Affinage

SOCS6

Suppressor of cytokine signaling 6 · UniProt O14544

Round 2 corrected
Length
535 aa
Mass
59.5 kDa
Annotated
2026-04-28
122 papers in source corpus 25 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOCS6 is an SH2-domain-containing adaptor that recruits the Elongin BC–Cullin 5 E3 ubiquitin ligase complex via its SOCS box to target phosphotyrosine-bearing substrates for ubiquitin-proteasomal degradation, thereby negatively regulating receptor tyrosine kinase signaling, cytokine-JAK-STAT signaling, and T cell activation. Its SH2 domain preferentially recognizes pY+1 Val motifs and binds specific phosphotyrosines on c-KIT (pY568), Flt3 (pY591/pY919), the insulin receptor, p56lck, DAB1, and SLC7A11, promoting their ubiquitination and degradation to attenuate ERK1/2 and STAT3 signaling (PMID:12052866, PMID:21030588, PMID:22952242, PMID:20007709, PMID:41061872). SOCS6 also localizes to mitochondria where it complexes with DRP1 and PGAM5 to promote mitochondrial fission and intrinsic apoptosis (PMID:22955947). Combined loss of SOCS6 and SOCS7 in mice causes cortical layer inversion resembling the reeler phenotype, establishing SOCS6 as a required terminator of Reelin–DAB1 signaling during cortical development (PMID:26503265).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    The first mechanistic link between SOCS6 and insulin signaling was established, showing that SOCS6 binds the insulin receptor after stimulation and inhibits downstream ERK1/2 and PKB activation without blocking receptor autophosphorylation, placing SOCS6 as a post-receptor negative regulator.

    Evidence Co-immunoprecipitation in HepG2 and rat hepatoma cells with in vitro kinase and in vivo signaling assays

    PMID:11342531

    Open questions at the time
    • Mechanism of SOCS6 recruitment to the IR (specific phosphotyrosine site) was undefined
    • Ubiquitination of the IR by SOCS6 was not tested
  2. 2002 High

    Biochemical characterization revealed that SOCS6 binds Elongin BC through its SOCS box (establishing E3 ligase adaptor function) and that its SH2 domain selects phosphopeptides with pY+1 Val, defining the substrate-recognition logic; knockout mice showed a growth defect but no overt metabolic phenotype.

    Evidence Phosphopeptide binding specificity assays, Co-IP with Elongins, SOCS6-knockout mouse phenotyping

    PMID:12052866

    Open questions at the time
    • No direct ubiquitination substrate was identified
    • The mild knockout phenotype suggested functional redundancy with SOCS7
  3. 2004 High

    SOCS6 was mapped to specific RTK substrates: it binds c-KIT at pY567 and selectively suppresses KIT-driven ERK and p38 signaling, while in a parallel study SOCS6 was shown to modulate PI3K signaling by sequestering monomeric p85 and improving glucose metabolism in transgenic mice.

    Evidence KIT phosphotyrosine mutagenesis, SOCS6-transgenic mice, Co-IP for p85 interaction, proteasome inhibitor experiments

    PMID:14707129 PMID:15123678

    Open questions at the time
    • Whether SOCS6 directly ubiquitinates KIT was not shown at this stage
    • The distinct roles of SOCS6 in RTK versus insulin signaling remained unresolved
  4. 2006 Medium

    SOCS6 protein stability was shown to be positively regulated by a PKCδ–ERK pathway, and an alternative E3 ligase partner (HOIL-1) was found to interact with and stabilize SOCS6, expanding the regulatory network beyond the canonical Elongin BC–Cullin 5 complex.

    Evidence Pharmacological inhibitors in HEK293T/MCF7 cells; Co-IP and ubiquitination assays for HOIL-1 interaction

    PMID:16643902 PMID:17210122

    Open questions at the time
    • Physiological significance of the HOIL-1 interaction was not demonstrated in vivo
    • Whether PKCδ-ERK stabilization creates a feedback loop on SOCS6 target turnover was not tested
  5. 2007 Medium

    Domain-mapping studies revealed that SOCS6 shuttles between the nucleus and cytoplasm, with N-terminal residues 1–210 directing nuclear entry and the C-terminal region required for reducing nuclear STAT3 levels, indicating SOCS6 can regulate transcription factor abundance in the nucleus.

