Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

SOCS2 (suppressor of cytokine signaling 2)

Written2007-10Leandro 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)
Updated2015-08Indranil Paul, Leandro Fernández-Pérez, Amilcar Flores-Morales
Institut for Veteriaer Sygdomsbiologi, Danish Cancer Society Research Center, University of Copenhagen, Denmark (IP, AFM); 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)

Abstract Review on SOCS2, with data on DNA, on the protein encoded, and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)STATI2
SSI2
SOCS-2
SSI-2
CIS2
Cish2
HGNC (Hugo) SOCS2
LocusID (NCBI) 8835
Atlas_Id 44123
Location 12q21.3-q23 (Yandava et al., 1999). Plus strand.  [Link to chromosome band 12q21]
Location_base_pair Starts at 93964175 and ends at 93970521 bp from pter ( according to hg19-Feb_2009)  [Mapping SOCS2.png]
Fusion genes
(updated 2016)
TMEM116 (12q24.13) / SOCS2 (12q22)WTAP (6q25.3) / SOCS2 (12q22)

DNA/RNA

Description NCBI Reference Sequence: NC_000012.12; Coding positions from 93,966,674 to 93,968,952 (length: 2,279 bp). Mouse SOCS2 gene is composed of 3 exons and 2 introns (Metcalf et al., 2000). Human SOCS-2 comprises 3 exons spanning approximately 6,38 kb of genomic DNA.
Transcription 2888 bp mRNA. There are 6 transcript variants. Transcript variant 5 is the largest and is cited here. The variants differ in their 5' UTR. All variants encode the same protein.

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 Reference sequence for SOCS2 protein: NP_001257399.1. SOCS2 contains 198 amino acid residues with a molecular weight of 22172 Da.
SOCS2 belongs to the SOCS box family. SOCS2 contains a C terminal SOCS box (residue 151-197) for ElonginB,C/Cullin5/Rbx2 interaction. The unstructured N-terminal region (residue 1-47) and the SH2 domain (residue 48-156) is implicated in substrate interaction. The SH2 domain is known to interact with conserved phosphotyrosine residues on target proteins imparting substrate specificity to SOCS box proteins.
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. 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.
Localisation Intracellular, cytoplasm. SOCS2 can be located in the nuclear compartment when overexpressed in cell cultures.
Function The function of SOCS proteins rely, on one hand, in their ability to bind tyrosine phosphorylated proteins through their SH2 domains and, on the other hand, to bind Elongins B/C through their SOCS box domains which in turn engages with the Cullin5/Rbx2 complex to assemble an E3 ubiquitin ligase. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction (Rico-Bautista et al., 2006). Being a substrate recognition module for Cullin5/Rbx2 E3 ligase complex, SOCS2 is involved in regulating protein turnover by targeting proteins for proteasome-mediated degradation. SOCS2 binds and promote the ubiquitination of the Growth Hormone receptor (GHR) controlling GHR content in different tissues (Metcalf et al., 2000; Vesterlund et al., 2011). Through the negative regulation of GHR signaling, SOCS2 exerts multiple actions in growth and metabolisms (Greenhalgh et al., 2005; Zadjali et al., 2012). SOCS2 is also a critical regulator of inflammatory responses and immune cell differentiation (Machado et al., 2006; Hu et al., 2009a). Recently, SOCS2 is being implicated in the progression of multiple human cancers (Schultheis et al., 2002; Harris et al., 2006; Newton et al., 2010; Iglesias-Gato et al., 2014).
Homology HomoloGene (NCBI) Genes identified as putative homologs: NP_003868.1 SOCS2, H.sapiens; XP_001139989.1 SOCS2, P.troglodytes; XP_002798772.1 SOCS2, M.mulatta; XP_005629280.1 SOCS2, C.lupus; NP_803489.1 SOCS2, B.taurus; NP_001162126.1 Socs2, M.musculus; NP_478115.1 Socs2, R.norvegicus; NP_989871.1 SOCS2, G.gallus; NP_001120898.1 socs2, X.tropicalis; NP_001108022.1 socs2, D.rerio

Mutations

Note There are 8 SNPs in coding regions of human SOCS2 which result in missense protein residues (NCBI dbSNP). Homozygous null mice display gigantism (Metcalf et al., 2000), impaired innate immune cell differentiation and hypersensitivity to infections (Baetz et al., 2004; Yoshimura et al., 2005; Yoshimura et al., 2007). Homozygous null mice also display altered metabolic and inflammatory response to high fat feeding (Zadjali et al., 2012;). SNP: increasing the risk of type 2 diabetes (Kato et al., 2006)

Implicated in

Note
Entity Neural development
Note SOCS2 plays a critical role in neuronal development, growth, and stem cell differentiation (Turnley et al., 2002).
  
