Atlas of Genetics and Cytogenetics in Oncology and Haematology
SOCS2 (suppressor of cytokine signaling 2)
| Identity |
| Other names | CIS-2, Cytokine-inducible SH2 protein 2 |
| CIS2, STAT induced STAT inhibitor-2 | |
| Cish2, STAT-induced STAT inhibitor 2 | |
| SOCS-2, suppressor of cytokine signaling 2 | |
| SSI-2, suppressor of cytokine signaling-2 | |
| SSI2 | |
| STATI2 | |
| HGNC | SOCS2 |
| Location | 12q21.33 |
| Location_base_pair | Starts at 92487729 and ends at 92494109 bp from pter ( according to hg18-Mar_2006). |
| Local_order | By cytogenetic and radiation hybrid mapping, SOCS-2 has been mapped to chromosome 12q21.3-q23 (Yandava et al., 1999). |
| DNA/RNA |
| Description | 6,38 kb ; 3 Exons. Mouse SOCS2 gene is composed of 3 exons and 2 introns (Metcalf et al., 2000). Human SOCS-2 is a functioning gene that comprises 3 exons spanning roughly 6,38 kb of genomic DNA. |
| Transcription | 2210 bp mRNA. 1 protein (22.2 kDa; 198 aa). Although constitutively expressed SOCS2 mRNA has been detected in several tissues and cell types, its expression is, in general, induced by stimulation with different cytokines and hormones (Rico-Bautista et al., 2006). SOCS2 promoter analysis indicates the presence of AhR and STAT5 binding sites that confer responsiveness to dioxin (Boverhof et al., 2004) and GH (Vidal et al., 2006), respectively. |
| Protein |
 | |
| Diagram representing the structure of SOCS proteins. At least eight proteins belonging to the SOCS family of proteins are shown (upper panel). They are characterized by the presence of an SH2 central domain and the SOCS box domain at the C-terminus. A small domain called kinase inhibitory region (KIR), only found in SOCS1 and SOCS3, is shown as a small box at the N-terminal region. SOCS proteins can interact with phosphotyrosine phosphorylated proteins through their SH2 domain and with Elongin BC through their SOCS box domain. Other proteins containing a SOCS box domain but lacking a SH2 domain are also shown (lower panel). Adapted from Elliot and Johnston (Elliott and Johnston, 2004) with modifications. | |
| Description | 22.2 kDa; 198 aa. |
| Expression | SOCS mRNA and protein levels are constitutively low in unstimulated cells, but their expression is rapidly induced upon cytokine stimulation, thereby creating a negative feedback loop. Its expression is, in general, induced by stimulation with different cytokines and hormones (Rico-Bautista et al., 2006). |
| Localisation | Intracellular, cytoplasm. |
| Function | SOCS mechanisms of action rely on their ability to bind tyrosine phosphorylated proteins through their SH2 domains, but also to bind Elongin BC through their SOCS box domains. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction (Rico-Bautista et al., 2006). SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway (Metcalf et al., 2000). SOCS2 appear to be involved in regulating protein turnover, targeting proteins for proteasome-mediated degradation (Rico-Bautista et al., 2004). |
| Mutations |
| Note | SNP: increasing the risk of type 2 diabetes. |
| Implicated in |
| Entity | Diabete |
| Note | Susceptibility: to type 2 diabetes (Kato et al., 2006). |
| Entity | Metabolism |
| Note | SOCS2 null mice are giants but not obese (Metcalf et al., 2000). SOCS2 deficient mice have some metabolic characteristics that can be related to the enhanced GH actions (Rico-Bautista et al., 2005). |
| Entity | Bone |
| Note | Analysis of SOCS2 null mice have revealed that the absence of SOCS2 induces a reduction in the trabecular and cortical volumetric bone mineral density (Lorentzon et al., 2005). SOCS2 induces the differentiation of C2C12 mesenchymal cells into myoblasts or osteoblasts (Ouyang et al., 2006). |
| Entity | Neural development |
| Note | SOCS2 plays a critical role in neuronal development, growth, and stem cell differentiation (Turnley et al., 2002). |