    Evidence GFP-truncation constructs, confocal microscopy, subcellular fractionation in transfected cells

    PMID:17603019

    Open questions at the time
    • Whether SOCS6 ubiquitinates nuclear STAT3 directly was not tested
    • Nuclear function of SOCS6 was not validated in primary cells
  6. 2009 High

    SOCS6 was identified as a negative regulator of T cell activation: it binds constitutively active p56lck, promotes its ubiquitination and proteasomal degradation at the immunological synapse, and suppresses IL-2 promoter activity, establishing SOCS6 as a checkpoint in TCR signaling.

    Evidence Yeast two-hybrid, Co-IP, confocal microscopy, ubiquitination assay, IL-2 luciferase reporter in Jurkat T cells

    PMID:20007709

    Open questions at the time
    • In vivo T cell phenotype of SOCS6 loss was not examined
    • Whether SOCS6 targets wild-type lck under physiological TCR stimulation remained unclear
  7. 2010 High

    A 1.45 Å crystal structure of the SOCS6 SH2 domain bound to c-KIT pY568 peptide revealed the molecular basis for substrate selectivity, including an extended binding groove to pY+6 and a large BG loop insertion, while functional assays confirmed SOCS6 E3 ligase activity toward c-KIT in cells.

    Evidence X-ray crystallography, surface plasmon resonance (Kd = 0.3 μM), in-cell ubiquitination and turnover assays

    PMID:21030588

    Open questions at the time
    • Full-length SOCS6 structure was not determined
    • The structural basis for the Elongin BC–Cullin 5 interface of SOCS6 remained unresolved
  8. 2012 High

    Two major advances broadened SOCS6 biology: (1) SOCS6 was shown to bind Flt3 at pY591/pY919, promoting its ubiquitination, internalization, and degradation to suppress oncogenic Flt3-ITD–driven proliferation; (2) SOCS6 was found to target mitochondria, complex with DRP1 and PGAM5, attenuate DRP1 phosphorylation, and promote mitochondrial fission coupled to intrinsic apoptosis.

    Evidence Phosphopeptide fishing and multiple functional assays in Ba/F3 and UT-7 cells (Flt3); Co-IP, mutagenesis, confocal microscopy, Bax oligomerization assays (mitochondrial fission)

    PMID:22952242 PMID:22955947

    Open questions at the time
    • Whether SOCS6 ubiquitinates DRP1 or PGAM5 was not established
    • The relative contribution of mitochondrial versus RTK functions to SOCS6-dependent apoptosis was unclear
  9. 2017 High

    Genetic evidence in SOCS6/SOCS7 double-knockout mice demonstrated that SOCS6 is essential for terminating Reelin signaling during cortical development by promoting DAB1 degradation; loss of both SOCS proteins phenocopied the reeler cortical inversion.

    Evidence Single and double knockout mice, ex vivo SH2-domain binding assays, DAB1 mutagenesis, immunofluorescence

    PMID:26503265

    Open questions at the time
    • The individual contributions of SOCS6 versus SOCS7 to DAB1 degradation were not fully separable
    • Downstream transcriptional consequences of sustained DAB1 in cortical neurons were not defined
  10. 2021 High

    In cancer contexts, SOCS6 was shown to ubiquitinate and degrade c-KIT to promote radiosensitivity in esophageal squamous cell carcinoma, reducing cancer stem cell populations in a partially p53-dependent manner.

    Evidence Co-IP, ubiquitination assay, flow cytometry, sphere formation, xenograft tumors

    PMID:33689885 PMID:33712005

    Open questions at the time
    • Whether SOCS6 directly interacts with p53 or is transcriptionally induced was not fully delineated
    • Applicability to other c-KIT-driven cancers was not tested
  11. 2025 Medium

    Recent work expanded SOCS6 substrates and regulatory inputs: SOCS6 was shown to ubiquitinate SLC7A11 (xCT) to drive ferroptosis in ovarian cancer, and FTO-mediated m6A demethylation of SOCS6 mRNA was found to reduce SOCS6 expression, linking epitranscriptomic regulation to inflammatory signaling in keratinocytes.

