General Information:

Id: 6,387
Diseases: Metabolic
Mammalia
review
Reference: Cetrullo S et al.(2015) mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management Crit. Rev. Eukaryot. Gene Expr. 25: 59-75 [PMID: 25955819]

Interaction Information:

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 60196

gene/protein

RPTOR

is_part_of

complex/PPI

mTORC1 complex

Comment In the mTORC1 complex mTOR can interact with the proline-rich AKT substrate 40 kDa (pras40) with an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 60998

gene/protein

AKT1S1

interacts (colocalizes) with

gene/protein

MTOR

with an inhibitory effect on the kinase activity
Drugbank entries Show/Hide entries for MTOR
Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 60999

gene/protein

TTI1

interacts (colocalizes) with

gene/protein

TELO2

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61000

complex/PPI

TTI1-TELO2 complex

is_part_of

complex/PPI

mTORC1 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61001

complex/PPI

TTI1-TELO2 complex

is_part_of

complex/PPI

mTORC2 complex

Comment In the mTORC1 complex mTOR can interact with the proline-rich AKT substrate 40 kDa (pras40) with an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61002

gene/protein

AKT1S1

interacts (colocalizes) with

complex/PPI

mTORC1 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61003

gene/protein

DEPTOR

is_part_of

complex/PPI

mTORC1 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61004

gene/protein

DEPTOR

is_part_of

complex/PPI

mTORC2 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61005

gene/protein

MLST8

is_part_of

complex/PPI

mTORC1 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61006

gene/protein

MLST8

is_part_of

complex/PPI

mTORC2 complex

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61007

gene/protein

RPTOR

affects_activity of

gene/protein

MTOR

by interacting differently under opposite nutrient conditions.
Drugbank entries Show/Hide entries for MTOR
Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61008

environment

nutrient-rich condition

affects_activity of

gene/protein

RPTOR

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61009

affects_activity of

gene/protein

RPTOR

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61010

gene/protein

RPTOR

increases_activity of

complex/PPI

mTORC1 complex

Under nutrient-rich conditions RAPTOR positively modulates the mTORC1 pathway.
Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61011

gene/protein

RPTOR

decreases_activity of

complex/PPI

mTORC1 complex

Under starvation conditions RAPTOR exerts an inhibitory effect on the mTORC1 complex.
Comment In the mTORC1 complex mTOR can interact with the proline-rich AKT substrate 40 kDa (pras40) with an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61012

gene/protein

AKT1S1

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for MTOR
Comment In the mTORC1 complex mTOR can interact with the proline-rich AKT substrate 40 kDa (pras40) with an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61013

gene/protein

AKT1S1

decreases_activity of

complex/PPI

mTORC1 complex

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61014

environment

nutrient-rich condition

increases_activity of

complex/PPI

mTORC1 complex

Comment Raptor is a scaffold protein that regulates the kinase activity of mTOR by interacting differently under opposite nutrient conditions. Under nutrient-rich conditions it positively modulates the mTORC1 pathway, but in starvation it asscociates with the complex in a different way, exerting an inhibitory effect on the kinase activity.
Formal Description
Interaction-ID: 61015

decreases_activity of

complex/PPI

mTORC1 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61016

gene/protein

TTI1

is_part_of

complex/PPI

TTI1-TELO2 complex

Comment Other proteins may be found in both complexes, mTORC1 and mTORC2: the G protein beta-subunit-like protein (GbetaL), the mTOR inhibitor known as the DEP domain-containing mTOR-interacting protein (deptor), and the Tti1/Tel2 complex.
Formal Description
Interaction-ID: 61017

gene/protein

TELO2

is_part_of

complex/PPI

TTI1-TELO2 complex

Comment Amino acids are considered the most important mTOR pathway activators and, among them leucine and arginine in particular are able to stimulate mTORC1 strongly.
Formal Description
Interaction-ID: 61018

drug/chemical compound

Leucine

increases_activity of

complex/PPI

mTORC1 complex

strongly
Comment Amino acids are considered the most important mTOR pathway activators and, among them leucine and arginine in particular are able to stimulate mTORC1 strongly.
Formal Description
Interaction-ID: 61019

