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Information on EC 2.7.11.8 - Fas-activated serine/threonine kinase
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2.7.11.8 Fas-activated serine/threonine kinaseIUBMB Comments
This enzyme is activated during Fas-mediated apoptosis. Following Fas ligation, the enzyme, which is constitutively phosphorylated, is dephosphorylated, and it is the dephosphorylated form that causes phosphorylation of TIA-1, a nuclear RNA-binding protein. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation.
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Word Map
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
fastk, fast k, fas-activated serine/threonine kinase, fas-activated serine/threonine phosphoprotein, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 2.7.1.37
-
-
formerly, part transferred
-
Fas-activated serine/threonine kinase
FASTK
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + [Fas-activated serine/threonine protein] = ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP:[Fas-activated serine/threonine protein] phosphotransferase
This enzyme is activated during Fas-mediated apoptosis. Following Fas ligation, the enzyme, which is constitutively phosphorylated, is dephosphorylated, and it is the dephosphorylated form that causes phosphorylation of TIA-1, a nuclear RNA-binding protein. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation.
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CAS REGISTRY NUMBER
COMMENTARY
170347-50-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Fas-activated serine/threonine protein
ADP + Fas-activated serine/threonine phosphoprotein
-
-
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
ATP + [T-cell intracellular antigen 1]
ADP + [T-cell intracellular antigen 1 phosphoprotein]
ATP + TIA-1
ADP + ?
rapidly activated during Fas-mediated apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program
-
-
?
ATP + TIA-1
ADP + phosphorylated TIA-1
FAST serves as a sensor for mitochondrial stress modulating a TIA-1 regulated posttranscriptional stress response program, FAST might prevent TIA-1 mediated silencing of mRNA encoding inhibitors of of apoptosis
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
?
ATP + [T-cell intracellular antigen 1]
ADP + [T-cell intracellular antigen 1 phosphoprotein]
-
FAST K is known to interact with and phosphorylate TIA-1, effects of FAST K on other splicing factors and associated splicing regulatory motifs are mediated by changes in the function of TIA-1/TIAR, i.e. T-cell intracellular antigen 1 and TIA-related proteins, interaction analysis of FAST K with TIA, overview
-
-
?
ATP + [T-cell intracellular antigen 1]
ADP + [T-cell intracellular antigen 1 phosphoprotein]
-
in vitro phosphorylation of TIA-1 by FAST K results in enhanced U1 snRNP recruitment, overview
-
-
?
additional information
?
-
FAST serves as a sensor for mitochondrial stress modulating a TIA-1 regulated posttranscriptional stress response program, FAST is a survival protein, modulating the NF-kappaB-dependent survival pathway, and has antiapoptotic effects inhibiting Fas-and UV-induced apoptosis, involving activation of caspase-3, its antiapoptotic effects are inhibited by TIA-1, FAST might prevent TIA-1 mediated silencing of mRNA encoding inhibitors of of apoptosis
-
-
?
additional information
?
-
the interaction of the enzyme with protein BCL-XL is involved in regulation of mitochondrial metabolism during Fas-induced apoptosis
-
-
?
additional information
?
-
the enzyme interacts with BCL-XL at the outer mitochondrial membrane
-
-
?
additional information
?
-
the enzyme interacts with BCL-XL requiring the BCL-2-homology-3 (BH3)-related domain and the MTD domain of BCL-XL
-
-
?
additional information
?
-
-
Fas signaling is connected with the activity of splicing factors that modulate Fas alternative splicing, suggesting the existence of an autoregulatory loop that could serve to amplify Fas responses, overview
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + TIA-1
ADP + ?
rapidly activated during Fas-mediated apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program
-
-
?
ATP + TIA-1
ADP + phosphorylated TIA-1
FAST serves as a sensor for mitochondrial stress modulating a TIA-1 regulated posttranscriptional stress response program, FAST might prevent TIA-1 mediated silencing of mRNA encoding inhibitors of of apoptosis
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
ATP + [T-cell intracellular antigen 1]
ADP + [T-cell intracellular antigen 1 phosphoprotein]
-
FAST K is known to interact with and phosphorylate TIA-1, effects of FAST K on other splicing factors and associated splicing regulatory motifs are mediated by changes in the function of TIA-1/TIAR, i.e. T-cell intracellular antigen 1 and TIA-related proteins, interaction analysis of FAST K with TIA, overview
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
?