    Evidence Co-IP and ubiquitination assay for SLC7A11, GSH/ROS/Fe²⁺ measurements, xenograft; Me-RIP, mRNA stability assays, in vivo FTO knockdown for epitranscriptomic regulation

    PMID:41061872 PMID:41644088

    Open questions at the time
    • The specific SOCS6 SH2-binding phosphotyrosine on SLC7A11 is not identified
    • Whether FTO-SOCS6 regulation operates beyond keratinocytes is unknown
    • Independent replication of SLC7A11 as a direct SOCS6 substrate is needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of SOCS6 in complex with Elongin BC–Cullin 5, the extent of functional redundancy with SOCS7, the in vivo immunological phenotype of SOCS6 loss in T cells, and how the nuclear, mitochondrial, and cytoplasmic functions of SOCS6 are coordinated.
  • No full-length SOCS6-Elongin BC-Cullin 5 structure exists
  • In vivo T cell-specific SOCS6 knockout phenotype not reported
  • Coordination of subcellular pools of SOCS6 is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005829 cytosol 3 GO:0005739 mitochondrion 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2 R-HSA-1266738 Developmental Biology 1
Partners
DAB1DRP1FLT3KITLCKPGAM5SLC7A11TCEB1
Complex memberships
DRP1–PGAM5 mitochondrial fission complexElongin BC–Cullin 5 (CRL5) E3 ligase complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SOCS6 binds to elongins B and C through its SOCS box, suggesting it acts as an E3 ubiquitin ligase. The SH2 domains of SOCS6 (and SOCS7) preferentially bind phosphopeptides with valine at pY+1 and hydrophobic residues at pY+2/+3. SOCS6 interacts with a protein complex consisting of IRS-4, IRS-2, and the p85 regulatory subunit of PI3K. SOCS6-knockout mice weigh ~10% less than wild-type littermates. Biochemical binding assays, phosphopeptide binding specificity studies, Co-IP, gene knockout mouse model Molecular and cellular biology High 12052866
2001 SOCS-1 and SOCS-6 interact with the insulin receptor (IR) in hepatoma cells; SOCS-6 association with the IR requires insulin treatment. Neither protein inhibits IR autophosphorylation, but both inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro, suggesting a mechanism for cytokine-induced insulin resistance. Co-immunoprecipitation in HepG2/rat hepatoma cells, in vitro IR kinase assay, in vivo signaling assays The Journal of biological chemistry High 11342531
2004 SOCS6 binds directly to KIT receptor at phosphotyrosine 567 in the juxtamembrane domain. Ectopic SOCS6 expression decreases SCF-induced cell proliferation and reduces SCF-induced activation of ERK1/2 and p38, but not AKT or STATs, identifying SOCS6 as a selective negative regulator of KIT-MAPK signaling. KIT mutant constructs and synthetic peptides, stable cell line expression, Western blot signaling assays The Journal of biological chemistry High 14707129
2004 Insulin stimulation induces SOCS-6 expression and interaction of SOCS-6 with the monomeric p85 subunit of class-Ia PI3K (but not p85/p110 dimers). SOCS-6 transgenic mice show improved glucose metabolism and potentiated Akt phosphorylation. SOCS-6 protein is degraded via the proteasome after insulin induction, while SOCS-6-associated p85 is not degraded. SOCS-6 transgenic mice, Co-IP, Western blot, proteasome inhibitor experiments, insulin stimulation assays The Journal of biological chemistry High 15123678
2006 The E3 ubiquitin ligase HOIL-1 interacts with SOCS6 via its Ubl domain binding to the SH2 and SOCS-box domains of SOCS6. HOIL-1 expression stabilizes SOCS6 and induces ubiquitination and degradation of SOCS6-associated proteins, indicating SOCS proteins can interact with E3 ubiquitin ligases beyond the canonical Elongin BC complex. Co-IP, ubiquitination assays, domain mapping with deletion mutants FEBS letters Medium 16643902
2006 SOCS6 protein stability is increased by PMA treatment through a PKCδ→ERK pathway. The N-terminal region of SOCS6 is required for this stabilization. Insulin and PDGF also increase endogenous SOCS6 stability through ERK activation. Ectopic expression in HEK293T and MCF7 cells, pharmacological inhibitors of PKC and ERK, Western blot stability assays Biochemical and biophysical research communications Medium 17210122
2007 SOCS6 localizes to both nucleus and cytoplasm; nuclear localization is dependent on amino acids 1–210 in the N-terminal region. The C-terminal region of SOCS6 is required for decreasing nuclear Stat3 protein levels, identifying two functionally distinct domains. GFP-tagged truncation constructs, confocal microscopy, subcellular fractionation, Western blot Biochemical and biophysical research communications Medium 17603019