drug/chemical compound

Arginine

increases_activity of

complex/PPI

mTORC1 complex

strongly
Comment The main upstream key point in mTORC1 regulation is the protein complex containing tuberous sclerosis proteins 1 and 2 (TSC1/2) which convert Rheb in its inactive status bound to GDP. Rheb only in the GTP-bound form positively interacts with mTORC1. Thus, TSC1/2 inhibits mTOR kinase activity through Rheb inactivation.
Formal Description
Interaction-ID: 61020

complex/PPI

TSC1-TSC2 complex

decreases_activity of

gene/protein

RHEB

via converting Rheb in its inactive status bound to GDP (Rheb only in the GTP-bound form positively interacts with mTORC1).
Drugbank entries Show/Hide entries for RHEB
Comment Insulin and growth factors activate mTORC1 by TSC1/2 inhibition that is mediated by protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and ribosomal S6 kinase (RSK1).
Formal Description
Interaction-ID: 61021

complex/PPI

Insulin

increases_activity of

complex/PPI

mTORC1 complex

by TSC1/2 inhibition
Comment TSC1/2 inhibition also results from cytokine-mediated IkappaB kinase beta (IKKbeta) activation.
Formal Description
Interaction-ID: 61022

gene/protein

IKBKB

affects_activity of

complex/PPI

TSC1-TSC2 complex

Drugbank entries Show/Hide entries for IKBKB
Comment GSK3B stimulates TSC2 by phosphorylation and therefore is a negative regulator of mTORC1.
Formal Description
Interaction-ID: 61023

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

TSC2

therefore acting as negative regulator of mTORC1.
Drugbank entries Show/Hide entries for GSK3B
Comment Hypoxia and DNA damage also modulate mTORC1 with an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Formal Description
Interaction-ID: 61024

phenotype

hypoxia

affects_activity of

complex/PPI

mTORC1 complex

via an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Comment The main upstream key point in mTORC1 regulation is the protein complex containing tuberous sclerosis proteins 1 and 2 (TSC1/2) which convert Rheb in its inactive status bound to GDP. Rheb only in the GTP-bound form positively interacts with mTORC1. Thus, TSC1/2 inhibits mTOR kinase activity through Rheb inactivation.
Formal Description
Interaction-ID: 61026

complex/PPI

TSC1-TSC2 complex

decreases_activity of

complex/PPI

mTORC1 complex

through Rheb inactivation.
Comment The main upstream key point in mTORC1 regulation is the protein complex containing tuberous sclerosis proteins 1 and 2 (TSC1/2) which convert Rheb in its inactive status bound to GDP. Rheb only in the GTP-bound form positively interacts with mTORC1. Thus, TSC1/2 inhibits mTOR kinase activity through Rheb inactivation.
Formal Description
Interaction-ID: 61027

gene/protein

TSC1

is_part_of

complex/PPI

TSC1-TSC2 complex

Comment The main upstream key point in mTORC1 regulation is the protein complex containing tuberous sclerosis proteins 1 and 2 (TSC1/2) which convert Rheb in its inactive status bound to GDP. Rheb only in the GTP-bound form positively interacts with mTORC1. Thus, TSC1/2 inhibits mTOR kinase activity through Rheb inactivation.
Formal Description
Interaction-ID: 61028

gene/protein

TSC2

is_part_of

complex/PPI

TSC1-TSC2 complex

Comment Insulin and growth factors activate mTORC1 by TSC1/2 inhibition that is mediated by protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and ribosomal S6 kinase (RSK1).
Formal Description
Interaction-ID: 61030

gene/protein

MAPK3

affects_activity of

complex/PPI

mTORC1 complex

Drugbank entries Show/Hide entries for MAPK3
Comment Insulin and growth factors activate mTORC1 by TSC1/2 inhibition that is mediated by protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and ribosomal S6 kinase (RSK1).
Formal Description
Interaction-ID: 61031

gene/protein

MAPK1

affects_activity of

complex/PPI

mTORC1 complex

Drugbank entries Show/Hide entries for MAPK1
Comment Insulin and growth factors activate mTORC1 by TSC1/2 inhibition that is mediated by protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and ribosomal S6 kinase (RSK1).
Formal Description
Interaction-ID: 61032