Entity Inflammation
Note SOCS2 deficient dendritic cells and macrophages are hyper-responsive to microbial stimulation. SOCS2 deficient animals have uncontrolled production of inflammatory cytokines (IL-12, IFNγand TNFα ) and succumb to endotoxic shock, polymicrobial sepsis and other microbial infections (Esper et al., 2012). SOCS2 plays a central role in differentiation and maturation of innate immune cells. Specifically, SOCS2 promotes generation of regulatory dendritic cells and macrophages (Novak et al., 1999; Jackson et al., 2004; Hu et al., 2012) and Treg population (Knosp et al., 2013). Conversely, SOCS2 inhibits Th2 differentiation (Knosp et al., 2011). Upon induced inflammatory challenge, absence of SOCS2 has been shown to render multiple immune cell types incapable of mounting anti-inflammatory responses. Under resting conditions, SOCS2 null animals also display a population-bias towards a pro-inflammatory phenotype (Machado et al., 2006; Lee et al., 2010; Knosp et al., 2011; Posselt et al., 2011; Hu et al., 2012).
SOCS2 is known to inhibit TGFβ, IL-4, IL-5, IL-10, IL-13 and IFNγ signaling (Knosp et al., 2011, Knosp et al., 2013). In general, SOCS2 inhibits expression/secretion of pro-inflammatory cytokines and promotes generation of regulatory phenotype (anti-inflammatory) of immune cells. SOCS2 is thought to function in both MyD88 dependent and independent TLR4 signaling pathways because its downregulation negatively affects SAPK/JNK, p38 MAPK, ERK and NFkB signaling (Hu et al., 2009b). Being an E3 ligase, SOCS2 regulates a number of proteins highly implicated in regulation of immune responses such as FoxP3 (Knosp et al., 2013) and TRAF6 (McBerry et al., 2012). SOCS2 also accelerates degradation of other members of the SOCS family such as SOCS1 and SOCS3 thus further impinging on downstream STAT signaling (Piessevaux et al., 2006; Tannahill et al., 2005). In turn, SOCS2 gene itself is under regulation of various inflammatory signals (e.g., LPS, dioxins, LipoxinA4) (Machado et al., 2006; Hu et al., 2009b, 2012) and cytokines (e.g.,IL-4, IL-10, IFNβ, IFNγ) (Knosp et al., 2011; Posselt et al., 2011).
  
Entity Breast cancer
Note SOCS2 expression inversely correlates with histological grades and is a positive prognostic factor (Farabegoli et al., 2005; Haffner et al., 2007). SOCS2 expression is induced by estrogen receptor (ER) activity. Estrogen treatment activates ER which in turn upregulates miR-191 which through downregulation of SATB1, a global chromatic remodeller, enhances SOCS2 transcription (Nagpal et al., 2013). Upregulation of SOCS2 upon estrogen administration antagonizes growth hormone action mediated through JAK2/STAT3 and STAT5 (Leung et al., 2003).
  
Entity Colon cancer
Note Both heterozygous and homozygous deletions of SOCS2 promoted spontaneous tumorigenesis in ApcMin/+ mice model of colorectal cancer. This is accompanied with a dramatic increase in AP-1 DNA binding (Newton et al., 2010). Acromegalic patients are prone to colonic polyp formation. These patients with hyperplastic polyps have increased SOCS2 transcripts (Bogazzi et al., 2009).
  
Entity Myeloproliferative disorder
Note SOCS2 gene is also hypermethylated in myeloproliferative disorders (Zhou et al., 2009; Zhang et al., 2013). SOCS2 is an important negative regulator of a constitutive active mutant of JAK2 (JAK2 V617F) (Etienne et al., 2007).
  
Entity Prostate cancer
Note SOCS2 is upregulated at both mRNA and protein levels in primary prostate cancer tissues relative to normal prostate. This upregulation is correlated to lower Gleason score, absence of metastasis and low PSA failure (Zhu et al., 2013). In contrast, SOCS2 expression is downregulated in castration resistant prostate cancer. This is partly explained by the fact that SOCS2 is transcriptionally upregulated by androgen receptor and inhibits GH signaling in prostate (Iglesias-Gato et al., 2014).
  