2009 SOCS6 acts as a negative regulator of T cell activation by binding to the kinase domain of active p56lck (identified via yeast two-hybrid). SOCS6 binds specifically to the constitutively active F505 form of p56lck but not wild-type. Upon TCR stimulation, SOCS6 is recruited to the immunological synapse, promotes p56lck ubiquitination and proteasomal degradation, and represses TCR-dependent IL-2 promoter activity. Yeast two-hybrid, Co-IP, confocal microscopy, ubiquitination assay, IL-2 reporter assay in Jurkat T cells The Journal of biological chemistry High 20007709
2009 SOCS6 is down-regulated in gastric cancer via allelic loss and promoter hypermethylation. Ectopic SOCS6 expression suppresses cell growth and colony formation and triggers the intrinsic apoptotic pathway, accompanied by decreased mitochondrial membrane potential. Methylation analysis, ectopic expression, colony formation assay, mitochondrial membrane potential assay, apoptosis assay Cancer letters Medium 19646809
2010 Crystal structure of the SOCS6 SH2 domain bound to the c-KIT pY568 peptide (residues 564–574) at 1.45 Å resolution reveals a highly complementary interface with high affinity (Kd = 0.3 μM). The SH2 binding pocket extends to pY+6 and a large BG loop insertion contributes significantly to substrate specificity. SOCS6 has E3 ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells. X-ray crystallography, surface plasmon resonance (binding affinity), ubiquitination assay, cell-based KIT turnover assay The Journal of biological chemistry High 21030588
2012 SOCS6 promotes mitochondrial fission by forming a complex with DRP1 and the mitochondrial phosphatase PGAM5, attenuating DRP1 phosphorylation and promoting DRP1 mitochondrial translocation. SOCS6 targets to mitochondria and induces mitochondrial fragmentation, leading to intrinsic apoptosis (Bax conformational change, mitochondrial targeting, oligomerization). Mutation analysis shows SOCS6-mediated apoptosis is coupled to its ability to induce mitochondrial fission. Lentiviral knockdown, Co-IP, mutagenesis, confocal microscopy, Bax oligomerization assay, DRP1 phosphorylation/localization assays Cell death and differentiation High 22955947
2012 SOCS6 binds directly to phosphotyrosines 591 and 919 of Flt3 upon ligand stimulation (identified by phosphopeptide fishing). SOCS6 enhances Flt3 ubiquitination, internalization, and degradation, and reduces Erk1/2 (but not Akt) activation. SOCS6 absence promotes cell proliferation induced by oncogenic Flt3-ITD. SOCS6 itself undergoes tyrosine phosphorylation upon Flt3 stimulation. Phosphopeptide fishing, Co-IP, ubiquitination assay, receptor internalization/degradation assay, stable Ba/F3 and UT-7 cell lines, Western blot signaling The Journal of biological chemistry High 22952242
2014 SOCS6 selectively suppresses receptor tyrosine kinase signaling. SOCS6 negatively regulates RTK signaling by promoting ubiquitination-mediated receptor degradation and induces apoptosis by targeting mitochondrial proteins, functioning as an E3 ubiquitin ligase adaptor through its SOCS box with Elongin BC and as an SH2-domain-containing substrate recognition module. Review/synthesis integrating previous Co-IP, ubiquitination, and functional data Tumour biology Medium 25172101
2017 Combined loss of SOCS6 and SOCS7 in mice recapitulates the cortical layer inversion seen in reeler mice (lacking Reelin), with dramatic increase in DAB1 in the cortex. SOCS6 and SOCS7 SH2 domains bind DAB1 ex vivo; DAB1 mutation diminishes binding and protects from SOCS6-mediated degradation. Phosphorylated DAB1 is elevated in SOCS6/7 double-knockout cortical neurons. Thus SOCS6 terminates Reelin signaling by promoting DAB1 degradation. Single and double knockout mice, ex vivo SH2 domain binding assays, DAB1 mutagenesis, immunofluorescence, Western blot Cerebral cortex High 26503265
2021 SOCS6 promotes radiosensitivity in esophageal squamous cell carcinoma (ESCC) by ubiquitinating and degrading c-Kit. SOCS6 and c-Kit colocalize in the cytoplasm. SOCS6 overexpression decreases cancer stem cell populations (CD271+, CD24low/CD44high), and inhibits tumor growth in xenograft models. SOCS6 deficiency increases radioresistance by enhancing G2/M arrest, DNA damage repair, and inhibiting apoptosis; SOCS6 transcription is partially p53-dependent. CoIP, ubiquitination assay, immunofluorescence/confocal microscopy, flow cytometry, sphere formation, xenograft, transcriptome sequencing Cancer cell international / Biochemical and biophysical research communications High 33689885 33712005