gene/protein

AKT1

affects_activity of

complex/PPI

mTORC1 complex

Drugbank entries Show/Hide entries for AKT1
Comment Insulin and growth factors activate mTORC1 by TSC1/2 inhibition that is mediated by protein kinase B (Akt), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and ribosomal S6 kinase (RSK1).
Formal Description
Interaction-ID: 61033

gene/protein

RPS6KA1

affects_activity of

complex/PPI

mTORC1 complex

Drugbank entries Show/Hide entries for RPS6KA1
Comment GSK3B stimulates TSC2 by phosphorylation and therefore is a negative regulator of mTORC1.
Formal Description
Interaction-ID: 61041

gene/protein

GSK3B

decreases_activity of

complex/PPI

mTORC1 complex

by increasing the TSC2 phosphorylation.
Drugbank entries Show/Hide entries for GSK3B
Comment Hypoxia and DNA damage also modulate mTORC1 with an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Formal Description
Interaction-ID: 61042

decreases_activity of

complex/PPI

mTORC1 complex

via an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Comment Hypoxia and DNA damage also modulate mTORC1 with an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Formal Description
Interaction-ID: 61044

affects_activity of

gene/protein

DDIT4

Comment Hypoxia and DNA damage also modulate mTORC1 with an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Formal Description
Interaction-ID: 61046

gene/protein

DDIT4

decreases_activity of

complex/PPI

mTORC1 complex

Comment Hypoxia and DNA damage also modulate mTORC1 with an inhibitory effect mediated by DNA damage response 1 (REDD1) and TSC1/2 stimulation.
Formal Description
Interaction-ID: 61050

phenotype

hypoxia

affects_activity of

gene/protein

DDIT4

Comment The best characterized effect of mTORC1 activation is increased protein synthesis, mainly mediated by the phosphorylation of 70K ribosomal protein S6 kinase 1 (p70S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) - events of positively regulated translation.
Formal Description
Interaction-ID: 61434

complex/PPI

mTORC1 complex

increases_activity of

process

translation

mediated by the phosphorylation of 70K ribosomal protein S6 kinase 1 (p70S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1).
Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61435

complex/PPI

mTORC1 complex

decreases_activity of

process

autophagy

concerning protein and organelle degradation.
Comment mTORC1 activation also induces changes in energy metabolism, improving glycolysis-derived energy production by stimulating glucose uptake and glycolysis.
Formal Description
Interaction-ID: 61436

complex/PPI

mTORC1 complex

increases_activity of

Comment mTORC1 mediates an increase in hypoxia-inducible factor 1alpha (HIF1alpha) translation, which triggers the expression of glucose transporters and glyolytic enzymes, thereby promoting a switch from mitochondrial oxidative metabolism to glycolysis.
Formal Description
Interaction-ID: 61438

complex/PPI

mTORC1 complex

increases_expression of

gene/protein

HIF1A

triggering the expression of glucose transporters and glyolytic enzymes.
Drugbank entries Show/Hide entries for HIF1A
Comment mTORC2 is localized at the mitochondria-associated endoplasmic reticulum (ER) membrane and ER stress affects the kinase activity.
Formal Description
Interaction-ID: 61440

complex/PPI

mTORC2 complex

is localized in

cellular component

endoplasmic reticulum

Comment mTORC2 phosphorylates newly synthesized Akt and PKCalpha at the level of a highly conserved region typical of AGC kinases, thus facilitating its carboxyl-terminal folding and stabilizing the protein. In the presence of growth factors, Akt is further phosphorylated at other sites by mTORC2 and PDK1 (3-phosphoinositide-dependent protein kinase-1, leading to full Akt activation.
Formal Description
Interaction-ID: 61442

complex/PPI

mTORC2 complex

increases_phosphorylation of

gene/protein

PRKCA

Drugbank entries Show/Hide entries for PRKCA
Comment Akt is upstream of TSC1/2, which means that mTORC2 supports mTORC1 activity.
Formal Description
Interaction-ID: 61443

