/invasion assays, clonogenic survival, Western blotting for p21/p27/NOXA/ERK1/2 Scientific reports Medium 28252001
2018 RBX2/RNF7 is required for proper retinal lamination and function; RBX2 depletion causes misposition of rod bipolar cells (via sustained DAB1/Reelin signaling), cone photoreceptors, and Muller glia; SOCS7-CRL5 controls rod bipolar and Muller glia positioning but not cone localization, indicating that RBX2 controls additional CRL5-dependent pathways for cone positioning; RBX2 depletion also reduces ribbon synapses and disrupts cone photoreceptor function. In vivo RBX2 knockdown (shRNA), SOCS7 knockdown, retinal electrophysiology (ERG), immunohistochemistry for cell-layer markers and DAB1 levels Development Medium 29361558
2018 SAG/RBX2 differentially regulates inflammatory responses of macrophages versus neutrophils; in vivo LysM-Cre/Sag myeloid-specific KO mice show increased LPS-induced mortality with decreased cytokine release from Sag-null macrophages but increased cytokine release from Sag-null neutrophils; myeloperoxidase (Mpo) and elastase (Elane) induction by LPS is significantly decreased in Sag-null bone marrow. LysM-Cre conditional Sag KO mice, in vivo LPS challenge, cytokine measurement, gene expression profiling of bone marrow cells Frontiers in immunology Medium 30574150
2020 Gossypol inhibits cullin neddylation by directly binding to SAG-CUL5 and RBX1-CUL1 complexes; CUL5-H572 is a key residue for gossypol binding; cellular treatment with gossypol selectively causes accumulation of NOXA (CUL5 substrate) and MCL1 (CUL1 substrate). AlphaScreen HTS for CUL5 neddylation, biochemical binding assays, mutagenesis of CUL5-H572, cellular substrate accumulation assays Neoplasia Medium 32145688
2022 RNF7 inhibits apoptosis and promotes glycolysis in renal cell carcinoma via ubiquitination of SOCS1, activating JAK/STAT3 signaling; STAT3 activation in turn transcriptionally induces RNF7, creating a feedback loop; RNF7 overexpression also reduces sunitinib sensitivity. siRNA knockdown and overexpression, in vitro apoptosis/glycolysis assays, in vivo xenograft tumor model, STAT3 pathway analysis, ubiquitination of SOCS1 Cellular & molecular biology letters Medium 35562668

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
1987 Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 1488 2825030
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2019 Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 1039 30842662
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2019 Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature 604 30842659
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1999 ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Molecular cell 410 10230407
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2004 VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes & development 409 15601820
2005 A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. The EMBO journal 377 16096638
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2011 Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection. Nature 311 22190037
1999 Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. Molecular cell 304 10230406
2001 NEDD8 recruits E2-ubiquitin to SCF E3 ligase. The EMBO journal 259 11483504
2017 Assembly and Function of Heterotypic Ubiquitin Chains in Cell-Cycle and Protein Quality Control. Cell 255 29033132
2011 DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular cell 245 22017876
1990 Human erythropoietin receptor: cloning, expression, and biologic characterization. Blood 245 2163696
2009 E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Molecular cell 239 19250909
2020 Structural mechanism of cGAS inhibition by the nucleosome. Nature 221 32911482
2011 mTOR drives its own activation via SCF(βTrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Molecular cell 216 22017875
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2005 SOCS2 negatively regulates growth hormone action in vitro and in vivo. The Journal of clinical investigation 194 15690087
2020 Structural basis for the inhibition of cGAS by nucleosomes. Science (New York, N.Y.) 193 32912999
2011 mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Molecular cell 181 22017877
2003 Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proceedings of the National Academy of Sciences of the United States of America 174 12552091
2008 Characterization of Cullin-box sequences that direct recruitment of Cul2-Rbx1 and Cul5-Rbx2 modules to Elongin BC-based ubiquitin ligases. The Journal of biological chemistry 164 18187417
1993 Antibodies to Toxoplasma gondii major surface protein (SAG-1, P30) inhibit infection of host cells and are produced in murine intestine after peroral infection. Journal of immunology (Baltimore, Md. : 1950) 142 7682587
