Suppressor of cytokine signaling 1

SOCS1
Identifiers
Aliases	SOCS1, CIS1, CISH1, JAB, SOCS-1, SSI-1, SSI1, TIP3, suppressor of cytokine signaling 1, TIP-3, AISIMD
External IDs	OMIM: 603597; MGI: 1354910; HomoloGene: 2776; GeneCards: SOCS1; OMA:SOCS1 - orthologs
Gene location (Human)
Chr.	Chromosome 16 (human)
End	11,256,204 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	10,603,400 bp
RNA expression pattern
	Top expressed in
	beta cell; ; sperm; ; canal of the cervix; ; testicle; ; spleen; ; appendix; ; superficial temporal artery; ; granulocyte; ; lymph node; ; ectocervix;
	Top expressed in
	thymus; ; granulocyte; ; submandibular gland; ; mesenteric lymph nodes; ; zygote; ; embryo; ; morula; ; secondary oocyte; ; bone marrow; ; vastus lateralis muscle;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	insulin-like growth factor receptor binding; protein kinase inhibitor activity; protein binding; protein kinase binding; kinase inhibitor activity; 1-phosphatidylinositol-3-kinase regulator activity;
Cellular component	cytoplasm; cytosol; cytoplasmic vesicle; nucleus; nucleoplasm; cytoplasmic ribonucleoprotein granule; phosphatidylinositol 3-kinase complex;
Biological process	intracellular signal transduction; regulation of interferon-gamma-mediated signaling pathway; protein ubiquitination; regulation of growth; negative regulation of signal transduction; negative regulation of protein kinase activity; negative regulation of receptor signaling pathway via JAK-STAT; positive regulation of regulatory T cell differentiation; interleukin-7-mediated signaling pathway; regulation of protein phosphorylation; cytokine-mediated signaling pathway; negative regulation of tyrosine phosphorylation of STAT protein; positive regulation of CD4-positive, alpha-beta T cell differentiation; negative regulation of CD8-positive, alpha-beta T cell differentiation; negative regulation of insulin receptor signaling pathway; receptor signaling pathway via JAK-STAT; regulation of activation of Janus kinase activity; negative regulation of kinase activity; regulation of tyrosine phosphorylation of STAT protein; regulation of phosphatidylinositol 3-kinase activity; fat cell differentiation; regulation of receptor signaling pathway via JAK-STAT; phosphatidylinositol phosphate biosynthetic process; cellular response to amino acid stimulus;
	Sources:Amigo / QuickGO
Orthologs
	8651
	12703
	ENSG00000185338
	ENSMUSG00000038037
	O15524
	O35716
	NM_003745
	NM_001271603; NM_009896
	NP_003736
	NP_001258532; NP_034026
	Wikidata
View/Edit Human	View/Edit Mouse

Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene.^[5]^[6] SOCS1 orthologs^[7] have been identified in several mammals for which complete genome data are available.

Function

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 IL2, IL3 erythropoietin (EPO), GM-CSF, and interferon-gamma (IFN-γ). The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-γ action, which is required for normal postnatal growth and survival.^[8]

Several recent viral studies have shown that viral genes, such as Tax gene product (Tax), encoded by HTLV-1, could hijack SOCS1 to inhibit host antiviral pathways, as a strategy to evade host immunity.^[9]

Interactions

The suppressor of cytokine signaling 1 has been shown to interact with:

Tax,^[9]
CD117,^[10]
Colony stimulating factor 1 receptor^[11]
Growth hormone receptor,^[12]
IRS2,^[13]
Janus kinase 2,^[14]^[15]^[16]^[17]^[18]^[19] and
TEC.^[20]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000185338 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038037 – 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.
^ Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (June 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". The EMBO Journal. 14 (12): 2816–26. doi:10.1002/j.1460-2075.1995.tb07281.x. PMC 398400. PMID 7796808.
^ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (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.
^ "OrthoMaM phylogenetic marker: SOCS1 coding sequence".
^ "Entrez Gene: SOCS1 suppressor of cytokine signaling 1".
^ ^a ^b Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW (July 2011). "Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1". Journal of Virology. 85 (14): 6955–62. doi:10.1128/JVI.00007-11. PMC 3126571. PMID 21593151.
^ De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.
^ Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". The Journal of Biological Chemistry. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560.
^ 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): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430.
^ Rui L, Yuan M, Frantz D, Shoelson S, White MF (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". The Journal of Biological Chemistry. 277 (44): 42394–8. doi:10.1074/jbc.C200444200. PMID 12228220.
^ Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.
^ Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (December 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology. 142 (12): 5286–93. doi:10.1210/endo.142.12.8549. PMID 11713228.
^ Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature. 387 (6636): 921–4. Bibcode:1997Natur.387..921E. doi:10.1038/43213. PMID 9202126. S2CID 4347361.
^ 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): 24497–502. doi:10.1074/jbc.274.35.24497. PMID 10455112.
^ Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Molecular and Cellular Biology. 22 (10): 3316–26. doi:10.1128/mcb.22.10.3316-3326.2002. PMC 133778. PMID 11971965.
^ Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.
^ Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (October 1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". The Journal of Biological Chemistry. 272 (43): 27178–82. doi:10.1074/jbc.272.43.27178. PMID 9341160.

