SNCG (synuclein, gamma (breast cancer-specific protein 1))

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home Genes Leukemias Solid Tumors 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

SNCG (synuclein, gamma (breast cancer-specific protein 1))

Written	2014-06	Andrei Surguchov
		Department of Neurology, Kansas University Medical Center, Kansas City, KS, VA Medical Center, Kansas City, MO, USA

This article is an update of :

	2007-06	Artur Czekierdowski, Sylwia Czekierdowska
		Ist Dept. of Gynecologic Oncology, Gynecology, Medical University in Lublin, Poland (AC); Dept. of Clinical Immunology, Medical University in Lublin, Poland (SC)

Abstract

Expression of synuclein-gamma (SNCG) protein is elevated in the advanced stages of many types of cancers, including breast, ovarian, lung, gastric, liver, esophagus, colon, prostate and others. In breast carcinoma, SNCG is causatively linked to stimulated proliferation, metastasis and drug resistance. A clinical follow-up study indicates that patients with an SNCG-positive breast cancer have a significantly shorter disease-free survival and overall survival than patients with SNCG-negative tumors. Overexpression of SNCG compromises normal mitotic checkpoint controls, resulting in multinucleation as well as faster cell growth. SNCG has also been shown to promote invasion and metastasis in in vitro assays as well as in animal models. SNCG overexpression also interferes with drug-induced apoptotic responses. Expression of SNCG in cancer cells results in a more malignant phenotype with increased cell motility, enhanced transcriptional activity of steroid receptors and accelerated rate of chromosomal instability. Two closely located AP1 binding sites residing in the first intron of the SNCG gene are important regulators of the promoter activity. Other factors regulating SNCG expression are methylation-demethylation of exon and post-transcriptional regulation by microRNAs.

Keywords

Invasion, metastasis, cancer, tumorigenesis, transcriptional regulation, microRNA

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)	BCSG1
	gamma-synuclein
	PERSYN
	PRSN
	Synoretin
HGNC (Hugo)	SNCG
HGNC Alias symb	BCSG1
	SR
	persyn
HGNC Alias name	synoretin
	breast cancer-specific gene 1
	?�-synuclein
LocusID (NCBI)	6623
Atlas_Id	42343
Location	10q23.2 [Link to chromosome band 10q23]
Location_base_pair	Starts at 86958599 and ends at 86963258 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping SNCG.png]

Fusion genes
(updated 2017)

Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

SNCG (10q23.2) / ZNF785 (16p11.2)

Note	Synuclein-gamma is a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. High levels of SNCG have been identified in several types of cancer suggesting the association of its overexpression and cancer development.

DNA/RNA

Description

Human SNCG gene consists of five exons that span about 5 kbp. The intron 1 contains two closely located AP1 recognition sequences. Deletion of these motifs greatly diminished the SNCG promoter activity, suggesting that AP1 is an important transactivator for SNCG transcription SNCG transcription is primarily controlled by regulatory sequences located in intron 1 and exon 1 and in a lesser extent by 5' flanking region. Synuclein expression is regulated predominantly at the level of SNCG gene transcription, SNCG mRNA stability and by micro-RNA (miRs).