Entity Other cancers
Note SOCS2 gene is hypermethylated in melanoma and ovarian carcinoma (Marini et al., 2006; Liu et al., 2008). Lower SOCS2 expressions are also correlated to higher grades of hepatocellular carcinoma (Qiu et al., 2013).
  
Entity Gigantism
Note SOCS2 null mice are giants but not obese (Metcalf et al., 2000). SOCS2 deficient mice have growth and metabolic characteristics that can be related to the enhanced GH actions (Rico-Bautista et al., 2005). On the other hand, the gigantic phenotype displayed by SOCS2 null mice is mechanistically different from that of human acromegalic patients as they do not exhibit increased circulating IGF-1 levels and seems to express reduced levels of GH (Greenhalgh 2005 and Zadjali 2012).
Disease Gigantism is a condition characterized by excessive growth, significantly above average. This is caused due to an overactivation of growth hormone signaling.
  
Entity Diabetes
Note Genomic linkage analysis identified SOCS2 as a susceptibility gene for type 2 diabetes in a cohort of Japanese individuals. In the same study, adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion (Kato et al., 2006). Constitutive SOCS2 expression in mice pancreatic beta cells interferes with proinsulin processing and leads to decreased insulin secretion (Lebrun et al., 2010). In contrast, SOCS2 null mice does not exhibit obvious defects in pancreatic beta cell function. When challenged with high fat diet SOCS2 null mice are protected from hepatic steatosis but exhibit an exacerbated inflammatory response and a worsening of insulin sensitivity as compared to wild-type mice on a similar diet.
Disease Diabetes is a condition characterized by high blood sugar levels. This is caused due to inadequate insulin production or insulin resistance.
  
Entity Osteoarthritis
Note Analysis of SOCS2 null mice has 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).
Disease Osteoarthritis is a condition characterized by mechanical degeneration of joints resulting in pain and restricted movement. This is caused due to hereditary and metabolic reasons.
  

Bibliography

Suppressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like receptor signaling in innate immune cells
Baetz A, Frey M, Heeg K, Dalpke AH
J Biol Chem 2004 Dec 24;279(52):54708-15
PMID 15491991
 
Changes in the expression of suppressor of cytokine signalling (SOCS) 2 in the colonic mucosa of acromegalic patients are associated with hyperplastic polyps
Bogazzi F, Ultimieri F, Raggi F, Russo D, Costa A, Marciano E, Bartalena L, Martino E
Clin Endocrinol (Oxf) 2009 Jun;70(6):898-906
PMID 18844680
 
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
Mol Pharmacol 2004 Dec;66(6):1662-70
PMID 15371557
 
SOCS: role in inflammation, allergy and homeostasis
Elliott J, Johnston JA
Trends Immunol 2004 Aug;25(8):434-40
PMID 15275643
 
Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease
Esper L, Roman-Campos D, Lara A, Brant F, Castro LL, Barroso A, Araujo RR, Vieira LQ, Mukherjee S, Gomes ER, Rocha NN, Ramos IP, Lisanti MP, Campos CF, Arantes RM, Guatimosim S, Weiss LM, Cruz JS, Tanowitz HB, Teixeira MM, Machado FS
Am J Pathol 2012 Jul;181(1):130-40
PMID 22658486
 
Rearrangements involving 12q in myeloproliferative disorders: possible role of HMGA2 and SOCS2 genes
Etienne A, Carbuccia N, Adélaïde J, Bekhouche I, Rémy V, Sohn C, Sainty D, Gastaut JA, Olschwang S, Birnbaum D, Mozziconacci MJ, Chaffanet M
Cancer Genet Cytogenet 2007 Jul 1;176(1):80-8
PMID 17574970
 
Suppressor of cytokine signalling 2 (SOCS-2) expression in breast carcinoma
Farabegoli F, Ceccarelli C, Santini D, Taffurelli M
J Clin Pathol 2005 Oct;58(10):1046-50
PMID 16189149
 
SOCS2 negatively regulates growth hormone action in vitro and in vivo
Greenhalgh CJ, Rico-Bautista E, Lorentzon M, Thaus AL, Morgan PO, Willson TA, Zervoudakis P, Metcalf D, Street I, Nicola NA, Nash AD, Fabri LJ, Norstedt G, Ohlsson C, Flores-Morales A, Alexander WS, Hilton DJ
J Clin Invest 2005 Feb;115(2):397-406
PMID 15690087
 