Krebs DL, Hilton DJ (2001). "SOCS proteins: negative regulators of cytokine signaling". Stem Cells. 19 (5): 378–87. doi:10.1634/stemcells.19-5-378. PMID 11553846.
Wang J, Campbell IL (February 2002). "Cytokine signaling in the brain: putting a SOCS in it?". Journal of Neuroscience Research. 67 (4): 423–7. 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): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535.
Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ (June 1997). "A family of cytokine-inducible inhibitors of signalling". Nature. 387 (6636): 917–21. Bibcode:1997Natur.387..917S. doi:10.1038/43206. PMID 9202125. S2CID 4325620.
Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature. 387 (6636): 921–4. Bibcode:1997Natur.387..921E. doi:10.1038/43213. PMID 9202126. S2CID 4347361.
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): 24095–101. doi:10.1074/jbc.273.37.24095. PMID 9727029.
De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.
Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BT, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (March 1999). "The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation". Proceedings of the National Academy of Sciences of the United States of America. 96 (5): 2071–6. Bibcode:1999PNAS...96.2071Z. doi:10.1073/pnas.96.5.2071. PMC 26738. PMID 10051596.
Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.
Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN (September 1999). "SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality". Cell. 98 (5): 609–16. doi:10.1016/S0092-8674(00)80048-3. PMID 10490100. S2CID 14654250.
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): 108–11. doi:10.1006/geno.1999.5937. PMID 10512686.
Okabe S, Tauchi T, Morita H, Ohashi H, Yoshimura A, Ohyashiki K (October 1999). "Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway". Experimental Hematology. 27 (10): 1542–7. doi:10.1016/S0301-472X(99)00094-6. PMID 10517496.
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): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430.
Sporri B, Kovanen PE, Sasaki A, Yoshimura A, Leonard WJ (January 2001). "JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling". Blood. 97 (1): 221–6. doi:10.1182/blood.V97.1.221. PMID 11133764.
Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (January 2001). "Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation". The Journal of Experimental Medicine. 193 (2): 263–9. doi:10.1084/jem.193.2.263. PMC 2193341. PMID 11208867.
Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". The Journal of Biological Chemistry. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560.
Mooney RA, Senn J, Cameron S, Inamdar N, Boivin LM, Shang Y, Furlanetto RW (July 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. 276 (28): 25889–93. doi:10.1074/jbc.M010579200. PMID 11342531.
Bellezza I, Neuwirt H, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A, Doppler W, Culig Z (December 2006). "Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer". The American Journal of Pathology. 169 (6): 2199–208. doi:10.2353/ajpath.2006.060171. PMC 1762483. PMID 17148681.
Neuwirt H, Puhr M, Santer FR, Susani M, Doppler W, Marcias G, Rauch V, Brugger M, Hobisch A, Kenner L, Culig Z (May 2009). "Suppressor of cytokine signaling (SOCS)-1 is expressed in human prostate cancer and exerts growth-inhibitory function through down-regulation of cyclins and cyclin-dependent kinases". The American Journal of Pathology. 174 (5): 1921–30. doi:10.2353/ajpath.2009.080751. PMC 2671279. PMID 19342366.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185338 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000038037 – 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.

[pmid7796808-5] Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (June 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". The EMBO Journal. 14 (12): 2816–26. doi:10.1002/j.1460-2075.1995.tb07281.x. PMC 398400. PMID 7796808.

[pmid9266833-6] Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (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.

[OrthoMaM-7] "OrthoMaM phylogenetic marker: SOCS1 coding sequence".

[entrez-8] "Entrez Gene: SOCS1 suppressor of cytokine signaling 1".

[pmid21593151-9] Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW (July 2011). "Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1". Journal of Virology. 85 (14): 6955–62. doi:10.1128/JVI.00007-11. PMC 3126571. PMID 21593151.

[pmid10022833-10] De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". The EMBO Journal. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.

[pmid11297560-11] Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". The Journal of Biological Chemistry. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560.

[pmid10585430-12] 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): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430.

[pmid12228220-13] Rui L, Yuan M, Frantz D, Shoelson S, White MF (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". The Journal of Biological Chemistry. 277 (44): 42394–8. doi:10.1074/jbc.C200444200. PMID 12228220.

[pmid10064597-14] Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.

[pmid11713228-15] Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (December 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology. 142 (12): 5286–93. doi:10.1210/endo.142.12.8549. PMID 11713228.

[pmid9202126-16] Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature. 387 (6636): 921–4. Bibcode:1997Natur.387..921E. doi:10.1038/43213. PMID 9202126. S2CID 4347361.

[pmid10455112-17] 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): 24497–502. doi:10.1074/jbc.274.35.24497. PMID 10455112.

[pmid11971965-18] Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Molecular and Cellular Biology. 22 (10): 3316–26. doi:10.1128/mcb.22.10.3316-3326.2002. PMC 133778. PMID 11971965.

[pmid9344848-19] Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.

[pmid9341160-20] Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (October 1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". The Journal of Biological Chemistry. 272 (43): 27178–82. doi:10.1074/jbc.272.43.27178. PMID 9341160.

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Suppressor of cytokine signaling 1

Function

Interactions

See also

References

Further reading