Protein

Description	Encoded by human SNCG gene (synuclein family), the highly conserved 127-amino acid 13 kD cytoplasmic gamma-synuclein is similar to two other members of the family, alpha-synuclein and beta-synuclein. The gamma-synuclein protein is the least conserved of the synuclein proteins. The human gamma-synuclein is 87.7% and 83.8% identical to the mouse and rat proteins, respectively, which are 4-amino acids shorter. For all three members of the family the region of highest homology is the amino-terminal region. The synuclein proteins contain several repeated domains that display variations of a KTKEGV consensus sequence. This motif, repeated six to seven times in the amino-terminal portion of the protein, is reminiscent of the alpha-helical domains of the apolipoproteins and suggests lipid binding properties. The very high conservation between species for a specific repeated domain of a particular protein suggests that the repeated domains have arisen from the duplication of a single domain within an ancestral synuclein gene. Later, this ancestral gene may have undergone successive duplications to give rise to the three synuclein genes in which the repeated domains may still be able to diverge. The third domain, however, remained absolutely identical, KTKEGV, in all genes throughout all species. A similar type of domain is present in proteins of the rho family. However, as of today, the role of these domains remains unknown.
Expression	Mammalian gamma-synuclein was first identified as the so-called breast cancer-specific gene 1 (BCSG1) in a high-throughput direct differential-cDNA-sequencing screen for markers of breast cancer. Northern blot analysis showed that the gene is principally expressed in the brain, particularly in the substantia nigra. The protein is expressed in the peripheral nervous system, mainly in primary sensory neurons, sympathetic neurons, and motor neurons. A high level of synuclein gamma was also detected in several types of tumors, and in the olfactory epithelium. A sequence dubbed synoretin was independently isolated from ocular tissues in a screen for novel proteins regulating phototransduction and is now thought to represent the bovine ortholog of gamma-synuclein. SNCG is expressed in brain, heart, skeletal muscle, ovary, testis, colon, spleen, pancreas, kidney and lung. MicroRNAs (miRs) are implicated in the regulation of SNCG expression.
Localisation	The three human synuclein genes are expressed in the thalamus, the substantia nigra, the caudate nucleus, and the amygdala. Only gamma-synuclein appears strongly expressed in the subthalamic nucleus. Although gamma-synuclein is not present in senile plaques, Lewy bodies or neurofibrillary tangles, a high level of gamma-synuclein immunoreactivity is detectable in dot-like structures and other deposits which are characteristic lesions in the brains of patients with neurodegenerative diseases, as well as in the retina and optic nerve. SNCG mRNA and gamma-synuclein protein were also detected in unstimulated and phytohaemagglutinin (PHA)-stimulated cultured lymphocytes from peripheral blood of normal donors. It has been shown previously by in situ hybridization that SNCG/BCSG1 mRNA is not expressed in normal adult breast tissue, but high levels of this mRNA are present in advanced infiltrating breast tumours. In paraformaldehyde fixed cells, SNCG displayed punctuate cytoplasmic staining, a pattern that is usually associated with markers of the endoplasmic reticulum or vesicular structures.
Function	The normal cellular function of gamma-synuclein is as yet unclear, but interestingly exogenous expression of the protein increases the invasive and metastatic potential of breast tumors. The highly conserved N-terminal region is known to be important for the lipid interactions of the synucleins and the highly acidic C-terminal region has been suggested to possess chaperone-like activity, to regulate the aggregation of synucleins and to mediate protein-protein interactions. It seems that gamma-synuclein plays a role in neurofilament network integrity and may modulate axonal architecture, also, it may increase the susceptibility of neurofilament-H to calcium-dependent proteases and may also modulate the keratin network in skin. Phosphorylation by GRK5 appears to occur on residues distinct from other kinase target residues. Synuclein gamma is likely involved in the pathogenesis of neurodegenerative and ocular diseases, for example, glaucoma and SNCG is expressed at very high level in advanced infiltrating breast cancer. The dual role of SNCG in neurodegeneration and malignancy could involve common mechanisms. Changes in organization of the cell cytoskeleton are among the most prominent characteristics of both processes. The involvement of gamma-synuclein in regulating neurofilament network integrity raises the possibility that it may also affect the intermediate filament network in malignant breast epithelial cells. In addition, gamma-synuclein regulates the level of expression of several genes, for example matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). Gamma-synuclein is readily oxidized at methionine-38 and after oxidation it aggregates and induces the aggregation of alpha-synuclein. The binding of gamma-synuclein to phospholipase C β2 (PLCβ2) results in inhibition of enzymatic activity and therefore may regulate the intracellular level of second messenger phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2). Gamma-synuclein is a novel regulator of lipid metabolism in adipocytes and the deficiency of this protein has a significant effect on whole body energy expenditure.
Homology	There are currently almost 200 DNA and protein sequences in the sequence databases with high homology to the synuclein gene or protein. All synuclein sequences available to date from Homo sapiens, Mus musculus, and Rattus norvegicus can be assigned to three distinct protein groups: alpha beta and gamma-synuclein. Synuclein proteins have also been identified in other organisms: synelfin is the alpha-synuclein ortholog in Serinus, phospho-neuroprotein 14 (PNP14) is the beta-synuclein ortholog in Bos taurus, and the first synuclein protein described in Torpedo californica corresponds to the human gamma-synuclein. Interestingly, synucleins are identified only in vertebrate and no homologous proteins have been revealed in invertebrate or lower organisms. Each of the three family members is composed of an N-terminal lipid-binding domain, containing a series of 11-residue imperfect repeats, and an acidic C-terminal domain. Among the human family members, gamma-synuclein 50% identical and 74% homologous to alpha-synuclein and 47% identical and 66% homologous beta-synuclein. The highly conserved N-terminal region is known to be important for the lipid interactions of the synucleins and the highly acidic C-terminal region has been suggested to possess chaperone-like activity, to regulate the aggregation of synuclein and to mediate protein-protein interactions. The very high degree of conservation in the lipid-binding N-terminal domains of all three synucleins strongly suggests that both beta and gamma-synuclein like alpha-synuclein bind to lipid membranes and adopt a highly helical structure. Nevertheless, differences in the sequences of the three proteins in both their central parts and C-terminal domains must be responsible for those differences that do exist in their individual functions, as well as for their different roles in disease.