2022 SOCS6 promotes mitochondrial fission and cardiomyocyte apoptosis in hypoxia/reoxygenation injury. SOCS6 is a direct target of miR-19b; Quaking (QK) RNA-binding protein regulates miR-19b expression, placing QK upstream of miR-19b/SOCS6 in cardiomyocyte I/R injury. SOCS6 inhibition by RNA interference attenuates H/R-induced mitochondrial fission and apoptosis. Dual-luciferase reporter assay, RNA interference, Western blot, in vivo mouse I/R model, apoptosis assays Oxidative medicine and cellular longevity Medium 35126805
2020 The BC-box motif of SOCS6 (sequence SLQYLCRFVI, the elongin BC binding site) is sufficient to promote GABAergic neuronal differentiation of epidermal stem cells via ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Intracellular peptide delivery, Western blot for JAK2 ubiquitination, JAK2/STAT3 pathway readouts, in vivo transplantation in ischemic rat brain International journal of molecular sciences Medium 32668737
2025 The N6-methyladenosine demethylase FTO binds and demethylates m6A modifications within the coding sequence of SOCS6 mRNA, reducing SOCS6 mRNA stability and protein expression. This FTO/SOCS6-m6A axis activates inflammatory programs (IL-1β, S100A8, S100A9) in keratinocytes, linking obesity-associated FTO upregulation to atopic dermatitis pathology. Transcriptomic and epitranscriptomic sequencing, Me-RIP assay, Western blot, RNA stability assays, topical FTO knockdown in vivo The Journal of investigative dermatology Medium 41644088
2025 SOCS6 promotes ubiquitin-proteasomal degradation of SLC7A11 (xCT), reducing intracellular glutathione and augmenting ROS and Fe2+ accumulation to drive ferroptosis in ovarian cancer cells. SOCS6 also suppresses de novo fatty acid synthesis by downregulating FASN and ACC enzymes. Co-IP, ubiquitination assay, GSH/ROS/Fe2+ measurements, lipid synthesis enzyme Western blot, xenograft model Gene Medium 41061872
2025 LncRNA CASC2 (from retinal pigment epithelial cell exosomes) stabilizes SOCS6 mRNA via recruitment of the RNA-binding protein U2AF2, thereby inhibiting M1 macrophage polarization and promoting M2 polarization. This CASC2/U2AF2/SOCS6 axis attenuates diabetic retinopathy in vitro and in vivo. RNA immunoprecipitation (RIP), dual-luciferase reporter assay, Western blot, flow cytometry for macrophage polarization, in vivo diabetic rat model Diabetic medicine Medium 40065730
2014 miR-155 directly targets the SOCS6 3'-UTR, repressing SOCS6 protein and mRNA; sustained miR-155 overexpression activates STAT3 and promotes tamoxifen resistance in breast cancer. Reintroduction of SOCS6 cDNA lacking the 3'-UTR abrogates miR-155-induced cell survival, establishing a miR-155/SOCS6/STAT3 axis. Luciferase reporter assay, Western blot, miRNA mimic/inhibitor transfection, SOCS6 rescue experiment American journal of translational research Medium 26692956
2013 miR-424-5p directly suppresses SOCS6 expression in pancreatic cancer (confirmed by luciferase reporter assay) and activates the ERK1/2 signaling pathway downstream of SOCS6 suppression. Luciferase reporter assay, qRT-PCR, Western blot, miR-424-5p inhibition and SOCS6 overexpression functional studies Pathology oncology research Medium 23653113
2017 miR-494-3p overexpression in primary myelofibrosis HSPCs promotes megakaryocytopoiesis by targeting SOCS6 (confirmed by luciferase assay); SOCS6 silencing in normal HSPCs mimics this phenotype and activates STAT3. miR-494-3p inhibition in PMF HSPCs upregulates SOCS6 and impairs aberrant megakaryocyte differentiation. Luciferase reporter assay, Western blot, gene expression profiling, SOCS6 siRNA knockdown, miRNA inhibition in patient-derived HSPCs Oncotarget Medium 28423484
2024 Japanese eel AjSOCS6 (with conserved SH2 and SOCS box domains) localizes to the cytoplasm and negatively regulates both MyD88-dependent NF-κB signaling and the type I IFN signaling pathway. Co-transfection with AjMyD88 reduced NF-κB luciferase activity, and knockdown upregulated immune gene expression in vivo. Subcellular localization (fluorescence), NF-κB luciferase reporter assay, co-transfection with MyD88, siRNA knockdown in vitro and in vivo Fish & shellfish immunology Medium 39276815

