SOCS4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0019221 cytokine-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: SOCS4 is induced by cytokines and acts as a negative feedback regulator in cytokine signaling pathways. While SOCS4 is part of the SOCS family which regulates cytokine signaling, its primary characterized function is EGFR regulation rather than direct JAK/STAT inhibition like SOCS1/3. The deep research shows SOCS4 can modulate cytokine responses indirectly through EGFR/STAT3 cross-talk and is critical for preventing cytokine storms during infection. Reason: SOCS4 clearly functions in cytokine-mediated signaling pathways as demonstrated by influenza infection studies showing SOCS4-KO mice have exaggerated cytokine storm and dysregulated chemokine production. IBA phylogenetic inference is well-supported by experimental data showing SOCS4 is induced by cytokines and regulates inflammatory responses. This is a core biological process for SOCS4. Supporting Evidence: file:human/SOCS4/SOCS4-deep-research-falcon.md Mice lacking the Socs4 gene were found to be highly susceptible to influenza, suffering more severe disease compared to wild-type mice. SOCS4-knockout mice infected with H1N1 influenza showed an exaggerated inflammatory response in the lungs – often termed a 'cytokine storm' – characterized by excessive production of pro-inflammatory chemokines and cytokines that led to tissue damage. file:human/SOCS4/SOCS4-deep-research-openai.md See deep research file for comprehensive analysis
GO:0009968 negative regulation of signal transduction	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: This term is too broad and uninformative. SOCS4 does negatively regulate signal transduction, but this annotation provides no specificity about which pathways or mechanisms. More specific terms like GO:0007175 (negative regulation of EGFR activity) or GO:0032436 (positive regulation of proteasomal degradation) better capture SOCS4's actual molecular function. Reason: While biologically true, this broad regulation term is less useful than the already reviewed specific annotations for SOCS4: negative regulation of EGFR activity, positive regulation of proteasomal ubiquitin-dependent protein catabolism, protein ubiquitination, and ubiquitin-like ligase-substrate adaptor activity. Keeping the broad term as a replacement target would obscure rather than clarify the mechanism.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA GO_REF:0000002	ACCEPT	Summary: SOCS4 functions as an E3 ubiquitin ligase adaptor. Its SOCS box domain recruits the Elongin B/C-Cullin-5 ubiquitin ligase complex to targets bound by its SH2 domain (particularly phosphorylated EGFR), promoting their polyubiquitination and proteasomal degradation. This is well-established by structural studies and functional experiments. Reason: This annotation accurately captures SOCS4's core molecular mechanism. The crystal structure of SOCS4-Elongin B/C complex (PMID:17997974) demonstrates how SOCS box recruits ubiquitination machinery. Deep research confirms SOCS4 promotes EGFR degradation through this mechanism. This is a fundamental aspect of SOCS4 function and merits acceptance despite IEA evidence code. Supporting Evidence: file:human/SOCS4/SOCS4-deep-research-falcon.md Once bound, the C-terminal SOCS box recruits an E3 ubiquitin ligase complex: the SOCS box interacts with the adaptor proteins Elongin B and Elongin C, which in turn couple SOCS4 to a Cullin-5/RING ubiquitin ligase scaffold. This SOCS4–Elongin-Cullin complex catalyzes the polyubiquitination of the associated target protein, marking it for proteasomal degradation. file:human/SOCS4/SOCS4-uniprot.txt Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: This term is extremely broad and uninformative. While SOCS4 does participate in intracellular signal transduction by modulating receptor signaling, this high-level process term provides minimal functional information. More specific child terms already annotated (cytokine signaling, EGFR regulation) are far more informative. Reason: This annotation is at the wrong level of granularity. SOCS4's role is specifically as a SOCS-box adaptor that attenuates activated EGFR and related cytokine/growth-factor signaling through receptor binding and ubiquitin-dependent degradation. The existing reviewed annotations already capture that biology without adding the unsupported ERBB2-specific pathway.
GO:0005515 protein binding	IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo...	MODIFY	Summary: This annotation documents protein-protein interaction with FRS3 (O43559) from a phosphotyrosine-dependent interaction screen. While this is experimental evidence for protein binding, the term "protein binding" alone is uninformative and should be avoided per curation guidelines. Reason: Per curation guidelines: "Avoid the term protein binding, this doesn't tell us anything about the actual function." While PMID:25814554 provides experimental evidence for SOCS4 binding to FRS3, the annotation should use more specific molecular function terms. SOCS4's SH2 domain binds phosphotyrosine residues, so "phosphotyrosine residue binding" (GO:0001784) or "SH2 domain binding" (GO:0042169) would be more informative. Proposed replacements: phosphotyrosine residue binding SH2 domain binding Supporting Evidence: PMID:25814554 We extended an established yeast two-hybrid system employing human protein kinases for the analyses of phospho-tyrosine (pY)-dependent PPIs in a direct experimental, large-scale approach. We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells.