Mutations

Note

No tumor-specific mutations of the SNCG gene were found in breast tumors and tumor cell lines, but two linked polymorphisms in the coding region were detected, both in mRNA and in exons III and IV of the gene from G243C and T377A. These results reflect the absence of two G--A (and consequently Glu--Lys) in tumor cell lines, tumors and control tissues. The above mentioned two linked polymorphic sites discriminate two alleles of the human persyn gene. The frequencies of the two alleles were the same in genomes of breast cancer and normal cells (20% G243/T377 and 80% C243/A377). Both alleles are transcriptionally active and are expressed with similar efficiency in heterozygotes.

Epigenetics

Sequence analysis identified a CpG island in exon 1 of SNCG that contains 15 CpG sites, covering the region -169 to +81, relative to the translation start codon. CpG sites within the CpG island and its vicinity were partially and heterogeneously methylated in SNCG-negative breast cancer cell lines but unmethylated in SNCG-positive cells. SNCG expression correlates with complete demethylation of the exon 1 region. Specific methylation at the CpG sites 2, 5, 7, and 10-15, was sufficient to block the expression of SNCG gene in breast cell culture. Genomic sequencing and methylation-specific PCR assays have shown that SNCG CpG island is fully methylated in normal tissues of liver, esophagus, prostate, cervix, stomach, colon, and lung, but only partially methylated in breast tissue. Tumors from these tissues contain completely demethylated SNCG. Universal loss of the epigenetic control of SNCG gene expression in tumors and further demonstrating that the demethylation of SNCG CpG island is primarily responsible for the aberrant expression of SNCG protein in cancerous tissues have suggested an important role of gamma-synuclein-related epigenectic events in various malignancies. Reactivation of SNCG gene expression by DNA demethylation is a common critical contributing factor to malignant progression of many solid tumors and its expression in primary carcinomas is an effective molecular indicator of distant metastasis.

Implicated in

Note
Note	The possible involvement of gamma-synuclein in tumorigenesis first came to light when a gene named BCSG1 (breast cancer-specific gene 1) was shown to be overexpressed in advanced infiltrating carcinoma of the breast. In fact, BCSG1 and gamma-synuclein appear to be the same protein. SNCG protein is highly expressed in diversified cancer types, including the female hormone-sensitive cervical and breast cancers, male hormone-sensitive prostate cancer, four cancer types of the digestive system, and lung cancer. These cancers are currently the leading cause of mortality in both men and women. How SNCG induces disease progression in different cancer types remains elusive. Oncogenic activation of gamma-synuclein contributes to the development of breast and ovarian cancer by promoting tumor cell survival under adverse conditions and by providing resistance to certain chemotherapeutic drugs. Overexpression of gamma-synuclein leads to constitutive activation of extracellular signal-regulated protein kinases (ERK1/ERK2) and down-regulation of c-Jun N-terminal kinase 1(JNK1) in response to environmental stress signals. Gamma-synuclein is found in a wide variety of transformed cells and its overexpression leads to a significant increase in proliferation, motility, invasiveness and metastasis. Cells expressing gamma-synuclein are significantly more resistant to the chemotherapeutic drugs paclitaxel and vinblastine as compared with the parental cells. Activation of JNK1 and its downstream caspase-3 by paclitaxel or vinblastine is significantly down-regulated in gamma-synuclein-expressing cells, indicating that the apoptosis pathway activated by vinblastine or paclitaxel is blocked by gamma-synuclein. In breast cancer cells, SNCG has been shown to act as a chaperon for estrogen receptor and stimulate estrogen receptor-a signaling pathway that leads to cell proliferation. On the other hand, the inhibitory effects of SNCG on mitotic checkpoint function are mediated through the mitotic checkpoint kinase BubR1 and are independent of the expression status of estrogen receptor-alpha. The inhibitory effects of SNCG on mitotic checkpoint can be overthrown by enforced overexpression of BubR1 in SNCG-expressing cells. SNCG intracellularly associates with BubR1 together. This observation suggests that SNCG expression compromises the mitotic checkpoint control by inhibition of the normal function of BubR1, thereby promoting genetic instability, a recognized and important contributing factor in tumorigenesis. Because all synucleins have chaperone-like activities, they may interact with different proteins in different cellular background. Identifications of specific cellular targets of SNCG in different tumor types will provide insight to delineate its oncogenic functions in human malignancies.