Source papers

Stage 0 corpus · 122 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2008 Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. The New England journal of medicine 743 18204098
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
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
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
2002 The SOCS box: a tale of destruction and degradation. Trends in biochemical sciences 360 12076535
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
1997 Cloning and characterization of novel CIS family genes. Biochemical and biophysical research communications 210 9344848
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2001 Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance. The Journal of biological chemistry 200 11342531
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2016 MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN. Oncotarget 156 27811366
2014 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. Nature methods 131 24658140
2002 SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Molecular and cellular biology 126 12052866
2014 In silico prediction of physical protein interactions and characterization of interactome orphans. Nature methods 112 25402006
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2014 Opposing activities of the Ras and Hippo pathways converge on regulation of YAP protein turnover. The EMBO journal 105 25180228
2013 A Y2H-seq approach defines the human protein methyltransferase interactome. Nature methods 93 23455924
2013 MicroRNA-424-5p suppresses the expression of SOCS6 in pancreatic cancer. Pathology oncology research : POR 89 23653113
2015 MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. American journal of translational research 88 26692956
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2004 Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor signaling. The Journal of biological chemistry 72 14707129
2006 The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. The Journal of pharmacology and experimental therapeutics 71 17099072
2014 miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells. FEBS letters 67 24801601
2012 Suppressor of cytokine signaling 6 (SOCS6) promotes mitochondrial fission via regulating DRP1 translocation. Cell death and differentiation 65 22955947
2012 Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. The Journal of biological chemistry 63 22952242
2013 Reduced expression of SOCS2 and SOCS6 in hepatocellular carcinoma correlates with aggressive tumor progression and poor prognosis. Molecular and cellular biochemistry 62 23475171
2015 Phospho-tyrosine dependent protein-protein interaction network. Molecular systems biology 61 25814554
2009 SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation. Cancer letters 61 19646809
2014 Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer. British journal of cancer 59 25025962
2010 Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. The Journal of biological chemistry 58 21030588
2019 ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection. Cell host & microbe 57 31253590
2012 Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors. PloS one 56 22973453
2004 Insulin induces SOCS-6 expression and its binding to the p85 monomer of phosphoinositide 3-kinase, resulting in improvement in glucose metabolism. The Journal of biological chemistry 55 15123678
2019 Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway. Artificial cells, nanomedicine, and biotechnology 54 31144533
2006 In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in the rat. The Journal of pharmacology and experimental therapeutics 49 16443723
2015 MiR-301a promotes colorectal cancer cell growth and invasion by directly targeting SOCS6. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 25591765
2015 MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells. European review for medical and pharmacological sciences 48 26400524
2020 miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6. Oxidative medicine and cellular longevity 47 32587662
2013 Rbx2 regulates neuronal migration through different cullin 5-RING ligase adaptors. Developmental cell 45 24210661
1995 (+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7- bc][2,6]-naphthyridine: a 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity. Journal of medicinal chemistry 43 7837236
2014 SOCS6 is a selective suppressor of receptor tyrosine kinase signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 25172101
2007 The skeletal rearrangement of gold- and platinum-catalyzed cycloisomerization of cis-4,6-dien-1-yn-3-ols: pinacol rearrangement and formation of bicyclo[4.1.0]heptenone and reorganized styrene derivatives. Journal of the American Chemical Society 41 18020448
2018 Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis. Cell death & disease 39 30310053
2008 Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast. Molecular biology of the cell 38 18199682
2007 The nuclear localization of SOCS6 requires the N-terminal region and negatively regulates Stat3 protein levels. Biochemical and biophysical research communications 38 17603019