Favorable prognostic value of SOCS2 and IGF-I in breast cancer
Haffner MC, Petridou B, Peyrat JP, Révillion F, Müller-Holzner E, Daxenbichler G, Marth C, Doppler W
BMC Cancer 2007 Jul 25;7:136
PMID 17651480
 
Socs2 and elf5 mediate prolactin-induced mammary gland development
Harris J, Stanford PM, Sutherland K, Oakes SR, Naylor MJ, Robertson FG, Blazek KD, Kazlauskas M, Hilton HN, Wittlin S, Alexander WS, Lindeman GJ, Visvader JE, Ormandy CJ
Mol Endocrinol 2006 May;20(5):1177-87
PMID 16469767
 
LPS regulates SOCS2 transcription in a type I interferon dependent autocrine-paracrine loop
Hu J, Lou D, Carow B, Winerdal ME, Rottenberg M, Wikström AC, Norstedt G, Winqvist O
PLoS One 2012;7(1):e30166
PMID 22291912
 
SOCS2 influences LPS induced human monocyte-derived dendritic cell maturation
Hu J, Winqvist O, Flores-Morales A, Wikström AC, Norstedt G
PLoS One 2009 Sep 25;4(9):e7178
PMID 19779605
 
SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer
Iglesias-Gato D, Chuan YC, Wikström P, Augsten S, Jiang N, Niu Y, Seipel A, Danneman D, Vermeij M, Fernandez-Perez L, Jenster G, Egevad L, Norstedt G, Flores-Morales A
Carcinogenesis 2014 Jan;35(1):24-33
PMID 24031028
 
Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling
Jackson SH, Yu CR, Mahdi RM, Ebong S, Egwuagu CE
J Immunol 2004 Feb 15;172(4):2307-15
PMID 14764699
 
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 Apr;87(4):446-58
PMID 16406727
 
SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses
Knosp CA, Carroll HP, Elliott J, Saunders SP, Nel HJ, Amu S, Pratt JC, Spence S, Doran E, Cooke N, Jackson R, Swift J, Fitzgerald DC, Heaney LG, Fallon PG, Kissenpfennig A, Johnston JA
J Exp Med 2011 Jul 4;208(7):1523-31
PMID 21646394
 
Regulation of Foxp3+ inducible regulatory T cell stability by SOCS2
Knosp CA, Schiering C, Spence S, Carroll HP, Nel HJ, Osbourn M, Jackson R, Lyubomska O, Malissen B, Ingram R, Fitzgerald DC, Powrie F, Fallon PG, Johnston JA, Kissenpfennig A
J Immunol 2013 Apr 1;190(7):3235-45
PMID 23455506
 
The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion
Lebrun P, Cognard E, Gontard P, Bellon-Paul R, Filloux C, Berthault MF, Magnan C, Ruberte J, Luppo M, Pujol A, Pachera N, Herchuelz A, Bosch F, Van Obberghen E
Diabetologia 2010 Sep;53(9):1935-46
PMID 20499047
 
Suppressor of cytokine signaling 2 regulates IL-15-primed human NK cell function via control of phosphorylated Pyk2
Lee SH, Yun S, Piao ZH, Jeong M, Kim DO, Jung H, Lee J, Kim MJ, Kim MS, Chung JW, Kim TD, Yoon SR, Greenberg PD, Choi I
J Immunol 2010 Jul 15;185(2):917-28
PMID 20543098
 
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2
Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK
Proc Natl Acad Sci U S A 2003 Feb 4;100(3):1016-21
PMID 12552091
 
Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling
Liu S, Ren S, Howell P, Fodstad O, Riker AI
Pigment Cell Melanoma Res 2008 Oct;21(5):545-58
PMID 18627528
 
Reduced bone mineral density in SOCS-2-deficient mice
Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C
Pediatr Res 2005 Feb;57(2):223-6
PMID 15585682
 
Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent
Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J
Nat Med 2006 Mar;12(3):330-4
PMID 16415877
 
Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma
Marini A, Mirmohammadsadegh A, Nambiar S, Gustrau A, Ruzicka T, Hengge UR
J Invest Dermatol 2006 Feb;126(2):422-31
PMID 16374457
 