Entity	Breast cancer
Note	Patients whose tumors expressed SNCG had a significantly shorter disease-free survival and overall survival. They also had a high probability of death when compared with those whose tumors did not express SNCG. Multivariate analysis demonstrated that SNCG is an independent predictive marker for recurrence and metastasis in breast cancer progression. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment. In one study it has been show that responses of 12 breast cancer cell lines to paclitaxel-induced mitotic arrest and cytotoxicity highly correlated with SNCG expression status. SNCG-positive cells exhibited a significantly higher resistance to paclitaxel-induced mitotic arrest than SNCG-negative cells. Down-regulation of SNCG expression directly increased the effectiveness of anti-microtubule drug-induced cytotoxicity in breast cancer cells without altering cell responses to doxorubicin. These new findings suggest that SNCG expression in breast carcinomas is probably a causal factor contributing to the poor patient response to paclitaxel treatment.


Entity	Ovarian cancer
Note	Several studies indicated that SNCG expression was not detectable in normal ovarian epithelium but was highly expressed in the vast majority of advanced staged ovarian carcinomas. Eighty-seven percent of ovarian carcinomas were found to express at least 1 type of synuclein, and 42% expressed all 3 synucleins (alpha, beta, and gamma) simultaneously. Highly punctate gamma synuclein expression was also observed in 20% of preneoplastic lesions of the ovary, including epithelial inclusion cysts, hyperplastic epithelium, and papillary structures, suggesting that synuclein gamma up-regulation may occur early in the development of some ovarian tumors. Demethylation is an important event in abnormal synuclein-gamma expression. The methylation pattern in ovarian cancer cells is different from that in breast cancer cells. In one of the studies that examined SNCG-nonexpressing ovarian cancer cells, all of the CpG sites were completely methylated instead of selective methylation at certain sites shown in breast cancer cells, thereby suggesting a tissue-specific methylation pattern. Recent studies indicated that the detection of SNCG mRNA in tumor-positive tumors was strongly associated with demethylation or hypometylation of SNCG gene. Methylation status was not correlated with FIGO stage or histological type of tumor. Tumor grading was strongly associated with methylation status but due to relatively small group of studied samples (43 cases) this observation requires further confirmation. Another interesting observation was that in 21% of samples both products of amplification were present and all these cases were SNCG mRNA-positive. This observation could suggested that partial methylation of SNCG probably does not influence on synuclein expression in ovarian cancer tissue. Comparison of the methylation status of SNCG and the expression of synuclein-gamma in breast and ovarian cancer cells lines in another study indicated a strong correlation between hypomethylation of the CpG island and SNCG expression in cancer cell lines. The methylation pattern in ovarian cancer cells was different from that in breast cancer cells. The analyzed CpG sites in ovarian cancer cells were all methylated in contrary to a selective methylation at certain sites shown in breast cancer cells, thereby suggesting a tissue-specific methylation pattern. Moreover, when exon 1 was partially and heterogeneously methylated, then SNCG expression in breast cancer cells was not detected.


Entity	Lung cancer
Note	SNCG is not expressed in normal lung tissues, but it is highly expressed in lung tumors. It has been demonstrated that cigarette smoke extract (CSE) has strong inducing effects on SNCG gene expression in lung cancer cells through demethylation of SNCG CpG island. CSE treatment also augments the invasive capacity of cells in an SNCG-dependent manner. These new findings demonstrate that tobacco exposure induces the abnormal expression of SNCG in lung cancer cells through downregulation of expression levels of DNA methyltransferases.


Entity	Gastric cancer
Note	For the gastric cancer cell lines, SNCG mRNA expression strongly correlated with demethylation of SNCG exon 1 CpG islands. Whereas SNCG was not expressed in non-neoplastic gastric mucosal tissues obtained at autopsy, partial demethylation was present in these tissues. Demethylation occurs before malignant transformation and that only partial demethylation does not result in up-regulated SNCG mRNA expression. Thus, it appears that partial SNCG demethylation can occur in normal gastric mucosa, which then extends in some cases to become to fully demethylated, resulting in up-regulated SNCG mRNA expression.


Entity	Esophageal cancer
Note	The examination of the serum γ-synuclein levels of patients with gastrointestinal and esophageal squamous cell carcinomas, benign disease and healthy controls by a sandwich ELISA demonstrated a positive correlation between serum γ-synuclein and the development of these types of cancer. From this study a conclusions was put forward that serum γ-synuclein is a promising diagnostic biomarker for early detection of gastrointestinal and esophageal cancer. Serum γ-synuclein SNCG may play an important role in invasion, infiltration and apoptosis of esophageal cancer and serve as target spots in the targeted therapy of esophageal cancer. However, the analysis of expression pattern of SNCG in another study including 27 cases of esophageal cancer (ESC) demonstrated that it is downregulated in 16 out of 27 cases of ESC. Overexpression of SNCG in ESC 9706 cell line has shown that the ectopic expression of SNCG in ESC cell line inhibits cell growth in dish and colony formation in soft agar. Therefore, unlike breast and ovarian cancers, a reversed correlation between SNCG expression and ESC development was found, which led to a hypothesis that SNCG may play a role of a tumor suppressor in the development of human ESC.