complex/PPI

mTORC2 complex

increases_activity of

complex/PPI

mTORC1 complex

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61489

process

autophagy

increases_activity of

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61490

process

autophagy

increases_activity of

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61491

complex/PPI

mTORC1 complex

affects_activity of

gene/protein

ULK1

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61492

complex/PPI

mTORC1 complex

affects_activity of

gene/protein

RB1CC1

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61493

complex/PPI

mTORC1 complex

affects_activity of

gene/protein

ATG13

Comment Protein and organelle degradation mediated by autophagy is inhibited by mTORC1 action on the protein complex containing the autophagy-initiating kinase ULK1 (unc-51-like kinase 1) and two additional protein factors, FAK-family interacting protein of 200 K /FIP200) and autophagy-related protein 13 (Atg13). At the same time, the autophagic process is impaired by the negative modulation exerted by mTORC1 on transcription factor EB (TFEB), which is a master regulator in lysosome biogenesis.
Formal Description
Interaction-ID: 61494

complex/PPI

mTORC1 complex

affects_activity of

gene/protein

TFEB

a master regulator in lysosome biogenesis.
Comment mTORC1 mediates an increase in hypoxia-inducible factor 1alpha (HIF1alpha) translation, which triggers the expression of glucose transporters and glyolytic enzymes, thereby promoting a switch from mitochondrial oxidative metabolism to glycolysis.
Formal Description
Interaction-ID: 61501

gene/protein

HIF1A

increases_expression of

gene/protein

SLC2A

Drugbank entries Show/Hide entries for HIF1A
Comment mTORC1 mediates an increase in hypoxia-inducible factor 1alpha (HIF1alpha) translation, which triggers the expression of glucose transporters and glyolytic enzymes, thereby promoting a switch from mitochondrial oxidative metabolism to glycolysis.
Formal Description
Interaction-ID: 61503

gene/protein

HIF1A

increases_expression of

gene/protein

glucolytic enzyme

promoting a switch from mitochondrial oxidative metabolism to glycolysis.
Drugbank entries Show/Hide entries for HIF1A
Comment mTORC2 phosphorylates newly synthesized Akt and PKCalpha at the level of a highly conserved region typical of AGC kinases, thus facilitating its carboxyl-terminal folding and stabilizing the protein. In the presence of growth factors, Akt is further phosphorylated at other sites by mTORC2 and PDK1 (3-phosphoinositide-dependent protein kinase-1, leading to full Akt activation.
Formal Description
Interaction-ID: 61505

complex/PPI

mTORC2 complex

increases_phosphorylation of

gene/protein

AKT1

In the presence of growth factors.
Drugbank entries Show/Hide entries for AKT1
Comment mTORC2 phosphorylates newly synthesized Akt and PKCalpha at the level of a highly conserved region typical of AGC kinases, thus facilitating its carboxyl-terminal folding and stabilizing the protein. In the presence of growth factors, Akt is further phosphorylated at other sites by mTORC2 and PDK1 (3-phosphoinositide-dependent protein kinase-1, leading to full Akt activation.
Formal Description
Interaction-ID: 61506

gene/protein

PDK1

increases_phosphorylation of

gene/protein

AKT1

In the presence of growth factors.
Drugbank entries Show/Hide entries for PDK1 or AKT1
Comment AMPK inhibits cholesterol synthesis by phosphorylating the rate-limiting enzyme HMGCR, and triglyceride synthesis.
Formal Description
Interaction-ID: 61565

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

HMGCR

hereby inhibiting the cholesterol synthesis.
Drugbank entries Show/Hide entries for HMGCR
Comment AMPK inhibits cholesterol synthesis by phosphorylating the rate-limiting enzyme HMGCR, and triglyceride synthesis.
Formal Description
Interaction-ID: 61566

complex/PPI

AMPK

decreases_activity of

by phosphorylating the rate-limiting enzyme HMGCR.
Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61567

gene/protein

SIRT1

is localized in

cellular component

nucleus

Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61568

gene/protein

SIRT6

is localized in

cellular component

nucleus

Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61569

gene/protein

SIRT7

is localized in

cellular component

nucleus

Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61570

gene/protein

SIRT3

is localized in

cellular component

mitochondrion

Drugbank entries Show/Hide entries for SIRT3
Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61571