ATP + [Fas-activated serine/threonine protein]
ADP + [Fas-activated serine/threonine phosphoprotein]
-
-
-
?
additional information
?
-
FAST serves as a sensor for mitochondrial stress modulating a TIA-1 regulated posttranscriptional stress response program, FAST is a survival protein, modulating the NF-kappaB-dependent survival pathway, and has antiapoptotic effects inhibiting Fas-and UV-induced apoptosis, involving activation of caspase-3, its antiapoptotic effects are inhibited by TIA-1, FAST might prevent TIA-1 mediated silencing of mRNA encoding inhibitors of of apoptosis
-
-
?
additional information
?
-
the interaction of the enzyme with protein BCL-XL is involved in regulation of mitochondrial metabolism during Fas-induced apoptosis
-
-
?
additional information
?
-
-
Fas signaling is connected with the activity of splicing factors that modulate Fas alternative splicing, suggesting the existence of an autoregulatory loop that could serve to amplify Fas responses, overview
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-3-(3,4-dimethoxyphenyl)-1-[4-[(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-en-1-one
-
(2E)-3-(4-chlorophenyl)-1-[4-[(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-en-1-one
-
(2E)-3-phenyl-1-[4-[(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-en-1-one
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Astrocytoma
miR-106a-5p Inhibits the Proliferation and Migration of Astrocytoma Cells and Promotes Apoptosis by Targeting FASTK.
Breast Neoplasms
Thienopyrimidine-Chalcone Hybrid Molecules Inhibit Fas-Activated Serine/Threonine Kinase: An Approach To Ameliorate Antiproliferation in Human Breast Cancer Cells.
Carcinoma
Effects of marine sponge extracts on mitogen-activated protein kinase (MAPK/ERK(1,2)) activity in SW-13 human adrenal carcinoma cells.
Carcinoma, Ehrlich Tumor
Effect of protein kinase inhibitors on activity of mammalian small heat-shock protein (HSP25) kinase.
Cardiomyopathies
Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy.
Cardiomyopathy, Alcoholic
Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy.
fas-activated serine/threonine kinase deficiency
Genetic ablation of fas-activated serine/threonine kinase ameliorates alcoholic liver disease through modulating HuR-SIRT1 mRNA complex stability.
Glioma
Protein kinase translocation following beta-adrenergic receptor activation in C6 glioma cells.
Glucose Intolerance
Genetic ablation of Fas-activated serine/threonine kinase ameliorates obesity-related hepatic glucose and lipid metabolic disorders via sirtuin-1 signaling.
Heart Failure
Myocardial gene expression of matched hibernating and control tissue from patients with ischemic left ventricular dysfunction.
Infections
In vivo and in vitro phosphorylation of DNA-dependent RNA polymerase of Escherichia coli by bacteriophage-T7-induced protein kinase.
Insulin Resistance
Genetic ablation of Fas-activated serine/threonine kinase ameliorates obesity-related hepatic glucose and lipid metabolic disorders via sirtuin-1 signaling.
Liver Diseases, Alcoholic
Genetic ablation of fas-activated serine/threonine kinase ameliorates alcoholic liver disease through modulating HuR-SIRT1 mRNA complex stability.
Lymphoma
Altered regulation of cyclic AMP-dependent protein kinase in a mouse lymphoma cell line.
Lymphoma
Subunit interaction in cyclic AMP-dependent protein kinase of mutant lymphoma cells.
Metabolic Diseases
Genetic ablation of Fas-activated serine/threonine kinase ameliorates obesity-related hepatic glucose and lipid metabolic disorders via sirtuin-1 signaling.
Mitochondrial Diseases
FASTKD1 and FASTKD4 have opposite effects on expression of specific mitochondrial RNAs, depending upon their endonuclease-like RAP domain.
Mitochondrial Encephalomyopathies
FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation.
Myocardial Infarction
Fas-Activated Serine/Threonine Kinase Governs Cardiac Mitochondrial Complex I Functional Integrity in Ischemia/Reperfusion Heart.
Neoplasms
Characterization of protein tyrosine kinase activity in murine Leydig tumor cells.
Neoplasms
Effect of protein kinase inhibitors on activity of mammalian small heat-shock protein (HSP25) kinase.
Neoplasms
miR-106a-5p Inhibits the Proliferation and Migration of Astrocytoma Cells and Promotes Apoptosis by Targeting FASTK.
