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Tbio Nucleolar protein 3

Isoform 2: Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors (PubMed:15004034). Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:15509781). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (By similarity). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). Inhibits too myoblast differentiation through caspase inhibition (By similarity).

This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

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Property Summary

NCBI Gene PubMed Count 38
PubMed Score 180.73
PubTator Score 43.24

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Sources (3)

Disease Target Count P-value
atypical teratoid/rhabdoid tumor 1095 2.52154271099307E-4
astrocytic glioma 2241 0.00975295230778655
cutaneous lupus erythematosus 1056 0.0155537634595122
esophageal adenocarcinoma 737 0.0176010007179145
primary Sjogren syndrome 789 0.0273567815871881
ependymoma 2514 0.028328140796308
subependymal giant cell astrocytoma 2287 0.0301872698568252
Disease Target Count
Familial cortical myoclonus 1

Expression

  Differential Expression (7)

Disease log2 FC p
astrocytic glioma -1.200 0.010
ependymoma -1.100 0.028
esophageal adenocarcinoma -1.300 0.018
cutaneous lupus erythematosus -1.300 0.016
atypical teratoid/rhabdoid tumor -1.600 0.000
primary Sjogren syndrome -1.100 0.027
subependymal giant cell astrocytoma 1.218 0.030

Synonym

Accession O60936 B4DFL0 O60937
Symbols ARC
FCM
MYP
NOP
NOP30

Gene

NOL3

PDB

4UZ0  

  Ortholog (4)

Species Source
Mouse OMA EggNOG
Rat OMA EggNOG Inparanoid
Dog OMA EggNOG
Cow OMA EggNOG Inparanoid

 GO Function (4)

 GO Component (6)

 GO Process (21)

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 Compartment GO Term (29)

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 MGI Term (5)

 HCA RNA Cell Line (56)

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Pathway (1)

 UniProt Keyword (19)

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Gene RIF (30)

PMID Text
26721253 Increased ARC expression is associated with liver metastasis of colorectal cancer.
25079338 ARC is regulated via BIRC2/MAP3K14 signalling and its overexpression in AML or MSCs can function as a resistant factor to birinapant-induced leukaemia cell death.
24763054 RUNX3, miR-185 and ARC regulate the sensitivity of gastric cancer cells to chemotherapy.
23877130 high expression of ARC plays an important role in the pathogenesis of nasopharyngeal carcinoma and leads to X-radiation and cisplatin resistance in nasopharyngeal carcinoma.
22933109 ARC is a previously unrecognized inhibitor of apoptosis in beta-cells and that its protective effects are mediated through suppression of the ER stress response pathway.
22926851 This study utilized unbiased, genome-wide approaches to identify a NOL3 mutation that likely causes Familial cortical myoclonus.
22475487 HIF-1alpha directly bound to hypoxia-responsive element located at -419 to -414 of ARC gene, which is essential for HIF-1-induced expression.
22082675 ARC, previously unlinked to pulmonary hypertension, is a critical determinant of vascular remodeling in this syndrome.
22037876 Data show that ARC promotes breast carcinogenesis by driving primary tumor growth, invasion, and metastasis as well as by promoting chemoresistance in invasive cells.
21603976 (9)-THC for 24 h produces a dose-dependent NOP receptor down-regulation & decrease in NOP mRNA levels.
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AA Sequence 

MGNAQERPSETIDRERKRLVETLQADSGLLLDALLARGVLTGPEYEALDALPDAERRVRRLLLLVQGKGE      1 - 70
AACQELLRCAQRTAGAPDPAWDWQHVGPGYRDRSYDPPCPGHWTPEAPGSGTTCPGLPRASDPDEAGGPE     71 - 140
GSEAVQSGTPEEPEPELEAEASKEAEPEPEPEPELEPEAEAEPEPELEPEPDPEPEPDFEERDESEDS      141 - 208
//

Text Mined References (42)

PMID Year Title
26721253 2016 Expression of the apoptosis repressor with caspase recruitment domain (ARC) in liver metastasis of colorectal cancer and its correlation with DNA mismatch repair proteins and p53.
25255805 2014 Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.
25138476 2014 Screening of mutations in NOL3 in a myoclonic syndromes series.
25079338 2014 Apoptosis repressor with caspase recruitment domain modulates second mitochondrial-derived activator of caspases mimetic-induced cell death through BIRC2/MAP3K14 signalling in acute myeloid leukaemia.
24763054 2014 MicroRNA-185 regulates chemotherapeutic sensitivity in gastric cancer by targeting apoptosis repressor with caspase recruitment domain.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23877130 2013 ARC is highly expressed in nasopharyngeal carcinoma and confers X-radiation and cisplatin resistance.
22933109 2013 The apoptosis inhibitor ARC alleviates the ER stress response to promote ?-cell survival.
22926851 2012 Familial cortical myoclonus with a mutation in NOL3.
22475487 2012 Hypoxia-inducible factor 1 regulated ARC expression mediated hypoxia induced inactivation of the intrinsic death pathway in p53 deficient human colon cancer cells.
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