2020 Regulation of the miR-19b-mediated SOCS6-JAK2/STAT3 pathway by lncRNA MEG3 is involved in high glucose-induced apoptosis in hRMECs. Bioscience reports 37 32519748
2019 miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC. Cell death & disease 37 30737371
2014 Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6. International journal of oncology 36 24584142
2016 MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1α feedback loop. European review for medical and pharmacological sciences 34 27249600
2015 MiR-142-3p Suppresses SOCS6 Expression and Promotes Cell Proliferation in Nasopharyngeal Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 34 26183850
2021 Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6. Cell death & disease 31 33589592
2006 The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and degradation of SOCS6 associated proteins. FEBS letters 31 16643902
2018 gga-miR-454 suppresses infectious bursal disease virus (IBDV) replication via directly targeting IBDV genomic segment B and cellular Suppressors of Cytokine Signaling 6 (SOCS6). Virus research 30 29777734
2009 SOCS-6 negatively regulates T cell activation through targeting p56lck to proteasomal degradation. The Journal of biological chemistry 30 20007709
2011 SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 22081311
2017 miR-19 promotes osteosarcoma progression by targeting SOCS6. Biochemical and biophysical research communications 27 28986253
2021 MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway. Frontiers in molecular biosciences 25 33937336
2021 Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6. Molecular and cellular biochemistry 25 34100174
2018 SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer. Current cancer drug targets 25 29295692
2017 miR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression. Oncology letters 24 29456720
2008 The Arabidopsis gain-of-function mutant ssi4 requires RAR1 and SGT1b differentially for defense activation and morphological alterations. Molecular plant-microbe interactions : MPMI 24 18052881
2014 SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. International journal of molecular medicine 23 24626642
2023 Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways. Cancer science 21 37972389
2001 Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 21 11337571
2021 Circ_0085289 Alleviates the Progression of Periodontitis by Regulating let-7f-5p/SOCS6 Pathway. Inflammation 20 33710445
2021 SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation. Cancer cell international 20 33712005
2003 Synthesis, resolution, and determination of the absolute configuration of the enantiomers of cis-4,5-dihydroxy-1,2-dithiane 1,1-dioxide, an HIV-1NCp7 inhibitor. Bioorganic & medicinal chemistry 18 12818684
2022 LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis. Inflammation 17 35461393
2017 Cortical Layer Inversion and Deregulation of Reelin Signaling in the Absence of SOCS6 and SOCS7. Cerebral cortex (New York, N.Y. : 1991) 16 26503265
2017 The involvement of suppressor of cytokine signaling 6 (SOCS6) in immune response of Chinese mitten crab Eriocheir sinensis. Fish & shellfish immunology 16 29155031
2018 Interference with NTSR1 Expression Exerts an Anti-Invasion Effect via the Jun/miR-494/SOCS6 Axis of Glioblastoma Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 30261490
2006 Increased SOCS6 stability with PMA requires its N-terminal region and the Erk pathway via Pkcdelta activation. Biochemical and biophysical research communications 14 17210122
2023 Exosome-mediated long noncoding RNA (lncRNA) PART1 suppresses malignant progression of oral squamous cell carcinoma via miR-17-5p/SOCS6 axis. Turkish journal of medical sciences 13 37476905
2022 SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking-Mediated miR-19b. Oxidative medicine and cellular longevity 13 35126805
2017 miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis hematopoietic stem/progenitor cells by targeting SOCS6. Oncotarget 13 28423484
2022 Methyltransferase-like 3 facilitates lung cancer progression by accelerating m6A methylation-mediated primary miR-663 processing and impeding SOCS6 expression. Journal of cancer research and clinical oncology 12 35907010
2021 Circular RNA _0015278 inhibits the progression of non-small cell lung cancer through regulating the microRNA 1278/SOCS6 gene axis. Annals of translational medicine 12 34532392
1983 In vivo effects of cis-5,8,11,14,17-20:5 (n-3) and cis-4,7,10,13,16,19-22:6(n-3) on serum lipoproteins, platelet aggregation, and lipid metabolism in the aorta of rats. The Tohoku journal of experimental medicine 12 6322383
2022 Circ_0062491 alleviates LPS-induced apoptosis and inflammation in periodontitis by regulating miR-498/SOCS6 axis. Innate immunity 11 35678490
2020 microRNA-454 promotes liver tumor-initiating cell expansion by regulating SOCS6. Experimental cell research 11 32165166
2019 kshv-mir-k12-1-5p promotes cell growth and metastasis by targeting SOCS6 in Kaposi's sarcoma cells. Cancer management and research 11 31213914
2022 MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment. Kidney & blood pressure research 10 35038704