Neoplasms
Thienopyrimidine-Chalcone Hybrid Molecules Inhibit Fas-Activated Serine/Threonine Kinase: An Approach To Ameliorate Antiproliferation in Human Breast Cancer Cells.
Neuroblastoma
Participation of type II protein kinase A in the retinoic acid-induced growth inhibition of SH-SY5Y human neuroblastoma cells.
Neuroblastoma
Phosphorylation of endogenous proteins by adenosine 3':5'-monophosphate-dependent protein kinase in mouse neuroblastoma cells.
Plasmacytoma
Resolution and general properties of different types of ribosomal protein kinases in mouse plasmocytoma.
Pneumonia
Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation.
Sarcoma
Viral src gene products are related to the catalytic chain of mammalian cAMP-dependent protein kinase.
Sarcoma, Avian
Cytosolic malic dehydrogenase activity is associated with a putative substrate for the transforming gene product of Rous sarcoma virus.
Sarcoma, Avian
Protein kinase and its regulatory effect on reverse transcriptase activity of Rous sarcoma virus.
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00015
(2E)-3-(3,4-dimethoxyphenyl)-1-[4-[(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-en-1-one
Homo sapiens
pH 8.0, 25°C, IC50 for MCF-7 cells: 0.0082 mM
0.00017
(2E)-3-(4-chlorophenyl)-1-[4-[(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-en-1-one
Homo sapiens
pH 8.0, 25°C, IC50 for MCF-7 cells: 0.00652 mM
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme has a mitochondrial targeting domain
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
malfunction
physiological function
drug target
FASTK is an important protein with its valuable implications in various diseases as it serves as a potential drug target
drug target
inhibitors of Fas-activated serine/threonine kinase may be exploited as potential anticancer agents
drug target
restoration of FASTK expression through genetic approaches might be a promising therapeutic strategy for alcoholic cardiomyopathy (ACM)
malfunction
ablating enzyme expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo
malfunction
compared to wild type control, alcohol-related myocardial morphological (hypertrophy, fibrosis and cardiomyocyte apoptosis) and functional (reduced ejection fraction and compromised cardiomyocyte contraction) anomalies are worsened in FASTK deficient mice
malfunction
macrophages from FASTK-/- mice exhibit a marked increase in nonopsonic phagocytosis of bacteria. Activity of mitochondrial respiratory complex I is specifically reduced by almost 50% in FASTK-/- macrophages
physiological function
the mitochondrial isoform is essential for ND6 mRNA biogenesis and complex I activity
physiological function
the enzyme (FASTK) is a mitochondria-associated nuclear protein that inhibits Fas- and UV-induced apoptosis
physiological function
the enzyme (FASTK) is implicated in the apoptotic evasion and, hence, the development of cancer
physiological function
the enzyme is a key post-transcriptional regulator of mitochondrial gene expression. Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy
physiological function
the mitochondrial isoform of FASTK modulates nonopsonic phagocytosis of bacteria by macrophages via regulation of respiratory complex I
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FASTK_HUMAN
549
0
61104
Swiss-Prot
other Location (Reliability: 5)
FASTK_MOUSE
511
0
57726
Swiss-Prot
Mitochondrion (Reliability: 5)
B7Q583_IXOSC
602
0
68113
TrEMBL
other Location (Reliability: 1)
A0A8M1NSV6_DANRE
914
0
101617
TrEMBL
Mitochondrion (Reliability: 1)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
enzyme is phosphorylated on serine and threonine residues. In response to Fas ligation, it is rapidly dephosphorylated and concomitantly activated to phosphorylate TIA-1
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
urea
the folding/unfolding transitions of urea-induced denaturation is monitored with the help of circular dichroism, intrinsic fluorescence, and UV absorption spectroscopies. Analysis of transition curves obtained from different probes reveal a coincidence of denaturation curves, suggesting that folding/unfolding of FASTK follows a two-state process with the midpoint (Cm) value at 3.50 M. Urea-induced denaturation curves are further analyzed to estimate change in the Gibbs free energy in the absence of urea (DGD0) associated with the equilibrium of denaturation. To get atomistic insights into the urea-induced denaturation of FASTK, an all-atom molecular dynamics simulation for 100 ns is performed
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
HA-tagged FAST K overexpression in HeLa cells enhances exon 6 inclusion of Fas reporters transfected in the cells, effects of FAST K are mediated by changes in the function of TIA-1/TIAR, i.e. T-cell intracellular antigen 1, and TIA-related proteins, the effects of FAST K overexpression are largely suppressed by depletion of TIA-1 and TIAR and are significantly compromised by mutation of a TIA-1/TIAR-responsive enhancer present downstream of exon 6 5' splice site, expression of GST-tagged TIA in HeLa cells
-
kinase domain of FASTK353-444 is cloned in pET28a, and the recombinant FASTK is expressed in Escherichia coli BL21 (DE3) cells
overexpression of HA-tagged enzyme in HeLa cells and in COS-7 cells, expression of GFP-tagged enzyme in COS-7 cells
overexpression of HA-tagged enzyme in HeLa cells and in COS-7 cells, recombinant FAST promotes the expression of co-transfected reporter proteins, e.g. beta-galactosidase, via its TIA-1 binding domain, and increases the expression of endogenous cIAP-1 and XIAP, but not GAPDH, in HeLa cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
miR-106a-5p upregulates enzyme expression via a post-transcriptional mechanism and by affecting its mRNA stability
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
the folding/unfolding transitions of urea-induced denaturation is monitored with the help of circular dichroism, intrinsic fluorescence, and UV absorption spectroscopies
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
the increased enzyme expression of is significantly associated with poor survival outcome in astrocytoma patients
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tian, Q.; Taupin, J.; Elledge, S.; Robertson, M.; Anderson, P.
Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis
J. Exp. Med.
182
865-874
1995
Homo sapiens (Q14296)
brenda
Li, W.; Kedersha, N.; Chen, S.; Gilks, N.; Lee, G.; Anderson, P.
FAST is a BCL-XL-associated mitochondrial protein
Biochem. Biophys. Res. Commun.
318
95-102
2004
Homo sapiens (Q14296)
brenda
Li, W.; Simarro, M.; Kedersha, N.; Anderson, P.
FAST is a survival protein that senses mitochondrial stress and modulates TIA-1-regulated changes in protein expression
Mol. Cell. Biol.
24
10178-10732
2004
Homo sapiens (Q14296)
brenda
Izquierdo, J.M.; Valcarcel, J.
Fas-activated serine/threonine kinase (FAST K) synergizes with TIA-1/TIAR proteins to regulate Fas alternative splicing
J. Biol. Chem.
282
1539-1543
2007
Homo sapiens
brenda
Jourdain, A.A.; Koppen, M.; Rodley, C.D.; Maundrell, K.; Gueguen, N.; Reynier, P.; Guaras, A.M.; Enriquez, J.A.; Anderson, P.; Simarro, M.; Martinou, J.C.
A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function
Cell Rep.
10
1110-1121
2015
Mus musculus, Mus musculus (Q9JIX9)
brenda
Zhi, F.; Zhou, G.; Shao, N.; Xia, X.; Shi, Y.; Wang, Q.; Zhang, Y.; Wang, R.; Xue, L.; Wang, S.; Wu, S.; Peng, Y.; Yang, Y.
miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK
PLoS ONE
8
e72390
2013
Homo sapiens
brenda
Amin, S.A.; Ghosh, K.; Gayen, S.; Jha, T.
Chemical-informatics approach to COVID-19 drug discovery Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease (PLpro) inhibitors
J. Biomol. Struct. Dyn.
2020
1-10
2020
Homo sapiens (Q14296)
brenda
Garcia Del Rio, A.; Delmiro, A.; Martin, M.A.; Cantalapiedra, R.; Carretero, R.; Durantez, C.; Menegotto, F.; Moran, M.; Serrano-Lorenzo, P.; De la Fuente, M.A.; Orduna, A.; Simarro, M.
The mitochondrial isoform of FASTK modulates nonopsonic phagocytosis of bacteria by macrophages via regulation of respiratory complex I
J. Immunol.
201
2977-2985
2018
Mus musculus (Q8C725)
brenda
Khan, N.S.; Khan, P.; Ansari, M.F.; Srivastava, S.; Hasan, G.M.; Husain, M.; Hassan, M.I.
Thienopyrimidine-chalcone hybrid molecules inhibit Fas-activated serine/threonine kinase an approach to ameliorate antiproliferation in human breast cancer cells
Mol. Pharm.
15
4173-4189
2018
Homo sapiens (Q14296), Homo sapiens
brenda
Zhang, F.; Wang, K.; Zhang, S.; Li, J.; Fan, R.; Chen, X.; Pei, J.
Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy
Redox Biol.
38
101778
2020
Mus musculus (Q9JIX9)
brenda
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