Entity	Prostate cancer
Note	A strong association between SNCG expression and prostate cancer development is found. By performing genomic sequencing and methylation-specific PCR assays, an inclusive demethylation of CpG sites within the CpG island of SNCG gene in prostate cancer samples was established. These results suggest a loss of the epigenetic control of SNCG gene expression in tumors and demonstrate that the demethylation of SNCG CpG island is primarily responsible for the aberrant expression of SNCG in prostate cancerous tissues. A conclusion is drawn that that reactivation of SNCG gene expression by DNA demethylation is a common critical contributing factor to malignant progression of tumors and its expression in primary carcinomas is an effective molecular indicator of distant metastasis. Therefore, the methylation status of SNCG gene can be used as a sensitive molecular tool in early detections of tumorigenesis. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner.


Entity	Endometrial cancer
Note	SNCG expression is associated with poor outcome in endometrial adenocarcinoma. There is a positive association between SNCG expression and tumor grade, tumor stage, type II carcinomas, deep myometrial invasion and lymphovascular invasion. A correlation between SNCG and adverse outcomes, such as shorter overall survival and disease free survival is found. The expression level of SNCG in endometrioid endometrial carcinoma is closely associated with International Federation of Gynecology and Obstetrics (IFGO) stages, the depth of myometrial invasion and lymph nodes metastases (p<0.05). SNCG is considered a useful marker for endometrioid endometrial carcinoma invasion, metastasis and prognosis in endometrioid endometrial carcinoma.


Entity	Gallbladder cancer
Note	SNCG is highly expressed in human gallbladder cancer, and its abnormal expression is associated with tumor aggressiveness. SNCG gene silencing in NOZ cells inhibited cell growth, colony formation, and invasion. In addition, it directly increased the effectiveness of paclitaxel in inducing G2/M cell-cycle arrest and cell apoptosis. A decrease in tumor growth and weight was found in mice injected with SNCG-silenced NOZ cells. Together, these findings suggest that SNCG plays an important role in the progression of human gallbladder cancer.


Entity	Colon cancer
Note	Abnormal expression of SNCG protein has been demonstrated in colon cancer. SNCG predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen (CEA). SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival and overall survival (P < 0.0001). SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

Bibliography

Synucleins are expressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary.

Bruening W, Giasson BI, Klein-Szanto AJ, Lee VM, Trojanowski JQ, Godwin AK.

Cancer. 2000 May 1;88(9):2154-63.

PMID 10813729

Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression.

Chen J, Jiao L, Xu C, Yu Y, Zhang Z, Chang Z, Deng Z, Sun Y.

BMC Cancer. 2012 Dec 11;12:593. doi: 10.1186/1471-2407-12-593.

PMID 23231703

The role of CpG islands hypomethylation and abnormal expression of neuronal protein synuclein-gamma (SNCG) in ovarian cancer.

Czekierdowski A, Czekierdowska S, Wielgos M, Smolen A, Kaminski P, Kotarski J.

Neuro Endocrinol Lett. 2006 Jun;27(3):381-6.

PMID 16816827

gamma-Synuclein interacts with phospholipase Cbeta2 to modulate G protein activation.

Golebiewska U, Guo Y, Khalikaprasad N, Zurawsky C, Yerramilli VS, Scarlata S.

PLoS One. 2012;7(8):e41067. doi: 10.1371/journal.pone.0041067. Epub 2012 Aug 8.

PMID 22905097

Neuronal protein synuclein gamma predicts poor clinical outcome in breast cancer.

Guo J, Shou C, Meng L, Jiang B, Dong B, Yao L, Xie Y, Zhang J, Chen Y, Budman DR, Shi YE.

Int J Cancer. 2007 Sep 15;121(6):1296-305.

PMID 17534899

Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma.

Gupta A, Godwin AK, Vanderveer L, Lu A, Liu J.

Cancer Res. 2003 Feb 1;63(3):664-73.

PMID 12566312

Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1.

Gupta A, Inaba S, Wong OK, Fang G, Liu J.

Oncogene. 2003 Oct 23;22(48):7593-9.

PMID 14576821

SNCG gene silencing in gallbladder cancer cells inhibits key tumorigenic activities.