2019 Molecular Cloning and Expression Analysis of Three Suppressors of Cytokine Signaling Genes (SOCS5, SOCS6, SOCS7) in the Mealworm Beetle Tenebrio molitor. Insects 10 30884777
2020 cis-4-[18F]fluoro-L-proline Molecular Imaging Experimental Liver Fibrosis. Frontiers in molecular biosciences 9 32500081
2012 Studies on the roles of clathrin-mediated membrane trafficking and zinc transporter Cis4 in the transport of GPI-anchored proteins in fission yeast. PloS one 9 22848669
2023 Protective mechanism of gold nanoparticles on human neural stem cells injured by β-amyloid protein through miR-21-5p/SOCS6 pathway. Neurotoxicology 8 36623431
2022 MIP From Legionella pneumophila Influences the Phagocytosis and Chemotaxis of RAW264.7 Macrophages by Regulating the lncRNA GAS5/miR-21/SOCS6 Axis. Frontiers in cellular and infection microbiology 8 35573783
2020 BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons. International journal of molecular sciences 8 32668737
2022 HnRNPU-AS1 inhibits the proliferation, migration and invasion of HCC cells and induces autophagy through miR-556-3p/ miR-580-3p/SOCS6 axis. Cancer biomarkers : section A of Disease markers 7 35275521
2020 Correction: miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC. Cell death & disease 7 32317628
2017 Expression of SHP-1 and SOCS6 in patients with acute leukemia and their clinical implication. OncoTargets and therapy 7 28408843
2009 Synthesis of trans- and cis-4'-hydroxylomustine and development of validated analytical method for lomustine and trans- and cis-4'-hydroxylomustine in canine plasma. Journal of analytical toxicology 7 20040134
1999 Ab Initio Study of Intramolecular Ring Cyclization of Protonated and BF(3)-Coordinated trans- and cis-4,5-Epoxyhexan-1-ol. The Journal of organic chemistry 6 11674617
2022 Conformational flexibility enables catalysis of phthalate cis-4,5-dihydrodiol dehydrogenase. Archives of biochemistry and biophysics 5 35667443
2021 Inhibition of SOCS6 confers radioresistance in esophageal squamous cell carcinoma. Biochemical and biophysical research communications 5 33689885
2016 A validated, sensitive HPLC-MS/MS method for quantification of cis-para-methyl-4-methylaminorex (cis-4,4'-DMAR) in rat and human plasma: application to pharmacokinetic studies in rats. Drug testing and analysis 5 27509066
2025 MiR-203 improved renal cell injury in diabetic nephropathy by targeting SOCS6/SOCS7 and inhibiting JAK/STAT pathway activation. Scientific reports 4 40155732
2022 Genotoxicological Characterization of (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and Their Association. International journal of molecular sciences 4 35628658
2021 Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice. International journal of molecular sciences 4 34445476
2018 Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment. Molecular imaging and biology 4 29687323
2024 SOCS6, an inhibitory factor in Japanese eel inhibits the type I IFN pathway and the MyD88-mediated NF-kB pathway. Fish & shellfish immunology 2 39276815
2023 Radiosynthesis and Preliminary Evaluation of [11C]SSI-4 for the Positron Emission Tomography Imaging of Stearoyl CoA Desaturase 1. Molecular pharmaceutics 2 37409698
2023 Evaluation of trans- and cis-4-[18F]Fluorogabapentin for Brain PET Imaging. ACS chemical neuroscience 2 37947793
2025 LncRNA CASC2 mediates SOCS6 mRNA stabilization via U2AF2 recruitment to modulate macrophage polarisation in diabetic retinopathy. Diabetic medicine : a journal of the British Diabetic Association 1 40065730
2025 Dual-Mode Radiosensitization of Esophageal Squamous Cell Carcinoma via SOCS6-Loaded Virus-Inspired Manganese-Bismuth Bimetallic Oxide Nanoparticles. Advanced healthcare materials 1 40159874
2025 Suppressor of cytokine signaling 6 (SOCS6) mediates ubiquitination degradation of SLC7A11 to drive ferroptosis and block lipid metabolism in ovarian cancer cells. Gene 1 41061872
2025 [Expression and clinical significance of SIRT1 and SOCS6 in gingival tissue of patients with severe chronic periodontitis]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 1 41311181
2022 Cis-4-[18F]fluoro-L-proline PET/CT molecular imaging quantifying liver collagenogenesis: No existing fibrotic deposition in experimental advanced-stage alcoholic liver fibrosis. Frontiers in nuclear medicine 1 39354960
2026 FTO/SOCS6-m6A axis epigenetic modification links obesity to atopic dermatitis by regulating keratinocyte function. The Journal of investigative dermatology 0 41644088
2026 Excited-state-dependent chiral pathways in the photoisomerization of cis-4,4'-azopyridine. The Journal of chemical physics 0 41919701
2025 Association of SOCS6 Gene Polymorphisms and Promoter Hypermethylation With the Progression of Hepatitis B Virus Infection. International journal of immunogenetics 0 41174995
2023 Serum levels of SOCS6 are decreased in diabetic retinopathy and are related to severity of the disease. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 0 37589228
2023 Quantification Of Collagenogenesis In Experimental Early-stage Alcoholic Liver Fibrosis Using Cis-4-[18F]fluoro-L-Proline microPET. Current medical imaging 0 37622557
2023 Evaluation of trans- and cis-4-[18F]fluorogabapentin for brain PET imaging. bioRxiv : the preprint server for biology 0 37732236