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; OMA:SOCS2 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q22 Start 93,569,814 bp[1] End 93,583,487 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C2|10 49.35 cM Start 95,221,224 bp[2] End 95,253,042 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte canal of the cervix vena cava body of uterus myometrium seminal vesicula Epithelium of choroid plexus ectocervix prostate Pituitary Gland Top expressed in cumulus cell Ileal epithelium olfactory epithelium vestibular membrane of cochlear duct left lung lobe vestibular sensory epithelium stria vascularis Gonadal ridge right lung interventricular septum More reference expression data BioGPS 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 Species Human Mouse Entrez 8835 216233 Ensembl ENSG00000120833 ENSMUSG00000020027 UniProt O14508 O35717 RefSeq (mRNA) NM_001270467 NM_001270468 NM_001270469 NM_001270470 NM_001270471 NM_003877 NM_001168655 NM_001168656 NM_001168657 NM_007706 RefSeq (protein) NP_001257396 NP_001257397 NP_001257398 NP_001257399 NP_001257400 NP_003868 NP_001162126 NP_001162127 NP_001162128 NP_031732 Location (UCSC) Chr 12: 93.57 – 93.58 Mb Chr 10: 95.22 – 95.25 Mb PubMed search [3] [4]
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

1. GRCh38: Ensembl release 89: ENSG00000120833 – Ensembl, May 2017
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.
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.
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.
7. "Entrez Gene: SOCS2 suppressor of cytokine signaling 2".
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.
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.
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 (1): 6345. doi:10.1038/s41467-023-41894-3. PMC 10564737. PMID 37816714.

Further reading

• Lopaczynski W (1999). "Differential regulation of signaling pathways for insulin and insulin-like growth factor I". Acta Biochimica Polonica. 46 (1): 51–60. doi:10.18388/abp.1999_4183. PMID 10453981.
• Wang J, Campbell IL (February 2002). "Cytokine signaling in the brain: putting a SOCS in it?". Journal of Neuroscience Research. 67 (4): 423–427. doi:10.1002/jnr.10145. PMID 11835308. S2CID 33269663.
• Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ (May 2002). "The SOCS box: a tale of destruction and degradation". Trends in Biochemical Sciences. 27 (5): 235–241. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535.
• Pezet A, Buteau H, Kelly PA, Edery M (May 1997). "The last proline of Box 1 is essential for association with JAK2 and functional activation of the prolactin receptor". Molecular and Cellular Endocrinology. 129 (2): 199–208. doi:10.1016/S0303-7207(97)00063-4. PMID 9202403. S2CID 10606236.
• 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.
• Pezet A, Favre H, Kelly PA, Edery M (August 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". The Journal of Biological Chemistry. 274 (35): 24497–24502. doi:10.1074/jbc.274.35.24497. PMID 10455112.
• Yandava CN, Pillari A, Drazen JM (October 1999). "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively". Genomics. 61 (1): 108–111. doi:10.1006/geno.1999.5937. PMID 10512686.
• Ram PA, Waxman DJ (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". The Journal of Biological Chemistry. 274 (50): 35553–35561. doi:10.1074/jbc.274.50.35553. PMID 10585430.
• Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, et al. (June 2000). "Gigantism in mice lacking suppressor of cytokine signalling-2". Nature. 405 (6790): 1069–1073. Bibcode:2000Natur.405.1069M. doi:10.1038/35016611. PMID 10890450. S2CID 13750159.
• Shen X, Hong F, Nguyen VA, Gao B (September 2000). "IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3". FEBS Letters. 480 (2–3): 132–136. doi:10.1016/S0014-5793(00)01905-0. PMID 11034314. S2CID 84290049.
• 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.
• Schultheis B, Carapeti-Marootian M, Hochhaus A, Weisser A, Goldman JM, Melo JV (March 2002). "Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism". Blood. 99 (5): 1766–1775. doi:10.1182/blood.V99.5.1766. PMID 11861294.
• Blumenstein M, Bowen-Shauver JM, Keelan JA, Mitchell MD (March 2002). "Identification of suppressors of cytokine signaling (SOCS) proteins in human gestational tissues: differential regulation is associated with the onset of labor". The Journal of Clinical Endocrinology and Metabolism. 87 (3): 1094–1097. doi:10.1210/jcem.87.3.8463. PMID 11889171.
• Biener E, Maurice S, Sandowski Y, Cohen Y, Gusakowsky EE, Hooghe R, et al. (July 2002). "Recombinant human CIS2 (SOCS2) protein: subcloning, expression, purification, and characterization". Protein Expression and Purification. 25 (2): 305–312. doi:10.1016/S1046-5928(02)00013-X. PMID 12135564.

External links

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