Han S, She F, Wang D, Yao X, Jiang L, Chen Y.

Front Biosci (Landmark Ed). 2012 Jan 1;17:1589-98.

PMID 22201822

Synuclein gamma inhibits the mitotic checkpoint function and promotes chromosomal instability of breast cancer cells.

Inaba S, Li C, Shi YE, Song DQ, Jiang JD, Liu J.

Breast Cancer Res Treat. 2005 Nov;94(1):25-35.

PMID 16142440

Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing.

Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G, Joseph BK, Rosen C, Shi YE.

Cancer Res. 1997 Feb 15;57(4):759-64.

PMID 9044857

Gamma synuclein, a novel heat-shock protein-associated chaperone, stimulates ligand-dependent estrogen receptor alpha signaling and mammary tumorigenesis.

Jiang Y, Liu YE, Goldberg ID, Shi YE.

Cancer Res. 2004 Jul 1;64(13):4539-46.

PMID 15231664

Absence of mutation in the beta- and gamma-synuclein genes in familial autosomal dominant Parkinson's disease.

Lavedan C, Buchholtz S, Auburger G, Albin RL, Athanassiadou A, Blancato J, Burguera JA, Ferrell RE, Kostic V, Leroy E, Leube B, Mota-Vieira L, Papapetropoulos T, Pericak-Vance MA, Pinkus J, Scott WK, Ulm G, Vasconcelos J, Vilchez JJ, Nussbaum RL, Polymeropoulos MH.

DNA Res. 1998 Dec 31;5(6):401-2.

PMID 10048491

Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen.

Liu C, Dong B, Lu A, Qu L, Xing X, Meng L, Wu J, Eric Shi Y, Shou C.

BMC Cancer. 2010 Jul 7;10:359. doi: 10.1186/1471-2407-10-359.

PMID 20604972

Elevated serum synuclein-gamma in patients with gastrointestinal and esophageal carcinomas.

Liu C, Ma H, Qu L, Wu J, Meng L, Shou C.

Hepatogastroenterology. 2012 Oct;59(119):2222-7.

PMID 22440249

Loss of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in a wide range of human cancers.

Liu H, Liu W, Wu Y, Zhou Y, Xue R, Luo C, Wang L, Zhao W, Jiang JD, Liu J.

Cancer Res. 2005 Sep 1;65(17):7635-43.

PMID 16140929

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamma in lung cancer cells by downregulation of DNMT3B.

Liu H, Zhou Y, Boggs SE, Belinsky SA, Liu J.

Oncogene. 2007 Aug 30;26(40):5900-10. Epub 2007 Mar 19.

PMID 17369845

Blockade of AP1 transactivation abrogates the abnormal expression of breast cancer-specific gene 1 in breast cancer cells.

Lu A, Zhang F, Gupta A, Liu J.

J Biol Chem. 2002 Aug 30;277(35):31364-72. Epub 2002 Jun 18.

PMID 12072430

Synuclein-gamma (SNCG) protein expression is associated with poor outcome in endometrial adenocarcinoma.

Mhawech-Fauceglia P, Wang D, Syriac S, Godoy H, Dupont N, Liu S, Odunsi K.

Gynecol Oncol. 2012 Jan;124(1):148-52. doi: 10.1016/j.ygyno.2011.09.037. Epub 2011 Oct 19.

PMID 22015044

gamma-synuclein is a novel player in the control of body lipid metabolism.

Millership S, Ninkina N, Rochford JJ, Buchman VL.

Adipocyte. 2013 Oct 1;2(4):276-80. doi: 10.4161/adip.25162. Epub 2013 May 28.

PMID 24052906

Contrasting effects of alpha-synuclein and gamma-synuclein on the phenotype of cysteine string protein alpha (CSPa) null mutant mice suggest distinct function of these proteins in neuronal synapses.

Ninkina N, Peters OM, Connor-Robson N, Lytkina O, Sharfeddin E, Buchman VL.

J Biol Chem. 2012 Dec 28;287(53):44471-7. doi: 10.1074/jbc.M112.422402. Epub 2012 Nov 5.

PMID 23129765

Organization, expression and polymorphism of the human persyn gene.

Ninkina NN, Alimova-Kost MV, Paterson JW, Delaney L, Cohen BB, Imreh S, Gnuchev NV, Davies AM, Buchman VL.

Hum Mol Genet. 1998 Sep;7(9):1417-24.

PMID 9700196

Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways.

Pan ZZ, Bruening W, Giasson BI, Lee VM, Godwin AK.

J Biol Chem. 2002 Sep 20;277(38):35050-60. Epub 2002 Jul 16.