GO:0005515 protein binding	IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo...	MODIFY	Summary: This annotation documents protein-protein interaction with GRB2 (P62993) from PMID:25814554. This is a duplicate GO term (same PMID, different interacting partner). While experimentally validated, "protein binding" is too vague per curation guidelines. Reason: Same issue as previous protein binding annotation. SOCS4's interaction with GRB2 (an SH2/SH3 adaptor protein) likely involves phosphotyrosine-mediated binding through SOCS4's SH2 domain. Should use more specific molecular function terms that describe the binding mechanism rather than generic "protein binding". Proposed replacements: phosphotyrosine residue binding SH2 domain binding Supporting Evidence: PMID:25814554 In order to systematically screen for pY-dependent PPIs, we paired bait proteins containing phospho-tyrosine-recognition domains (pY readers, Lim & Pawson, 2010) with non-receptor tyrosine kinases and tested a human proteome-scale prey matrix containing ∽17,000 ORFs for interaction.
GO:0005515 protein binding	IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo...	MODIFY	Summary: This annotation documents protein-protein interaction with PIK3R3 (Q92569) from PMID:25814554. Third duplicate of generic protein binding term from same phosphotyrosine interaction screen. Reason: Same rationale as above - "protein binding" is too uninformative. PIK3R3 is the p55gamma regulatory subunit of PI3K, which also contains SH2 domains. SOCS4's interaction likely involves phosphotyrosine recognition. More specific molecular function terms should be used. Proposed replacements: phosphotyrosine residue binding SH2 domain binding Supporting Evidence: PMID:25814554 We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells.
GO:0005515 protein binding	IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo...	MODIFY	Summary: This annotation documents interaction with RBP7 (Q96R05) from PMID:25814554. Fourth instance of generic protein binding from same study. Reason: Continuing pattern - all these PMID:25814554 annotations should be consolidated under more specific molecular function terms like phosphotyrosine binding rather than multiple redundant "protein binding" entries. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:25814554 In summary, we report a large data resource comprising 336 independent and 292 phosphorylation-dependent protein-protein interactions, the latter involving 52 SH2-containing, 19 PTB domain-containing proteins
GO:0005515 protein binding	IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo...	MODIFY	Summary: This annotation documents interaction with PINK1 (Q9BXM7) from PMID:25814554. Fifth instance from same phosphotyrosine interaction screen. Reason: Same issue - multiple redundant "protein binding" annotations from a single high-throughput screen should be replaced with one or more specific molecular function terms that describe SOCS4's actual binding mechanism (SH2-mediated phosphotyrosine recognition). Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:25814554 The validation rate of ∽50% (Fig3A) is similar for phospho-tyrosine-dependent and phospho-tyrosine-independent interactions.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: This annotation documents interaction with TEKT4 (Q8WW24) from PMID:32296183 (binary protein interactome reference map). TEKT4 is a testis-specific tektin involved in sperm flagella. This interaction seems unlikely to be functionally relevant to SOCS4's core role in receptor tyrosine kinase regulation. Reason: High-throughput binary interaction data from PMID:32296183 often includes false positives or non-physiological interactions. TEKT4 is testis-specific cytoskeletal protein with no obvious functional connection to SOCS4's role in EGFR/cytokine signaling. Even if interaction is real, generic "protein binding" annotation is uninformative. Should use specific molecular function term if mechanism is known, or mark as non-core interaction. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32296183 The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: This annotation documents interaction with DMWD (G5E9A7) from PMID:32814053 (neurodegenerative disease interactome study). DMWD is involved in myotonic dystrophy. Unclear functional relevance to SOCS4. Reason: Another high-throughput study (neurodegenerative disease proteins) with questionable functional relevance. Generic "protein binding" provides no useful functional information. Should be replaced with specific molecular function term or marked as peripheral/non-core. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with BSCL2 (J3KQ12) from neurodegenerative disease interactome. BSCL2/seipin is involved in lipid droplet formation. Reason: Same issues - high-throughput data, unclear functional relevance, uninformative generic term. Should use specific molecular function terms. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with SPTLC1 isoform (O15269-2) from PMID:32814053. SPTLC1 is serine palmitoyltransferase involved in sphingolipid biosynthesis. Reason: Neurodegenerative disease interactome data with no clear connection to SOCS4's known functions. Generic term uninformative. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with HTRA2 (O43464) from PMID:32814053. HTRA2 is a mitochondrial serine protease involved in apoptosis. Reason: High-throughput neurodegenerative disease study. Unclear functional relevance. Generic term uninformative. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with GARS1 (P41250) from PMID:32814053. GARS1 is glycyl-tRNA synthetase. Reason: High-throughput study with no functional context. Generic "protein binding" uninformative. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with HTT/huntingtin (P42858) from neurodegenerative disease interactome. HTT is the protein mutated in Huntington's disease. Reason: From neurodegenerative disease focused screen. While potentially interesting, generic "protein binding" term is uninformative and should be replaced with specific molecular function. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with SPRED1 (Q7Z699) from PMID:32814053. SPRED1 is a negative regulator of MAPK/ERK signaling. This interaction is more plausible functionally since both proteins negatively regulate RTK signaling. Reason: While this interaction with SPRED1 has better functional plausibility (both are RTK signaling inhibitors), the generic "protein binding" term remains uninformative. Should use specific molecular function term. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with JPH3 (Q8WXH2) from PMID:32814053. JPH3/junctophilin-3 is involved in junctional membrane complexes, implicated in Huntington's disease-like 2. Reason: Neurodegenerative disease interactome with unclear functional connection to SOCS4 biology. Generic term uninformative. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MODIFY	Summary: Interaction with PANK2 isoform (Q9BZ23-2) from PMID:32814053. PANK2 is pantothenate kinase involved in CoA biosynthesis. Reason: High-throughput neurodegenerative disease study. No clear functional connection. Generic term uninformative. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:32814053 Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions.
GO:0016567 protein ubiquitination	IEA GO_REF:0000041	ACCEPT	Summary: SOCS4 promotes protein ubiquitination by serving as an adaptor that recruits E3 ubiquitin ligase machinery (Elongin B/C-Cullin-5) to bound substrates like activated EGFR. This is a core aspect of SOCS4's mechanism of action. Reason: While this is IEA (inferred from UniPathway), it accurately represents SOCS4's established molecular function. The SOCS box domain recruits ubiquitin ligase complexes to promote degradation of receptor targets. This is well-supported by structural and functional studies showing SOCS4-mediated EGFR ubiquitination and degradation. Core mechanism annotation that should be retained. Supporting Evidence: file:human/SOCS4/SOCS4-deep-research-falcon.md The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. This SOCS4–Elongin-Cullin complex catalyzes the polyubiquitination of the associated target protein, marking it for proteasomal degradation. file:human/SOCS4/SOCS4-uniprot.txt PATHWAY: Protein modification; protein ubiquitination.
GO:0007175 negative regulation of epidermal growth factor-activated receptor activity	IDA PMID:15590694 Suppressors of cytokine signaling 4 and 5 regulate epidermal...	ACCEPT	Summary: This is the primary, best-characterized function of SOCS4. PMID:15590694 experimentally demonstrates that SOCS4 and SOCS5 negatively regulate EGFR signaling. SOCS4's SH2 domain binds phospho-Y1092 on activated EGFR, recruiting ubiquitin ligase machinery for receptor degradation while simultaneously blocking STAT3 binding to that site. Reason: This is the gold-standard annotation for SOCS4 - experimental IDA evidence from the seminal paper characterizing SOCS4/5 function in EGFR regulation. Deep research confirms EGFR is the primary characterized target of SOCS4. UniProt function section emphasizes EGFR degradation. This represents SOCS4's core molecular function and should be retained as a cornerstone annotation. Well-supported by structural studies (PMID:17997974) and functional validation. Supporting Evidence: PMID:15590694 The expression of SOCS5 led to a marked reduction in EGFR expression levels by promoting EGFR degradation. file:human/SOCS4/SOCS4-deep-research-falcon.md A defining target of SOCS4 is the Epidermal Growth Factor Receptor (EGFR), a receptor tyrosine kinase. SOCS4 was shown to bind directly to a particular phosphotyrosine site on the activated EGFR (tyrosine 1092 in the human EGFR cytoplasmic domain) via its SH2 domain.