SOCS2-induced proteasome-dependent TRAF6 degradation: a common anti-inflammatory pathway for control of innate immune responses
McBerry C, Gonzalez RM, Shryock N, Dias A, Aliberti J
PLoS One 2012;7(6):e38384
PMID 22693634
 
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 Jun 29;405(6790):1069-73
PMID 10890450
 
MicroRNA-191, an estrogen-responsive microRNA, functions as an oncogenic regulator in human breast cancer
Nagpal N, Ahmad HM, Molparia B, Kulshreshtha R
Carcinogenesis 2013 Aug;34(8):1889-99
PMID 23542418
 
Suppressor of cytokine signaling-2 gene disruption promotes Apc(Min/+) tumorigenesis and activator protein-1 activation
Newton VA, Ramocki NM, Scull BP, Simmons JG, McNaughton K, Lund PK
Am J Pathol 2010 May;176(5):2320-32
PMID 20348236
 
Differential ability of SOCS proteins to regulate IL-6 and CSF-1 induced macrophage differentiation
Novak U, Marks D, Nicholson SE, Hilton D, Paradiso L
Growth Factors 1999;16(4):305-14
PMID 10427504
 
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
J Cell Physiol 2006 May;207(2):428-36
PMID 16419040
 
Functional cross-modulation between SOCS proteins can stimulate cytokine signaling
Piessevaux J, Lavens D, Montoye T, Wauman J, Catteeuw D, Vandekerckhove J, Belsham D, Peelman F, Tavernier J
J Biol Chem 2006 Nov 3;281(44):32953-66
PMID 16956890
 
Suppressor of cytokine signaling 2 is a feedback inhibitor of TLR-induced activation in human monocyte-derived dendritic cells
Posselt G, Schwarz H, Duschl A, Horejs-Hoeck J
J Immunol 2011 Sep 15;187(6):2875-84
PMID 21844389
 
Reduced expression of SOCS2 and SOCS6 in hepatocellular carcinoma correlates with aggressive tumor progression and poor prognosis
Qiu X, Zheng J, Guo X, Gao X, Liu H, Tu Y, Zhang Y
Mol Cell Biochem 2013 Jun;378(1-2):99-106
PMID 23475171
 
Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions
Rico-Bautista E, Flores-Morales A, Fernández-Pé L
Cytokine Growth Factor Rev 2006 Dec;17(6):431-9
PMID 17070092
 
Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism
Schultheis B, Carapeti-Marootian M, Hochhaus A, Weisser A, Goldman JM, Melo JV
Blood 2002 Mar 1;99(5):1766-75
PMID 11861294
 
SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation
Tannahill GM, Elliott J, Barry AC, Hibbert L, Cacalano NA, Johnston JA
Mol Cell Biol 2005 Oct;25(20):9115-26
PMID 16199887
 
Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling
Turnley AM, Faux CH, Rietze RL, Coonan JR, Bartlett PF
Nat Neurosci 2002 Nov;5(11):1155-62
PMID 12368809
 
The SOCS2 ubiquitin ligase complex regulates growth hormone receptor levels
Vesterlund M, Zadjali F, Persson T, Nielsen ML, Kessler BM, Norstedt G, Flores-Morales A
PLoS One 2011;6(9):e25358
PMID 21980433
 
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
Mol Endocrinol 2007 Jan;21(1):293-311
PMID 17008382
 
Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively
Yandava CN, Pillari A, Drazen JM
Genomics 1999 Oct 1;61(1):108-11
PMID 10512686
 
SOCS proteins, cytokine signalling and immune regulation
Yoshimura A, Naka T, Kubo M
Nat Rev Immunol 2007 Jun;7(6):454-65
PMID 17525754
 
SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice
Zadjali F, Santana-Farre R, Vesterlund M, Carow B, Mirecki-Garrido M, Hernandez-Hernandez I, Flodström-Tullberg M, Parini P, Rottenberg M, Norstedt G, Fernandez-Perez L, Flores-Morales A
FASEB J 2012 Aug;26(8):3282-91
PMID 22562833
 
Methylation profiling of SOCS1, SOCS2, SOCS3, CISH and SHP1 in Philadelphia-negative myeloproliferative neoplasm
Zhang MY, Fung TK, Chen FY, Chim CS
J Cell Mol Med 2013 Oct;17(10):1282-90
PMID 24131863
 
