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Tbio Cell death activator CIDE-3

Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment. As mature adipocytes, that express high CIDEC levels, are quite resistant to apoptotic stimuli, the physiological significance of its role in apoptosis is unclear. May play a role in the modulation of the response to osmotic stress by preventing NFAT5 to translocate into the nucleus and activate its target genes expression.

This gene encodes a member of the cell death-inducing DNA fragmentation factor-like effector family. Members of this family play important roles in apoptosis. The encoded protein promotes lipid droplet formation in adipocytes and may mediate adipocyte apoptosis. This gene is regulated by insulin and its expression is positively correlated with insulin sensitivity. Mutations in this gene may contribute to insulin resistant diabetes. A pseudogene of this gene is located on the short arm of chromosome 3. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

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Property Summary

NCBI Gene PubMed Count 32
PubMed Score 69.05
PubTator Score 46.62

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Disease Target Count
Dermatitis, Allergic Contact 66
Disease Target Count P-value
psoriasis 6685 3.1e-10
ductal carcinoma in situ 1745 1.1e-04
invasive ductal carcinoma 2950 2.7e-04
breast carcinoma 1614 3.1e-03
Atopic dermatitis 944 1.5e-02
fibroadenoma 557 2.0e-02
Disease Target Count
Lipodystrophy, familial partial, 5 1

Expression

  Differential Expression (6)

Disease log2 FC p
Atopic dermatitis -1.400 1.5e-02
breast carcinoma -2.500 3.1e-03
fibroadenoma -3.400 2.0e-02
psoriasis -1.500 3.1e-10
ductal carcinoma in situ -4.100 1.1e-04
invasive ductal carcinoma -4.400 2.7e-04

Synonym

Accession Q96AQ7 C9JMN7 Q67DW9 Q9GZY9
Symbols CIDE3
FPLD5
FSP27
CIDE-3

Gene

CIDEC

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (11)

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 GO Component (4)

 GO Process (6)

 Compartment GO Term (18)

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 IMPC Phenotype (14)

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 MGI Phenotype (7)

 HCA RNA Cell Line (32)

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Pathway (5)

Protein-protein Interaction (2)

TOP1   PRSS2  

Gene RIF (20)

PMID Text
26367078 data suggested that Cidec could interact with and down-regulate AMPKalpha through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation
26099526 Hepatic expression of FSP27/CIDEC is highly up-regulated in in patients with alcoholic steatohepatitis and this up-regulation contributes to alcohol-induced liver damage.
25210844 It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-gamma, increases its expression, and decreases lipolysis.
24742676 Data indicate that fat-specific protein 27 (FSP27) increases the inhibitory effect of transcription factor Egr1 on the adipose triglyceride lipase (ATGL) promoter.
24627478 results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes
24126816 After bariatric surgery-induced weight loss, CIDEC/FSP27 gene/protein expression in SAT increased significantly. Findings suggest a positive functional interaction between CIDEC/FSP27 & mitochondrial biogenesis-related genes in human adipose tissue
24025675 homo-dimeric structure of the CIDE-N domain of FSP27 will provide important information that will enable better understanding of the function of FSP27.
23475172 CIDE proteins expression correlate with tumor and survival characteristics in patients with renal cell carcinoma.
23233732 The results suggest that FSP27 not only modulates LD homeostasis but also modulates the response to osmotic stress via a physical interaction with NFAT5 at the LD surface.
23220584 Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.
21865223 Results demonstrated that CIDEC-induced apoptosis was independent of FADD, suggesting that CIDEC-induced apoptosis might be in a death-receptor-independent, caspase-8-dependent manner.
21636835 Insulin regulates CIDEA and CIDEC expression via PI3K, and it regulates expression of each protein via Akt1/2-and JNK2-dependent pathways, respectively, in human adipocytes.
20957525 The expression of CIDE-3 was decreased in hepatocellular carcinoma (HCC) tissue, compared to adjacent normal tissues, and CIDE-3 expression and HCC differentiation were positively correlated.
20154362 These results suggest that CIDEA and CIDEC are novel genes regulated by insulin in human adipocytes and may play key roles in the effects of insulin, such as anti-apoptosis and lipid droplet formation.
20089860 Fat-specific protein 27 undergoes ubiquitin-dependent degradation regulated by triacylglycerol synthesis and lipid droplet formation
20049731 CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human.
19661960 Following gastric bypass the hepatic expression of CIDEC is downregulated by marked weight loss.
18702959 CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
18334488 FSP27 binds to lipid droplets and regulates their enlargement
12429024 cloning and characterization as a member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family

AA Sequence 

MEYAMKSLSLLYPKSLSRHVSVRTSVVTQQLLSEPSPKAPRARPCRVSTADRSVRKGIMAYSLEDLLLKV      1 - 70
RDTLMLADKPFFLVLEEDGTTVETEEYFQALAGDTVFMVLQKGQKWQPPSEQGTRHPLSLSHKPAKKIDV     71 - 140
ARVTFDLYKLNPQDFIGCLNVKATFYDTYSLSYDLHCCGAKRIMKEAFRWALFSMQATGHVLLGTSCYLQ    141 - 210
QLLDATEEGQPPKGKASSLIPTCLKILQ                                              211 - 238
//

Text Mined References (34)

PMID Year Title
26367078 2015 Cidec promotes the differentiation of human adipocytes by degradation of AMPK? through ubiquitin-proteasome pathway.
26099526 2015 Fat-Specific Protein 27/CIDEC Promotes Development of Alcoholic Steatohepatitis in Mice and Humans.
25210844 2014 Effects of pioglitazone mediated activation of PPAR-? on CIDEC and obesity related changes in mice.
24742676 2014 Fat-specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of transcription factor Egr1 on transcription of adipose triglyceride lipase.
24627478 2014 Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.
24126816 2014 CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in human adipose tissue, both increasing after weight loss.
24025675 2013 Molecular basis for homo-dimerization of the CIDE domain revealed by the crystal structure of the CIDE-N domain of FSP27.
23475172 2013 Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance.
23399566 2013 FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes.
23233732 2013 Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress.
23220584 2013 Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.
21865223 2011 Human cell-death-inducing DFF45-like effector C induces apoptosis via caspase-8.
21636835 2011 Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes.
20967381 2011 Which CIDE are you on? Apoptosis and energy metabolism.
20945533 2010 Cell death-inducing DFF45-like effector, a lipid droplet-associated protein, might be involved in the differentiation of human adipocytes.
20440297 2010 Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression.
20154362 2010 Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes.
20049731 2009 Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.
19843876 2009 Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.
19661960 2010 Hepatic expression of cell death-inducing DFFA-like effector C in obese subjects is reduced by marked weight loss.
19276890 2009 CIDE proteins and metabolic disorders.
18702959 2008 Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
18509062 2008 Cidea is associated with lipid droplets and insulin sensitivity in humans.
18500987 2008 Molecular evolution of Cide family proteins: novel domain formation in early vertebrates and the subsequent divergence.
18334488 2008 Fat-specific protein 27 regulates storage of triacylglycerol.
18171433 2008 RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
16507259 2006 [Construction of the prokaryotic expression vector and expression of human CIDE-3 gene].
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12429024 2003 Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family.