Target Information

Target General Information

Target ID

T92477 (Former ID: TTDR00893)

Target Name

Suppressor of cytokine signaling 3 (SOCS3)

Synonyms

STAT-induced STAT inhibitor 3; STAT induced STAT inhibitor 3; SSI3; SSI-3; SOCS-3; Cytokine-inducible SH2 protein 3; CIS3; CIS-3

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Gene Name

SOCS3

Target Type

Literature-reported target

[1]

Function

SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Probable 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. Seems to recognize IL6ST. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction.

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UniProt ID

SOCS3_HUMAN

Sequence

MVTHSKFPAAGMSRPLDTSLRLKTFSSKSEYQLVVNAVRKLQESGFYWSAVTGGEANLLL
SAEPAGTFLIRDSSDQRHFFTLSVKTQSGTKNLRIQCEGGSFSLQSDPRSTQPVPRFDCV
LKLVHHYMPPPGAPSFPSPPTEPSSEVPEQPSAQPLPGSPPRRAYYIYSGGEKIPLVLSR
PLSSNVATLQHLCRKTVNGHLDSYEKVTQLPGPIREFLDQYDAPL

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3D Structure

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AlphaFold

HIT2.0 ID

T52ARL

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Ubiquitin mediated proteolysis	hsa04120	Affiliated Target
Class: Genetic Information Processing => Folding, sorting and degradation	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
TNF signaling pathway	hsa04668	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Insulin signaling pathway	hsa04910	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Prolactin signaling pathway	hsa04917	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Adipocytokine signaling pathway	hsa04920	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Growth hormone synthesis, secretion and action	hsa04935	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
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Degree	22	Degree centrality	2.36E-03	Betweenness centrality	2.95E-04
Closeness centrality	2.40E-01	Radiality	1.42E+01	Clustering coefficient	2.94E-01
Neighborhood connectivity	4.64E+01	Topological coefficient	9.59E-02	Eccentricity	12
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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003 Aug;9(8):1047-54.

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