1999 SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents. Molecular and cellular biology 137 10082581
1994 Attachment of Toxoplasma gondii to host cells involves major surface protein, SAG-1 (P30). Experimental parasitology 118 8050521
2014 Ascending SAG neurons control sexual receptivity of Drosophila females. Neuron 115 24991958
2004 Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains. The Journal of biological chemistry 106 15355985
2005 ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes. FEBS letters 98 16325183
2001 Rapid clearance of SAG-2 rabies virus from dogs after oral vaccination. Vaccine 86 11483278
2011 SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Developmental cell 84 22118770
2010 Validation of SAG/RBX2/ROC2 E3 ubiquitin ligase as an anticancer and radiosensitizing target. Clinical cancer research : an official journal of the American Association for Cancer Research 84 20103673
2010 Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in Cancer and as Cancer Targets. Genes & cancer 83 21103004
2014 Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. The Journal of clinical investigation 81 24430184
2006 SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia (New York, N.Y.) 81 17217622
2012 Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase. Protein & cell 80 23136067
2001 SAG/ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions. Antioxidants & redox signaling 79 11554450
2021 Diversity amongst human cortical pyramidal neurons revealed via their sag currents and frequency preferences. Nature communications 74 33941783
2007 SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradation. Oncogene 71 17828303
2003 Accumulation, assimilation and growth inhibition of copper on freshwater alga (Scenedesmus subspicatus 86.81 SAG) in the presence of EDTA and fulvic acid. Aquatic toxicology (Amsterdam, Netherlands) 67 12711412
2002 Clostridium septicum alpha-toxin is active against the parasitic protozoan Toxoplasma gondii and targets members of the SAG family of glycosylphosphatidylinositol-anchored surface proteins. Infection and immunity 67 12117945
2001 Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 61 11488541
2000 Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation. Oncogene 61 10851089
2007 SAG/ROC2/Rbx2 is a novel activator protein-1 target that promotes c-Jun degradation and inhibits 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic transformation. Cancer research 59 17440073
2003 DNA vaccination with the immunodominant tachyzoite surface antigen (SAG-1) protects against adult acquired Toxoplasma gondii infection but does not prevent maternofoetal transmission. Vaccine 58 12798622
2018 Genome sequences of Chlorella sorokiniana UTEX 1602 and Micractinium conductrix SAG 241.80: implications to maltose excretion by a green alga. The Plant journal : for cell and molecular biology 54 29178410
2010 Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani. British journal of clinical pharmacology 53 20840452
2005 Binding of the global response regulator protein CovR to the sag promoter of Streptococcus pyogenes reveals a new mode of CovR-DNA interaction. The Journal of biological chemistry 52 16174772
2003 Vaccination with Toxoplasma gondii SAG-1 protein is protective against congenital toxoplasmosis in BALB/c mice but not in CBA/J mice. Infection and immunity 52 14573684
1999 Expression, purification, and biochemical characterization of SAG, a ring finger redox-sensitive protein. Free radical biology & medicine 52 10443936
2007 SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IkappaB-alpha/NF-kappaB. The Journal of cell biology 51 17846172
2004 Identification of a sporozoite-specific member of the Toxoplasma SAG superfamily via genetic complementation. Molecular microbiology 50 15049813
2016 Depletion of SAG/RBX2 E3 ubiquitin ligase suppresses prostate tumorigenesis via inactivation of the PI3K/AKT/mTOR axis. Molecular cancer 45 27955654
2013 Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors. Developmental cell 45 24210661
1977 Identification of lymphocytes in percutaneous liver biopsy cores. Different T:B cell ratio in HB sAg-positive and -negative hepatitis. Gastroenterology 44 323096
2011 The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway. Molecular immunology 43 21920605
2001 Elevated expression of SAG/ROC2/Rbx2/Hrt2 in human colon carcinomas: SAG does not induce neoplastic transformation, but antisense SAG transfection inhibits tumor cell growth. Molecular carcinogenesis 41 11255265
1994 Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes. Genomics 41 7695743