Enhanced activation of STAT pathways and overexpression of survivin confer resistance to FLT3 inhibitors and could be therapeutic targets in AML
Zhou J, Bi C, Janakakumara JV, Liu SC, Chng WJ, Tay KG, Poon LF, Xie Z, Palaniyandi S, Yu H, Glaser KB, Albert DH, Davidsen SK, Chen CS
Blood 2009 Apr 23;113(17):4052-62
PMID 19144991
 
Expression of SOCSs in human prostate cancer and their association in prognosis
Zhu JG, Dai QS, Han ZD, He HC, Mo RJ, Chen G, Chen YF, Wu YD, Yang SB, Jiang FN, Chen WH, Sun ZL, Zhong WD
Mol Cell Biochem 2013 Sep;381(1-2):51-9
PMID 23666742
 

Citation

This paper should be referenced as such :
Paul I, Fernández-Pérez L, Flores-Morales A
SOCS2 (suppressor of cytokine signaling 2);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/SOCS2ID44123ch12q21.html
History of this paper:
Fernandez-Pérez, L ; Flores-Morales, A. SOCS2 (suppressor of cytokine signaling 2). Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):240-242.
http://documents.irevues.inist.fr/bitstream/handle/2042/38528/10-2007-SOCS2ID44123ch12q21.pdf


