SOCS2

SOCS2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2C9W, 4JGH, 5BO4
Identifiers
Aliases	SOCS2, CIS2, Cish2, SOCS-2, SSI-2, SSI2, STATI2, suppressor of cytokine signaling 2
External IDs	OMIM: 605117 MGI: 1201787 HomoloGene: 2880 GeneCards: SOCS2
Gene location (Human)
Chr.	Chromosome 12 (human)[1]
End	93,583,487 bp[1]
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)[2]
End	95,253,042 bp[2]
RNA expression pattern
	Top expressed in
	secondary oocyte; ; canal of the cervix; ; vena cava; ; myometrium; ; seminal vesicula; ; prostate; ; pituitary gland; ; left uterine tube; ; anterior pituitary; ; mucosa of urinary bladder;
	Top expressed in
	cumulus cell; ; olfactory epithelium; ; left lung lobe; ; stria vascularis; ; right lung; ; interventricular septum; ; right lung lobe; ; superior surface of tongue; ; myocardium of ventricle; ; parotid gland;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	insulin-like growth factor receptor binding; protein kinase inhibitor activity; JAK pathway signal transduction adaptor activity; protein binding; growth hormone receptor binding; 1-phosphatidylinositol-3-kinase regulator activity;
Cellular component	cytoplasm; cytosol; phosphatidylinositol 3-kinase complex;
Biological process	receptor signaling pathway via JAK-STAT; response to estradiol; intracellular signal transduction; negative regulation of protein kinase activity; cytokine-mediated signaling pathway; negative regulation of apoptotic process; negative regulation of insulin receptor signaling pathway; cellular response to hormone stimulus; growth hormone receptor signaling pathway; regulation of signal transduction; regulation of cell growth; protein ubiquitination; regulation of growth; negative regulation of signal transduction; negative regulation of receptor signaling pathway via JAK-STAT; positive regulation of signal transduction; lactation; regulation of multicellular organism growth; negative regulation of multicellular organism growth; post-translational protein modification; positive regulation of neuron differentiation; mammary gland alveolus development; interleukin-7-mediated signaling pathway; regulation of phosphatidylinositol 3-kinase activity; phosphatidylinositol phosphate biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	8835
	216233
	ENSG00000120833
	ENSMUSG00000020027
	O14508
	O35717
NM_001270467; NM_001270468; NM_001270469; NM_001270470; NM_001270471;
	NM_003877
	NM_001168655; NM_001168656; NM_001168657; NM_007706
NP_001257396; NP_001257397; NP_001257398; NP_001257399; NP_001257400;
	NP_003868
	NP_001162126; NP_001162127; NP_001162128; NP_031732
	Wikidata
View/Edit Human	View/Edit Mouse

Suppressor of cytokine signaling 2 is a protein that in humans is encoded by the SOCS2 gene.[5][6][7]

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10 and interferon-gamma (IFN-gamma). The protein encoded by this gene is found to interact with the cytoplasmic domain of insulin-like growth factor 1 receptor (IGF1R), and thus is thought to be involved in the regulation of IGF1R mediated cell signaling.[8] Knockout studies in mice also suggested a regulatory role of this gene in IGF-1 related growth control.[7][9]

Interactions

SOCS2 has been shown to interact with insulin-like growth factor 1 receptor[8] and erythropoietin receptor.[10] Additionally, it acts as a substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex.[11] It is under investigation for use in targeted protein degradation.[12]

References

GRCh38: Ensembl release 89: ENSG00000120833 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000020027 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, et al. (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–446. doi:10.1006/bbrc.1997.7484. PMID 9344848.
Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, et al. (August 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochemical and Biophysical Research Communications. 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833.
"Entrez Gene: SOCS2 suppressor of cytokine signaling 2".
Dey BR, Spence SL, Nissley P, Furlanetto RW (September 1998). "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor". The Journal of Biological Chemistry. 273 (37): 24095–24101. doi:10.1074/jbc.273.37.24095. PMID 9727029.
Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, et al. (June 2002). "Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b)". Molecular Endocrinology. 16 (6): 1394–1406. doi:10.1210/mend.16.6.0845. PMID 12040024.
Eyckerman S, Verhee A, der Heyden JV, Lemmens I, Ostade XV, Vandekerckhove J, Tavernier J (December 2001). "Design and application of a cytokine-receptor-based interaction trap". Nature Cell Biology. 3 (12): 1114–1119. doi:10.1038/ncb1201-1114. PMID 11781573. S2CID 10228882.
Kung WW, Ramachandran S, Makukhin N, Bruno E, Ciulli A (June 2019). "Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase". Nature Communications. 10 (1): 2534. Bibcode:2019NatCo..10.2534K. doi:10.1038/s41467-019-10190-4. PMC 6557900. PMID 31182716.
Ramachandran S, Makukhin N, Haubrich K, Nagala M, Forrester B, Lynch D, et al. (2022-10-18). "Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2". Nature Communications. 14: 6345. doi:10.1038/s41467-023-41894-3.

External links

SOCS2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000120833 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020027 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9344848-5] Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, et al. (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–446. doi:10.1006/bbrc.1997.7484. PMID 9344848.

[pmid9266833-6] Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, et al. (August 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochemical and Biophysical Research Communications. 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833.

[entrez_8835-7] "Entrez Gene: SOCS2 suppressor of cytokine signaling 2".

[pmid9727029-8] Dey BR, Spence SL, Nissley P, Furlanetto RW (September 1998). "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor". The Journal of Biological Chemistry. 273 (37): 24095–24101. doi:10.1074/jbc.273.37.24095. PMID 9727029.

[pmid12040024-9] Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, et al. (June 2002). "Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b)". Molecular Endocrinology. 16 (6): 1394–1406. doi:10.1210/mend.16.6.0845. PMID 12040024.

[pmid11781573-10] Eyckerman S, Verhee A, der Heyden JV, Lemmens I, Ostade XV, Vandekerckhove J, Tavernier J (December 2001). "Design and application of a cytokine-receptor-based interaction trap". Nature Cell Biology. 3 (12): 1114–1119. doi:10.1038/ncb1201-1114. PMID 11781573. S2CID 10228882.

[11] Kung WW, Ramachandran S, Makukhin N, Bruno E, Ciulli A (June 2019). "Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase". Nature Communications. 10 (1): 2534. Bibcode:2019NatCo..10.2534K. doi:10.1038/s41467-019-10190-4. PMC 6557900. PMID 31182716.

[12] Ramachandran S, Makukhin N, Haubrich K, Nagala M, Forrester B, Lynch D, et al. (2022-10-18). "Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2". Nature Communications. 14: 6345. doi:10.1038/s41467-023-41894-3.

SOCS2

Interactions

References

Further reading

External links