1993 Mouse mammary tumor virus-induced tumorigenesis in sag transgenic mice: a laboratory model of natural selection. Journal of virology 40 8230492
1991 Comparison of the effects of SAG-M and whole-blood transfusions on postoperative suppression of delayed hypersensitivity. Canadian journal of surgery. Journal canadien de chirurgie 40 2025803
2022 How clear is our current view on microbial dark matter? (Re-)assessing public MAG & SAG datasets with MDMcleaner. Nucleic acids research 39 35536293
1992 Cloning and expression of SAG: a novel marker of cellular senescence. Experimental cell research 39 1544376
2012 Comparing the effect of IL-12 genetic adjuvant and alum non-genetic adjuvant on the efficiency of the cocktail DNA vaccine containing plasmids encoding SAG-1 and ROP-2 of Toxoplasma gondii. Parasitology research 37 22350714
2005 Sarcocystis neurona merozoites express a family of immunogenic surface antigens that are orthologues of the Toxoplasma gondii surface antigens (SAGs) and SAG-related sequences. Infection and immunity 37 15664946
2016 Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons. Journal of biological rhythms 36 27658900
2016 SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation. Scientific reports 36 27910872
2010 Transduced Tat-SAG fusion protein protects against oxidative stress and brain ischemic insult. Free radical biology & medicine 36 20100567
2006 Effects of cytokinin production under two SAG promoters on senescence and development of tomato plants. Plant biology (Stuttgart, Germany) 36 16883480
2010 Disruption of Sag/Rbx2/Roc2 induces radiosensitization by increasing ROS levels and blocking NF-kappaB activation in mouse embryonic stem cells. Free radical biology & medicine 34 20638939
2001 Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: association with inhibition of p27 accumulation. Molecular carcinogenesis 34 11255262
2015 Erbin is a novel substrate of the Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. The Journal of cell biology 33 26056141
2011 Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid. PloS one 33 22110742
2008 SAG/ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27. Carcinogenesis 33 18258608
2007 SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling. Neuroscience letters 33 17240529
1999 Alterations of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection. Carcinogenesis 32 10506102
2014 Ubiquitination by SAG regulates macrophage survival/death and immune response during infection. Cell death and differentiation 31 24786833
2004 gp340 (SAG) binds to the V3 sequence of gp120 important for chemokine receptor interaction. AIDS research and human retroviruses 31 15242536
1999 Sag during unfused tetanic contractions in rat triceps surae motor units. Journal of neurophysiology 31 10368385
2009 Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-gamma to IL-10 ratio. Experimental parasitology 30 19422069
2017 A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States. Investigative ophthalmology & visual science 29 28549094
2016 SAG/Rbx2-Dependent Neddylation Regulates T-Cell Responses. The American journal of pathology 29 27543965
2014 SAG/RBX2 is a novel substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. Oncotarget 29 25216516
2013 Novel twin streptolysin S-like peptides encoded in the sag operon homologue of beta-hemolytic Streptococcus anginosus. Journal of bacteriology 29 23292771
2003 SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes. Journal of molecular and cellular cardiology 29 12676540
1999 Erythrocytes stored in CPD SAG-mannitol: evaluation of their deformability. Clinical hemorheology and microcirculation 29 10711766
2020 Gossypol inhibits cullin neddylation by targeting SAG-CUL5 and RBX1-CUL1 complexes. Neoplasia (New York, N.Y.) 28 32145688
2013 Endothelial deletion of Sag/Rbx2/Roc2 E3 ubiquitin ligase causes embryonic lethality and blocks tumor angiogenesis. Oncogene 28 24213570
2014 Biophysical studies on interactions and assembly of full-size E3 ubiquitin ligase: suppressor of cytokine signaling 2 (SOCS2)-elongin BC-cullin 5-ring box protein 2 (RBX2). The Journal of biological chemistry 27 25505247
2011 Synthesis of Ag(2) S-Ag nanoprisms and their use as DNA hybridization probes. Small (Weinheim an der Bergstrasse, Germany) 27 21538868
2013 Arabidopsis SAG protein containing the MDN1 domain participates in seed germination and seedling development by negatively regulating ABI3 and ABI5. Journal of experimental botany 25 24163287
2001 SAG/ROC2/Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a splicing variant, and two family pseudogenes. DNA and cell biology 25 11506706