External links

Nomenclature
HGNC (Hugo)SOCS2   19382
Cards
AtlasSOCS2ID44123ch12q21
Entrez_Gene (NCBI)SOCS2  8835  suppressor of cytokine signaling 2
AliasesCIS2; Cish2; SOCS-2; SSI-2; 
SSI2; STATI2
GeneCards (Weizmann)SOCS2
Ensembl hg19 (Hinxton)ENSG00000120833 [Gene_View]  chr12:93964175-93970521 [Contig_View]  SOCS2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000120833 [Gene_View]  chr12:93964175-93970521 [Contig_View]  SOCS2 [Vega]
ICGC DataPortalENSG00000120833
TCGA cBioPortalSOCS2
AceView (NCBI)SOCS2
Genatlas (Paris)SOCS2
WikiGenes8835
SOURCE (Princeton)SOCS2
Genetics Home Reference (NIH)SOCS2
Genomic and cartography
GoldenPath hg19 (UCSC)SOCS2  -     chr12:93964175-93970521 +  12q   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SOCS2  -     12q   [Description]    (hg38-Dec_2013)
EnsemblSOCS2 - 12q [CytoView hg19]  SOCS2 - 12q [CytoView hg38]
Mapping of homologs : NCBISOCS2 [Mapview hg19]  SOCS2 [Mapview hg38]
OMIM605117   
Gene and transcription
Genbank (Entrez)AB004903 AB006966 AB451318 AF020590 AF037989
RefSeq transcript (Entrez)NM_001270467 NM_001270468 NM_001270469 NM_001270470 NM_001270471 NM_003877
RefSeq genomic (Entrez)NC_000012 NC_018923 NT_029419 NW_004929384
Consensus coding sequences : CCDS (NCBI)SOCS2
Cluster EST : UnigeneHs.737206 [ NCBI ]
CGAP (NCI)Hs.737206
Alternative Splicing GalleryENSG00000120833
Gene ExpressionSOCS2 [ NCBI-GEO ]   SOCS2 [ EBI - ARRAY_EXPRESS ]   SOCS2 [ SEEK ]   SOCS2 [ MEM ]
Gene Expression Viewer (FireBrowse)SOCS2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8835
GTEX Portal (Tissue expression)SOCS2
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14508   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14508  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14508
Splice isoforms : SwissVarO14508
PhosPhoSitePlusO14508
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SOCS (PS50225)   
Domains : Interpro (EBI)SH2    SOCS2    SOCS_box   
Domain families : Pfam (Sanger)SH2 (PF00017)    SOCS_box (PF07525)   
Domain families : Pfam (NCBI)pfam00017    pfam07525   
Domain families : Smart (EMBL)SH2 (SM00252)  SOCS (SM00253)  SOCS_box (SM00969)  
Conserved Domain (NCBI)SOCS2
DMDM Disease mutations8835
Blocks (Seattle)SOCS2
PDB (SRS)2C9W    4JGH    5BO4   
PDB (PDBSum)2C9W    4JGH    5BO4   
PDB (IMB)2C9W    4JGH    5BO4   
PDB (RSDB)2C9W    4JGH    5BO4   
Structural Biology KnowledgeBase2C9W    4JGH    5BO4   
SCOP (Structural Classification of Proteins)2C9W    4JGH    5BO4   
CATH (Classification of proteins structures)2C9W    4JGH    5BO4   
SuperfamilyO14508
Human Protein AtlasENSG00000120833
Peptide AtlasO14508
HPRD05490
IPIIPI00033944   IPI01010199   IPI01020907   IPI01022880   IPI01021714   IPI00978442   
Protein Interaction databases
DIP (DOE-UCLA)O14508
IntAct (EBI)O14508
FunCoupENSG00000120833
BioGRIDSOCS2
STRING (EMBL)SOCS2
ZODIACSOCS2
Ontologies - Pathways
QuickGOO14508
Ontology : AmiGOregulation of cell growth  protein kinase inhibitor activity  SH3/SH2 adaptor activity  growth hormone receptor binding  insulin-like growth factor receptor binding  protein binding  cytoplasm  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  JAK pathway signal transduction adaptor activity  regulation of signal transduction  positive regulation of signal transduction  protein ubiquitination  cytokine-mediated signaling pathway  response to estradiol  cellular response to hormone stimulus  negative regulation of apoptotic process  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  growth hormone receptor signaling pathway  
Ontology : EGO-EBIregulation of cell growth  protein kinase inhibitor activity  SH3/SH2 adaptor activity  growth hormone receptor binding  insulin-like growth factor receptor binding  protein binding  cytoplasm  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  JAK pathway signal transduction adaptor activity  regulation of signal transduction  positive regulation of signal transduction  protein ubiquitination  cytokine-mediated signaling pathway  response to estradiol  cellular response to hormone stimulus  negative regulation of apoptotic process  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  growth hormone receptor signaling pathway  
Pathways : KEGGJak-STAT signaling pathway    Insulin signaling pathway    Prolactin signaling pathway    Type II diabetes mellitus   
REACTOMEO14508 [protein]
REACTOME PathwaysR-HSA-982772 Growth hormone receptor signaling [pathway]
NDEx NetworkSOCS2
Atlas of Cancer Signalling NetworkSOCS2
Wikipedia pathwaysSOCS2
Orthology - Evolution
OrthoDB8835
GeneTree (enSembl)ENSG00000120833
Phylogenetic Trees/Animal Genes : TreeFamSOCS2
HOVERGENO14508
HOGENOMO14508
Homologs : HomoloGeneSOCS2
Homology/Alignments : Family Browser (UCSC)SOCS2
Gene fusions - Rearrangements
Fusion : MitelmanWTAP/SOCS2 [6q25.3/12q22]  [t(6;12)(q25;q22)]  
Fusion: TCGAWTAP 6q25.3 SOCS2 12q22 PRAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSOCS2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SOCS2
dbVarSOCS2
ClinVarSOCS2
1000_GenomesSOCS2 
Exome Variant ServerSOCS2
ExAC (Exome Aggregation Consortium)SOCS2 (select the gene name)
Genetic variants : HAPMAP8835
Genomic Variants (DGV)SOCS2 [DGVbeta]
DECIPHER (Syndromes)12:93964175-93970521  ENSG00000120833
CONAN: Copy Number AnalysisSOCS2 
Mutations
ICGC Data PortalSOCS2 
TCGA Data PortalSOCS2 
Broad Tumor PortalSOCS2
OASIS PortalSOCS2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSOCS2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSOCS2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SOCS2
DgiDB (Drug Gene Interaction Database)SOCS2
DoCM (Curated mutations)SOCS2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SOCS2 (select a term)
intoGenSOCS2
NCG5 (London)SOCS2
Cancer3DSOCS2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605117   
Orphanet
MedgenSOCS2
Genetic Testing Registry SOCS2
NextProtO14508 [Medical]
TSGene8835
GENETestsSOCS2
Huge Navigator SOCS2 [HugePedia]
snp3D : Map Gene to Disease8835
BioCentury BCIQSOCS2
ClinGenSOCS2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8835
Chemical/Pharm GKB GenePA128394542
Clinical trialSOCS2
Miscellaneous
canSAR (ICR)SOCS2 (select the gene name)
Probes
Litterature
PubMed92 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSOCS2
EVEXSOCS2
GoPubMedSOCS2
iHOPSOCS2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Nov 18 20:03:57 CET 2016

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.