gene/protein

SIRT4

is localized in

cellular component

mitochondrion

Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61572

gene/protein

SIRT5

is localized in

cellular component

mitochondrion

Drugbank entries Show/Hide entries for SIRT5
Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61573

gene/protein

SIRT2

is localized in

cellular component

cytoplasm

Comment The NAD+ biosynthetic rate is crucial in Sirt1 regulation. Only in the presence of the cosubstrate NAD+ does the reaction lead to removal of actyl groups from an acetylated substrate, releasing nicotinamide, 2'-O-acetyl-ADP-ribose and the deacetylated target (e.g. histonic lysines).
Formal Description
Interaction-ID: 61617

drug/chemical compound

NAD+

affects_activity of

gene/protein

SIRT1

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61620

environment

exercise

increases_quantity of

drug/chemical compound

NAD+

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molcular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61621

gene/protein

SIRT1

interacts (colocalizes) with

complex/PPI

CLOCK-BMAL1 complex

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61622

environment

fasting

increases_quantity of

drug/chemical compound

NAD+

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61623

environment

caloric restriction

increases_quantity of

drug/chemical compound

NAD+

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61624

environment

exercise

increases_activity of

gene/protein

SIRT1

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61625

environment

fasting

increases_activity of

gene/protein

SIRT1

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61626

environment

caloric restriction

increases_activity of

gene/protein

SIRT1

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molcular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61627

gene/protein

ARNTL

is_part_of

complex/PPI

CLOCK-BMAL1 complex

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molcular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61628

gene/protein

CLOCK

is_part_of

complex/PPI

CLOCK-BMAL1 complex

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molcular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61629

complex/PPI

CLOCK-BMAL1 complex

affects_activity of

process

circadian clock

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molecular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61630

gene/protein

SIRT1

affects_activity of

process

circadian clock

Comment Several signals converge on Sirt1 to stimulate its protein deacetylase activity, which uses NAD+ as a cosubstrate and releases acetyl-ADP-ribose and nicotinamide (NAM).
Formal Description
Interaction-ID: 61631

gene/protein

SIRT1

increases_quantity of

drug/chemical compound

O-Acetyl-ADP-ribose

Comment Several signals converge on Sirt1 to stimulate its protein deacetylase activity, which uses NAD+ as a cosubstrate and releases acetyl-ADP-ribose and nicotinamide (NAM).
Formal Description
Interaction-ID: 61632

gene/protein

SIRT1

increases_quantity of

drug/chemical compound

Nicotinamide

Drugbank entries Show/Hide entries for
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61635

gene/protein

SIRT1

affects_activity of

gene/protein

TP53

Drugbank entries Show/Hide entries for TP53
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61641

gene/protein

SIRT1

affects_activity of

gene/protein

PPARGC1A

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61642

gene/protein

SIRT1

affects_activity of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61643

gene/protein

SIRT1

affects_activity of

gene/protein

EPAS1

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61644

gene/protein

SIRT1

affects_activity of

gene/protein

NR1H

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61645

gene/protein

SIRT1

affects_activity of

gene/protein

GPR85

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61646

gene/protein

SIRT1

affects_activity of

gene/protein

NR1H4

Drugbank entries Show/Hide entries for NR1H4
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61647

gene/protein

SIRT1

affects_activity of

gene/protein

NFKB1

Drugbank entries Show/Hide entries for NFKB1
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61648

gene/protein

SIRT1

affects_activity of

gene/protein

PER2

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61649

gene/protein

SIRT1

affects_activity of

gene/protein

CRTC2

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61650

gene/protein

SIRT1

affects_activity of

gene/protein

E2F1

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61651

gene/protein

SIRT1

affects_activity of

gene/protein

XRCC6

Comment Resveratrol cannot stimulate Sirt1 activity without a functional AMPK. It is proposed that Sirt1 is a downstream AMPK effector.
Formal Description
Interaction-ID: 61652