GO:1990756 ubiquitin-like ligase-substrate adaptor activity	IDA PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct...	NEW	Summary: SOCS4 is a substrate-recognition adaptor for a CRL5-type E3 ubiquitin ligase complex. Its SH2 domain binds phosphorylated substrates such as EGFR, while its SOCS box recruits Elongin B/C-Cullin ligase machinery. Reason: This MF term captures the molecular boundary more precisely than treating SOCS4 as a ubiquitin-transfer enzyme. SOCS4 directly bridges substrate recognition and ligase recruitment, so GO:1990756 should accompany the accepted protein ubiquitination process annotation. Supporting Evidence: PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. file:human/SOCS4/SOCS4-uniprot.txt Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
GO:0005737 cytoplasm	TAS PMID:15590694 Suppressors of cytokine signaling 4 and 5 regulate epidermal...	NEW	Summary: SOCS4 is a cytosolic SOCS-box adaptor that is recruited to activated receptor complexes through phosphotyrosine-dependent binding. Reason: Cytoplasm is the appropriate cellular context for a soluble SOCS family adaptor that binds phosphorylated receptor tails and recruits Elongin B/C-Cullin ligase machinery. This is supported by the EGFR degradation literature and UniProt functional description, rather than being a bookkeeping addition to match core_functions. Supporting Evidence: PMID:15590694 Here we show that the expression of SOCS5 and its closest homolog SOCS4 is elevated in cells following treatment with EGF, similar to several negative feedback regulators of EGFR whose expression is up-regulated upon receptor activation. PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. file:human/SOCS4/SOCS4-deep-research-falcon.md SOCS4's SH2 domain recognizes specific phosphotyrosine motifs on activated EGFR (Y1092), while SOCS box recruits Elongin B/C-Cullin-5 ubiquitin ligase complex, catalyzing polyubiquitination and proteasomal degradation of EGFR. This dual mechanism both blocks STAT3 binding and promotes receptor turnover file:human/SOCS4/SOCS4-uniprot.txt Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR
GO:0005886 plasma membrane	TAS PMID:15590694 Suppressors of cytokine signaling 4 and 5 regulate epidermal...	NEW	Summary: SOCS4 acts on activated EGFR, a plasma-membrane receptor tyrosine kinase, through phosphotyrosine-dependent recruitment to receptor signaling complexes. Reason: Plasma membrane is a receptor-complex context for SOCS4 function rather than evidence that SOCS4 is an integral membrane protein. The term is justified by the experimentally characterized role in activated EGFR regulation and should be interpreted as receptor-associated localization for this adaptor. Supporting Evidence: PMID:15590694 Here we show that the expression of SOCS5 and its closest homolog SOCS4 is elevated in cells following treatment with EGF, similar to several negative feedback regulators of EGFR whose expression is up-regulated upon receptor activation. PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. file:human/SOCS4/SOCS4-deep-research-falcon.md SOCS4's SH2 domain recognizes specific phosphotyrosine motifs on activated EGFR (Y1092), while SOCS box recruits Elongin B/C-Cullin-5 ubiquitin ligase complex, catalyzing polyubiquitination and proteasomal degradation of EGFR. This dual mechanism both blocks STAT3 binding and promotes receptor turnover file:human/SOCS4/SOCS4-uniprot.txt Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR
GO:0031466 Cul5-RING ubiquitin ligase complex	TAS PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct...	NEW	Summary: SOCS4 functions as the substrate-recognition component of an Elongin B/C-Cullin-5 SOCS-box E3 ligase complex. Reason: The SOCS box recruits Elongin B/C and Cullin-5 ubiquitin ligase machinery, while the SH2 domain provides substrate recognition. PMID:17997974 directly supports SOCS4-Elongin B/C complex formation, and the UniProt functional statement supports the ECS/CRL5 complex context. Supporting Evidence: PMID:15590694 Here we show that the expression of SOCS5 and its closest homolog SOCS4 is elevated in cells following treatment with EGF, similar to several negative feedback regulators of EGFR whose expression is up-regulated upon receptor activation. PMID:17997974 Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. file:human/SOCS4/SOCS4-deep-research-falcon.md SOCS4's SH2 domain recognizes specific phosphotyrosine motifs on activated EGFR (Y1092), while SOCS box recruits Elongin B/C-Cullin-5 ubiquitin ligase complex, catalyzing polyubiquitination and proteasomal degradation of EGFR. This dual mechanism both blocks STAT3 binding and promotes receptor turnover file:human/SOCS4/SOCS4-uniprot.txt Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR

Gene Description

Existing Annotations Review

Core Functions

Phosphotyrosine-dependent ubiquitin ligase-substrate adaptor activity targeting activated EGFR for proteasomal degradation

References

Deep Research

Cyberian

Falcon

OpenAI

📚 Additional Documentation

Notes

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