PMID 12121974

Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis.

Peters OM, Millership S, Shelkovnikova TA, Soto I, Keeling L, Hann A, Marsh-Armstrong N, Buchman VL, Ninkina N.

Neurobiol Dis. 2012 Oct;48(1):124-31. doi: 10.1016/j.nbd.2012.06.016. Epub 2012 Jun 30.

PMID 22750530

Secondary structure and dynamics of micelle bound beta- and gamma-synuclein.

Sung YH, Eliezer D.

Protein Sci. 2006 May;15(5):1162-74. Epub 2006 Apr 5.

PMID 16597821

Cell-specific post-transcriptional regulation of gamma-synuclein gene by micro-RNAs.

Surgucheva I, Gunewardena S, Rao HS, Surguchov A.

PLoS One. 2013 Sep 11;8(9):e73786. doi: 10.1371/journal.pone.0073786. eCollection 2013.

PMID 24040069

Synoretin--A new protein belonging to the synuclein family.

Surguchov A, Surgucheva I, Solessio E, Baehr W.

Mol Cell Neurosci. 1999 Feb;13(2):95-103.

PMID 10192768

Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis.

Wu K, Quan Z, Weng Z, Li F, Zhang Y, Yao X, Chen Y, Budman D, Goldberg ID, Shi YE.

Breast Cancer Res Treat. 2007 Mar;101(3):259-67. Epub 2006 Jul 4.

PMID 16821081

Stage-specific expression of breast cancer-specific gene gamma-synuclein.

Wu K, Weng Z, Tao Q, Lin G, Wu X, Qian H, Zhang Y, Ding X, Jiang Y, Shi YE.

Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):920-5.

PMID 14504205

Demethylation of the synuclein gamma gene CpG island in primary gastric cancers and gastric cancer cell lines.

Yanagawa N, Tamura G, Honda T, Endoh M, Nishizuka S, Motoyama T.

Clin Cancer Res. 2004 Apr 1;10(7):2447-51.

PMID 15073123

Abnormal activation of the synuclein-gamma gene in hepatocellular carcinomas by epigenetic alteration.

Zhao W, Liu H, Liu W, Wu Y, Chen W, Jiang B, Zhou Y, Xue R, Luo C, Wang L, Jiang JD, Liu J.

Int J Oncol. 2006 May;28(5):1081-8.

PMID 16596223

Down-regulation of gamma-synuclein in human esophageal squamous cell carcinoma.

Zhou CQ, Liu S, Xue LY, Wang YH, Zhu HX, Lu N, Xu NZ.

World J Gastroenterol. 2003 Sep;9(9):1900-3.

PMID 12970872

Citation

This paper should be referenced as such :

A Surguchov

SNCG (synuclein, gamma (breast cancer-specific protein 1))

Atlas Genet Cytogenet Oncol Haematol. 2015;19(3):210-216.

Free journal version : [ pdf ] [ DOI ]

History of this paper:

Czekierdowski, A ; Czekierdowska, S. SNCG (synuclein, gamma (breast cancer-specific protein 1)). Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):12-16.

http://documents.irevues.inist.fr/bitstream/handle/2042/38465/06-2007-SNCGID42343ch10q23.pdf