1996 Exogenous mouse mammary tumor virus (MMTV) infection induces endogenous MMTV sag expression. Virology 25 8560758
1990 Assignment of the S-antigen gene (SAG) to human chromosome 2q24-q37. Genomics 25 2335355
2014 Understanding the effects of gamma-irradiation on potassium levels in red cell concentrates stored in SAG-M for neonatal red cell transfusion. Vox sanguinis 24 25195496
2013 Size does not always matter: Ts65Dn Down syndrome mice show cerebellum-dependent motor learning deficits that cannot be rescued by postnatal SAG treatment. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 24068809
2013 Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani. PLoS neglected tropical diseases 22 24340105
2020 SA/G hydrogel containing hCAP-18/LL-37-engineered WJ-MSCs-derived conditioned medium promoted wound healing in rat model of excision injury. Life sciences 21 32891611
2015 A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells. Cell cycle (Georgetown, Tex.) 21 26030842
2002 Increased non-transferrin bound iron in plasma-depleted SAG-M red blood cell units. Vox sanguinis 21 11952985
1999 Protein kinase CKII interacts with and phosphorylates the SAG protein containing ring-H2 finger motif. Biochemical and biophysical research communications 21 10512750
1995 Differential human T cell-dependent B cell differentiation induced by staphylococcal superantigens (SAg). Regulatory role for SAg-dependent B cell cytolysis. Journal of immunology (Baltimore, Md. : 1950) 21 7636237
2022 RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop. Cellular & molecular biology letters 20 35562668
2018 Baseline characteristics and patterns of care in testicular cancer patients: first data from the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS). Swiss medical weekly 20 30044478
2014 Co-administration of glycyrrhizic acid with the antileishmanial drug sodium antimony gluconate (SAG) cures SAG-resistant visceral leishmaniasis. International journal of antimicrobial agents 19 25600891
2020 Long non-coding RNA RNF7 promotes the cardiac fibrosis in rat model via miR-543/THBS1 axis and TGFβ1 activation. Aging 18 31913855
2020 Sonic Hedgehog Signaling Agonist (SAG) Triggers BDNF Secretion and Promotes the Maturation of GABAergic Networks in the Postnatal Rat Hippocampus. Frontiers in cellular neuroscience 17 32425757
2018 SAG/RBX2 E3 Ubiquitin Ligase Differentially Regulates Inflammatory Responses of Myeloid Cell Subsets. Frontiers in immunology 17 30574150
2017 PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population. Journal of gastrointestinal and liver diseases : JGLD 17 28338112
2017 Early γ-irradiation and subsequent storage of red cells in SAG-M additive solution potentiate energy imbalance, microvesiculation and susceptibility to stress-induced apoptotic cell death. Vox sanguinis 17 28378415
2009 Identification of genetic markers in sodium antimony gluconate (SAG) sensitive and resistant Indian clinical isolates of Leishmania donovani through amplified fragment length polymorphism (AFLP). Acta tropica 17 19283900
1992 SAG: a Schwann cell membrane glycoprotein. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 1376775
2018 RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion. Development (Cambridge, England) 16 29361558
2018 Multilocus characterization of Sarcocystis falcatula-related organisms isolated in Brazil supports genetic admixture of high diverse SAG alleles among the isolates. Experimental parasitology 16 29522766
2011 Macular Dysfunction in Oguchi Disease with the Frequent Mutation 1147delA in the SAG Gene. Ophthalmic research 16 21447990
2009 Nonhemolytic Streptococcus pyogenes isolates that lack large regions of the sag operon mediating streptolysin S production. Journal of clinical microbiology 16 20018818
2005 The effect of pre-storage cooling on 2,3-DPG levels in red cells stored in SAG-M. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 16 16109505
2017 RNF7 knockdown inhibits prostate cancer tumorigenesis by inactivation of ERK1/2 pathway. Scientific reports 15 28252001
2016 Resolving the phylogenetic relationship between Chlamydomonas sp. UWO 241 and Chlamydomonas raudensis sag 49.72 (Chlorophyceae) with nuclear and plastid DNA sequences. Journal of phycology 15 27037594
2012 Leishmania donovani: CD2 biased immune response skews the SAG mediated therapy for a predominant Th1 response in experimental infection. Experimental parasitology 15 22580024
2022 The smoothened agonist SAG reduces mitochondrial dysfunction and neurotoxicity of frataxin-deficient astrocytes. Journal of neuroinflammation 14 35413853
2017 The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling. International journal of molecular sciences 14 29194363