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Tbio RelA-associated inhibitor

Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis.

IASPP is one of the most evolutionarily conserved inhibitors of p53 (TP53; MIM 191170), whereas ASPP1 (MIM 606455) and ASPP2 (MIM 602143) are activators of p53.[supplied by OMIM, Mar 2008]

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Property Summary

NCBI Gene PubMed Count 83
PubMed Score 55.12
PubTator Score 67.39

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Sources (3)

Disease Target Count
Leukemia 88
Disease Target Count P-value
malignant mesothelioma 3163 2.04976227791013E-8
pituitary cancer 1972 5.69376468264155E-7
posterior fossa group A ependymoma 1511 4.3623547756573E-6
interstitial cystitis 2299 8.81757766051132E-5
colon cancer 1475 0.00292780097469403
aldosterone-producing adenoma 664 0.00895842042076255
active ulcerative colitis 477 0.0115366753971105
pancreatic ductal adenocarcinoma liver metastasis 1795 0.0121916821510703
cutaneous lupus erythematosus 1056 0.0135933147145994
esophageal adenocarcinoma 737 0.0295044626410749
spina bifida 1064 0.0333845847088694
Disease Target Count Z-score Confidence
Cancer 2346 3.52 1.8

Expression

  Differential Expression (11)

Disease log2 FC p
malignant mesothelioma 2.500 0.000
esophageal adenocarcinoma -1.500 0.030
cutaneous lupus erythematosus -1.400 0.014
pancreatic ductal adenocarcinoma liver m... 1.216 0.012
colon cancer 1.100 0.003
active ulcerative colitis 1.028 0.012
interstitial cystitis -1.900 0.000
posterior fossa group A ependymoma 1.200 0.000
aldosterone-producing adenoma -1.040 0.009
spina bifida -2.020 0.033
pituitary cancer -1.100 0.000

Synonym

Accession Q8WUF5 Q2PNZ9 Q5DU71 Q5I1X4 Q6P1R7 Q6PKF8 Q9Y290
Symbols RAI
RAI4
IASPP
NKIP1

Gene

PPP1R13L

PDB

2VGE  

  Ortholog (10)

Species Source
Chimp OMA EggNOG
Mouse OMA EggNOG Inparanoid
Rat OMA EggNOG Inparanoid
Dog OMA EggNOG Inparanoid
Horse OMA EggNOG
Cow OMA EggNOG Inparanoid
Opossum OMA EggNOG Inparanoid
Anole lizard OMA EggNOG Inparanoid
Xenopus OMA EggNOG Inparanoid
Zebrafish OMA EggNOG Inparanoid

 GO Function (4)

 GO Component (6)

 GO Process (13)

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 Compartment GO Term (28)

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 MGI Term (10)

 HCA RNA Cell Line (56)

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Pathway (9)

 UniProt Keyword (15)

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Gene RIF (69)

PMID Text
27075368 one novel region within PPP1R13L is hypomethylated in all transient neonatal diabetes type 1 patients included in this study
26787707 inhibitor of apoptosis-stimulating protein of p53 (iASPP) was identified to be a direct target of miR-140 in pancreatic duct adenocarcinoma specimens and cell lines
26646590 we show that iASPP is a novel substrate of caspases in response to apoptotic stimuli
26109723 One of the proteins identified, iASPP, showed reduced levels in the presence of GSK-3. Further, blocking iASPP activity increased cell death, particularly in p53 wild-type BC3 PEL cells.
25917613 results suggest that NFKB1 common variants and smoking duration and smoking duration-PPP1R13L rs1970764 interaction could be concerned with the lung cancer development in a Chinese population
25691752 These data demonstrate that by interacting with desmoplakin and desmin, iASPP is an important regulator of desmosomal function both in vitro and in vivo.
25675294 destabilization of p300/CBP by downregulation of iASPP expression levels appears to represent a molecular mechanism that contributes to chemoresistance in melanoma cells.
25341046 iASPP expression may act as a predictive marker of prostate cancer progression.
25149434 The present study showed that iASPP is overexpressed in oral cavity squamous cell carcinomas (OSCC)tissues and increased cytoplasmic iASPP is correlated with recurrence and poor survival outcomes in OSCC patients
24997996 data highlight the importance of 14-3-3 proteins in antiviral responses and identify RelA-associated inhibitor and sirtuin 1 as novel regulators of antiviral innate immune responses.
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AA Sequence 

MDSEAFQSARDFLDMNFQSLAMKHMDLKQMELDTAAAKVDELTKQLESLWSDSPAPPGPQAGPPSRPPRY      1 - 70
SSSSIPEPFGSRGSPRKAATDGADTPFGRSESAPTLHPYSPLSPKGRPSSPRTPLYLQPDAYGSLDRATS     71 - 140
PRPRAFDGAGSSLGRAPSPRPGPGPLRQQGPPTPFDFLGRAGSPRGSPLAEGPQAFFPERGPSPRPPATA    141 - 210
YDAPASAFGSSLLGSGGSAFAPPLRAQDDLTLRRRPPKAWNESDLDVAYEKKPSQTASYERLDVFARPAS    211 - 280
PSLQLLPWRESSLDGLGGTGKDNLTSATLPRNYKVSPLASDRRSDAGSYRRSLGSAGPSGTLPRSWQPVS    281 - 350
RIPMPPSSPQPRGAPRQRPIPLSMIFKLQNAFWEHGASRAMLPGSPLFTRAPPPKLQPQPQPQPQPQSQP    351 - 420
QPQLPPQPQTQPQTPTPAPQHPQQTWPPVNEGPPKPPTELEPEPEIEGLLTPVLEAGDVDEGPVARPLSP    421 - 490
TRLQPALPPEAQSVPELEEVARVLAEIPRPLKRRGSMEQAPAVALPPTHKKQYQQIISRLFHRHGGPGPG    491 - 560
GPEPELSPITEGSEARAGPPAPAPPAPIPPPAPSQSSPPEQPQSMEMRSVLRKAGSPRKARRARLNPLVL    561 - 630
LLDAALTGELEVVQQAVKEMNDPSQPNEEGITALHNAICGANYSIVDFLITAGANVNSPDSHGWTPLHCA    631 - 700
ASCNDTVICMALVQHGAAIFATTLSDGATAFEKCDPYREGYADCATYLADVEQSMGLMNSGAVYALWDYS    701 - 770
AEFGDELSFREGESVTVLRRDGPEETDWWWAALHGQEGYVPRNYFGLFPRVKPQRSKV                771 - 828
//

Text Mined References (92)

PMID Year Title
27173435 2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
27075368 2016 Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57.
26787707 2016 MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP.
26646590 2015 Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-?B.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
26109723 2015 A Screen for Extracellular Signal-Regulated Kinase-Primed Glycogen Synthase Kinase 3 Substrates Identifies the p53 Inhibitor iASPP.
25917613 2015 NFKB1 common variants and PPP1R13L and CD3EAP in relation to lung cancer risk in a Chinese population.
25691752 2015 iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.
25675294 2015 A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
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