| Entity | Cancer |
| Note | SOCS2 has been associated with cancer such as myeloid leukaemia, pulmonary adenocarcinoma, and ovarian cancer, breast cancer, and anal cancer. |
| External links |
| Bibliography |
| Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively. |
| Yandava CN, Pillari A, Drazen JM |
| Genomics. 1999 ; 61 (1) : 108-111. |
| PMID 10512686 |
| Gigantism in mice lacking suppressor of cytokine signalling-2. |
| Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS |
| Nature. 2000 ; 405 (6790) : 1069-1073. |
| PMID 10890450 |
| Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. |
| Turnley AM, Faux CH, Rietze RL, Coonan JR, Bartlett PF |
| Nature neuroscience. 2002 ; 5 (11) : 1155-1162. |
| PMID 12368809 |
| 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. |
| Boverhof DR, Tam E, Harney AS, Crawford RB, Kaminski NE, Zacharewski TR |
| Molecular pharmacology. 2004 ; 66 (6) : 1662-1670. |
| PMID 15371557 |
| SOCS: role in inflammation, allergy and homeostasis. |
| Elliott J, Johnston JA |
| Trends in immunology. 2004 ; 25 (8) : 434-440. |
| PMID 15275643 |
| Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton. |
| Rico-Bautista E, Negrˆ‚n-Martˆ‚nez C, Novoa-Mogollˆ„n J, Fernˆ°ndez-Perez L, Flores-Morales A |
| Experimental cell research. 2004 ; 294 (1) : 269-280. |
| PMID 14980520 |
| Reduced bone mineral density in SOCS-2-deficient mice. |
| Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C |
| Pediatric research. 2005 ; 57 (2) : 223-226. |
| PMID 15585682 |
| Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects. |
| Rico-Bautista E, Greenhalgh CJ, Tollet-Egnell P, Hilton DJ, Alexander WS, Norstedt G, Flores-Morales A |
| Molecular endocrinology (Baltimore, Md.). 2005 ; 19 (3) : 781-793. |
| PMID 15563548 |
| Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese. |
| Kato H, Nomura K, Osabe D, Shinohara S, Mizumori O, Katashima R, Iwasaki S, Nishimura K, Yoshino M, Kobori M, Ichiishi E, Nakamura N, Yoshikawa T, Tanahashi T, Keshavarz P, Kunika K, Moritani M, Kudo E, Tsugawa K, Takata Y, Hamada D, Yasui N, Miyamoto T, Shiota H, Inoue H, Itakura M |
| Genomics. 2006 ; 87 (4) : 446-458. |
| PMID 16406727 |
| SOCS-2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cells. |
| Ouyang X, Fujimoto M, Nakagawa R, Serada S, Tanaka T, Nomura S, Kawase I, Kishimoto T, Naka T |
| Journal of cellular physiology. 2006 ; 207 (2) : 428-436. |
| PMID 16419040 |
| Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. |
| Rico-Bautista E, Flores-Morales A, Fernˆ°ndez-Pˆ©rez L |
| Cytokine & growth factor reviews. 2006 ; 17 (6) : 431-439. |
| PMID 17070092 |
| In vivo transcript profiling and phylogenetic analysis identifies suppressor of cytokine signaling 2 as a direct signal transducer and activator of transcription 5b target in liver. |
| Vidal OM, Merino R, Rico-Bautista E, Fernandez-Perez L, Chia DJ, Woelfle J, Ono M, Lenhard B, Norstedt G, Rotwein P, Flores-Morales A |
| Molecular endocrinology (Baltimore, Md.). 2007 ; 21 (1) : 293-311. |
| PMID 17008382 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 10-2007 | Leandro Fernández-Pérez, Amilcar Flores-Morales |
| University of Las Palmas de GC, Faculty of Health Sciences, Molecular and Translational Endocrinology Group, c/ Dr. Pasteur s/n - Campus San Cristobal, 35016 - Las Palmas, Spain, (LFP); Department of Molecular Medicine and Surgery, Karolinska Institute, 17176 Stockholm, Sweden (AFM) |
| Citation |
| This paper should be referenced as such : |
| Fernández-Pérez L, Flores-Morales A . SOCS2 (suppressor of cytokine signaling 2). Atlas Genet Cytogenet Oncol Haematol. October 2007 . URL : http://AtlasGeneticsOncology.org/Genes/SOCS2ID44123ch12q21.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Nov 27 13:29:39 2008 |
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