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

SIRT1

depending on a functional AMPK.
Drugbank entries Show/Hide entries for Resveratrol
Comment Hydroxytyrosol, a molecule mainly derived from olives, increases Sirt1 expression.
Formal Description
Interaction-ID: 61653

drug/chemical compound

Hydroxytyrosol

increases_expression of

gene/protein

SIRT1

Comment Sirt1 interacts with and deacetylates FoxO transcription factors.
Formal Description
Interaction-ID: 61654

gene/protein

SIRT1

interacts (colocalizes) with

gene/protein

FOXO

Comment Sirt1 interacts with and deacetylates FoxO transcription factors.
Formal Description
Interaction-ID: 61655

gene/protein

SIRT1

decreases_acetylation of

gene/protein

FOXO

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61656

gene/protein

SIRT1

decreases_acetylation of

gene/protein

ATG5

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61657

gene/protein

SIRT1

decreases_acetylation of

gene/protein

ATG7

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61658

gene/protein

SIRT1

decreases_acetylation of

gene/protein

GABARAPL

Comment AMPK's autophagy-promoting activity results from direct phosphorylation of ULK1 independent of mTOR's control of autophagy, as well as from inhibition of an mTOR pathway through AMPK-mediated phosphorylation of raptor and TSC2.
Formal Description
Interaction-ID: 61668

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

ULK1

Comment AMPK's autophagy-promoting activity results from direct phosphorylation of ULK1 independent of mTOR's control of autophagy, as well as from inhibition of an mTOR pathway through AMPK-mediated phosphorylation of raptor and TSC2.
Formal Description
Interaction-ID: 61669

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

RPTOR

Comment AMPK's autophagy-promoting activity results from direct phosphorylation of ULK1 independent of mTOR's control of autophagy, as well as from inhibition of an mTOR pathway through AMPK-mediated phosphorylation of raptor and TSC2.
Formal Description
Interaction-ID: 61670

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

TSC2

Comment Likely via mTOR inhibition, AMPK negatively modulates the expression of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines, which are essential for cell growth and proliferation.
Formal Description
Interaction-ID: 61671

complex/PPI

AMPK

decreases_expression of

gene/protein

ODC1

Drugbank entries Show/Hide entries for ODC1
Comment It was found that resveratrol and spermidine in human cultured cells promote autophagy in a Sirt1-dependent and Sirt1-independent way, respectively, even if these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome.
Formal Description
Interaction-ID: 61672

drug/chemical compound

Resveratrol

increases_activity of

process

autophagy

in human cultured cells; in a Sirt1-dependent and Sirt1-independent way.
Drugbank entries Show/Hide entries for Resveratrol
Comment It was found that resveratrol and spermidine in human cultured cells promote autophagy in a Sirt1-dependent and Sirt1-independent way, respectively, even if these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome.
Formal Description
Interaction-ID: 61673

drug/chemical compound

Spermidine

increases_activity of

process

autophagy

in human cultured cells; in a Sirt1-dependent and Sirt1-independent way.
Drugbank entries Show/Hide entries for Spermidine
Comment It has been demonstrated that AMPK does not directly phosphorylate SIRT1, but the effect of this kinase on lipid oxidation is to modify the NAD+/NADH ratio, thus modulating SIRT1 deacetylase activity. Some evidence indicates that the expression of Nampt (Nicotinamide phosphoribosyl-transferase), which is involved in the synthesis of NAD+ by the NAD+ salvage pathway, is induced by AMPK.
Formal Description
Interaction-ID: 61674

complex/PPI

AMPK

affects_activity of

gene/protein

SIRT1

via modifying the NAD+/NADH ratio.
Comment LKB1, upstream of AMPK activation, is target of Sirt1, which may regulate its acetylation status, intracellular localization, and activity.
Formal Description
Interaction-ID: 61676

gene/protein

SIRT1

affects_activity of

gene/protein

STK11

Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61677

gene/protein

SIRT1

decreases_expression of

gene/protein

MTOR

if SIRT1 is overexpressed, concerning the mTOR protein level.
Drugbank entries Show/Hide entries for MTOR
Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61679

gene/protein

SIRT1

decreases_activity of

gene/protein

MTOR

if SIRT1 is overexpressed.
Drugbank entries Show/Hide entries for MTOR
Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61680

gene/protein

SIRT1

decreases_activity of

process

TOR signaling

if SIRT1 is overexpressed.