External links

	Nomenclature
HGNC (Hugo)	SNCG 11141
	Cards
Atlas	SNCGID42343ch10q23
Entrez_Gene (NCBI)	SNCG synuclein gamma
Aliases	BCSG1; SR
GeneCards (Weizmann)	SNCG
Ensembl hg19 (Hinxton)	ENSG00000173267 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000173267 [Gene_View] ENSG00000173267 [Sequence] chr10:86958599-86963258 [Contig_View] SNCG [Vega]
ICGC DataPortal	ENSG00000173267
TCGA cBioPortal	SNCG
AceView (NCBI)	SNCG
Genatlas (Paris)	SNCG
SOURCE (Princeton)	SNCG
Genetics Home Reference (NIH)	SNCG
	Genomic and cartography
GoldenPath hg38 (UCSC)	SNCG - chr10:86958599-86963258 + 10q23.2 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	SNCG - 10q23.2 [Description] (hg19-Feb_2009)
GoldenPath	SNCG - 10q23.2 [CytoView hg19] SNCG - 10q23.2 [CytoView hg38]
ImmunoBase	ENSG00000173267
genome Data Viewer NCBI	SNCG [Mapview hg19]
OMIM	602998
	Gene and transcription
Genbank (Entrez)	AF010126 AF017256 AF411524 AK223367 AK312141
RefSeq transcript (Entrez)	NM_001330120 NM_003087
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	SNCG
Alternative Splicing Gallery	ENSG00000173267
Gene Expression	SNCG [ NCBI-GEO ] SNCG [ EBI - ARRAY_EXPRESS ] SNCG [ SEEK ] SNCG [ MEM ]
Gene Expression Viewer (FireBrowse)	SNCG [ Firebrowse - Broad ]
Genevisible	Expression of SNCG in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	6623
GTEX Portal (Tissue expression)	SNCG
Human Protein Atlas	ENSG00000173267-SNCG [pathology] [cell] [tissue]
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	O76070 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	O76070 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	O76070
Splice isoforms : SwissVar	O76070
PhosPhoSitePlus	O76070
Domains : Interpro (EBI)	Synuclein Synuclein_gamma
Domain families : Pfam (Sanger)	Synuclein (PF01387)
Domain families : Pfam (NCBI)	pfam01387
Conserved Domain (NCBI)	SNCG
Blocks (Seattle)	SNCG
Superfamily	O76070
Human Protein Atlas [tissue]	ENSG00000173267-SNCG [tissue]
Peptide Atlas	O76070
HPRD	04297
IPI	IPI00297714 IPI00883944 IPI00643394
	Protein Interaction databases
DIP (DOE-UCLA)	O76070
IntAct (EBI)	O76070
BioGRID	SNCG
STRING (EMBL)	SNCG
ZODIAC	SNCG
	Ontologies - Pathways
QuickGO	O76070
Ontology : AmiGO	protein binding cytoplasm centrosome spindle chemical synaptic transmission adult locomotory behavior protein secretion regulation of dopamine secretion nuclear body axon neuronal cell body synapse regulation of neurotransmitter secretion perinuclear region of cytoplasm synapse organization extracellular exosome
Ontology : EGO-EBI	protein binding cytoplasm centrosome spindle chemical synaptic transmission adult locomotory behavior protein secretion regulation of dopamine secretion nuclear body axon neuronal cell body synapse regulation of neurotransmitter secretion perinuclear region of cytoplasm synapse organization extracellular exosome
NDEx Network	SNCG
Atlas of Cancer Signalling Network	SNCG
Wikipedia pathways	SNCG
	Orthology - Evolution
OrthoDB	6623
GeneTree (enSembl)	ENSG00000173267
Phylogenetic Trees/Animal Genes : TreeFam	SNCG
HOGENOM	O76070
Homologs : HomoloGene	SNCG
Homology/Alignments : Family Browser (UCSC)	SNCG
	Gene fusions - Rearrangements
Fusion : Fusion_Hub	ADIRF--SNCG CDC25B--SNCG MMRN2--SNCG SNCG--ADIRF SNCG--ZNF785 TET1--SNCG
Fusion : Quiver	SNCG
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	SNCG [hg38]
dbVar	SNCG
ClinVar	SNCG
Monarch	SNCG
1000_Genomes	SNCG
Exome Variant Server	SNCG
GNOMAD Browser	ENSG00000173267
Varsome Browser	SNCG
Genomic Variants (DGV)	SNCG [DGVbeta]
DECIPHER	SNCG [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	SNCG
	Mutations
ICGC Data Portal	SNCG
TCGA Data Portal	SNCG
Broad Tumor Portal	SNCG
OASIS Portal	SNCG [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMIC	SNCG [overview] [genome browser] [tissue] [distribution]
Somatic Mutations in Cancer : COSMIC3D	SNCG
Mutations and Diseases : HGMD	SNCG
LOVD (Leiden Open Variation Database)	Whole genome datasets
LOVD (Leiden Open Variation Database)	LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)	LOVD 3.0 shared installation
BioMuta	search SNCG
DgiDB (Drug Gene Interaction Database)	SNCG
DoCM (Curated mutations)	SNCG (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	SNCG (select a term)
intoGen	SNCG
NCG6 (London)	select SNCG
Cancer3D	SNCG(select the gene name)
Impact of mutations	[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	602998
Orphanet
DisGeNET	SNCG
Medgen	SNCG
Genetic Testing Registry	SNCG
NextProt	O76070 [Medical]
GENETests	SNCG
Target Validation	SNCG
Huge Navigator	SNCG [HugePedia]
ClinGen	SNCG
	Clinical trials, drugs, therapy
MyCancerGenome	SNCG
Protein Interactions : CTD
Pharm GKB Gene	PA35989
Pharos	O76070
Clinical trial	SNCG
	Miscellaneous
canSAR (ICR)	SNCG (select the gene name)
Harmonizome	SNCG
DataMed Index	SNCG
	Probes
	Litterature
PubMed	114 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
EVEX	SNCG

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Fri Jan 1 19:01:49 CET 2021

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

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.