Gene Targets > protein desuccinylation
Page last updated: 2024-10-24

protein desuccinylation

Definition

Target type: biologicalprocess

The removal of a succinyl group (CO-CH2-CH2-CO) from a residue in a peptide or protein. [GOC:sp, PMID:22076378]

Protein desuccinylation is a crucial post-translational modification (PTM) that involves the removal of succinyl groups (C4H4O3) from lysine residues within proteins. Succinylation is a dynamic process that can alter protein structure, function, and interactions.

Desuccinylation is catalyzed by a family of enzymes known as desuccinylases, which belong to the sirtuin family. These enzymes utilize NAD+ as a cofactor and hydrolyze the succinyl group from lysine residues, releasing succinate and NADH.

Desuccinylation plays a critical role in various cellular processes, including:

1. **Metabolic regulation:** Desuccinylation can modulate the activity of enzymes involved in metabolic pathways, such as the citric acid cycle and glycolysis.
2. **Gene expression:** Desuccinylation can influence the activity of transcription factors, affecting gene expression patterns.
3. **Cellular signaling:** Desuccinylation can regulate the function of signaling proteins, impacting downstream pathways.
4. **Stress response:** Desuccinylation can contribute to the cellular response to stress conditions, such as oxidative stress or nutrient deprivation.
5. **Disease pathogenesis:** Dysregulation of desuccinylation has been implicated in the development of various diseases, including cancer, neurodegenerative disorders, and metabolic disorders.

The process of desuccinylation is highly dynamic and reversible, and the balance between succinylation and desuccinylation is crucial for maintaining cellular homeostasis. This balance is influenced by various factors, including cellular metabolism, stress levels, and the expression levels of succinyltransferases and desuccinylases.

In summary, desuccinylation is a critical PTM that modulates protein function and plays a role in numerous cellular processes. Understanding the mechanisms and regulation of desuccinylation is essential for elucidating its role in health and disease.'
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Proteins (1)

ProteinDefinitionTaxonomy
NAD-dependent protein deacylase sirtuin-5, mitochondrialAn NAD-dependent deacetylase sirtuin-5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NXA8]Homo sapiens (human)

Compounds (27)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
anthralinanthralin : An anthracene compound derived by the substitution of -OH groups for hydrogen at C-1 and C-8, and with an oxo group at C-9.

Anthralin: An anthracene derivative that disrupts MITOCHONDRIA function and structure and is used for the treatment of DERMATOSES, especially PSORIASIS. It may cause FOLLICULITIS.		anthracenesantipsoriatic
valproic acidvalproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.		branched-chain fatty acid;
branched-chain saturated fatty acid		anticonvulsant;
antimanic drug;
EC 3.5.1.98 (histone deacetylase) inhibitor;
GABA agent;
neuroprotective agent;
psychotropic drug;
teratogenic agent
4-phenylbutyric acid4-phenylbutyric acid : A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the gamma-globin gene and affects hPPARgamma activation.

4-phenylbutyric acid: RN refers to the parent cpd		monocarboxylic acidantineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor;
prodrug
probucolprobucol : A dithioketal that is propane-2,2-dithiol in which the hydrogens attached to both sulfur atoms are replaced by 3,5-di-tert-butyl-4-hydroxyphenyl groups. An anticholesteremic drug with antioxidant and anti-inflammatory properties, it is used to treat high levels of cholesterol in blood.

Probucol: A drug used to lower LDL and HDL cholesterol yet has little effect on serum-triglyceride or VLDL cholesterol. (From Martindale, The Extra Pharmacopoeia, 30th ed, p993).		dithioketal;
polyphenol		anti-inflammatory drug;
anticholesteremic drug;
antilipemic drug;
antioxidant;
cardiovascular drug
fenofibratebenzochromenone;
delta-lactone;
naphtho-alpha-pyrone		platelet aggregation inhibitor;
Sir2 inhibitor
vorinostatvorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.		dicarboxylic acid diamide;
hydroxamic acid		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
suraminsuramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.

Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.		naphthalenesulfonic acid;
phenylureas;
secondary carboxamide		angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
rheindihydroxyanthraquinone
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid		plant metabolite
closantelclosantel : A racemate comprising equimolar amounts of (R)- and (S)-clostanel. An anthelmintic, it is used (as the dihydrate of the sodium salt) in veterinary medicine for the treatment of fluke and nematode infections.

closantel: structure

N-{5-chloro-4-[(4-chlorophenyl)(cyano)methyl]-2-methylphenyl}-2-hydroxy-3,5-diiodobenzamide : An aromatic amide resulting from the formal condensation of the carboxy group of 3,5-diiodosalicylic acid with the amino group of aniline substituted at positions 2, 4, and 5 by methyl, (4-chlorophenyl)(cyano)methyl, and methyl groups respectively.		aromatic amide;
monocarboxylic acid amide;
monochlorobenzenes;
nitrile;
organoiodine compound;
phenols
balsalazidebalsalazide : A monohydroxybenzoic acid consisting of 5-aminosalicylic acid (mesalazine) linked to 4-aminobenzoyl-beta-alanine via an azo bond.

balsalazide: a mesalamine 5-aminosalicylate prodrug; 99% of ingested drug remains intact through the stomach and is delivered to and activated in the colon; used for inflammatory bowel disease, ulcerative colitis and radiation-induced proctosigmoiditis but avoided in patients with known hypersensitivity reaction to salicylates or mesalamine; structure in first source
echinocystic acidtriterpenoid
fulvestrantfulvestrant : A 3-hydroxy steroid that is 17beta-estradiol in which the 7alpha hydrogen has been replaced by a nonyl group in which one of the hydrogens of the terminal methyl has been replaced by a (4,4,5,5,5-pentafluoropentyl)sulfinyl group. An estrogen receptor antagonist, it is used in the treatment of breast cancer.

Fulvestrant: An estradiol derivative and estrogen receptor antagonist that is used for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer.		17beta-hydroxy steroid;
3-hydroxy steroid;
organofluorine compound;
sulfoxide		antineoplastic agent;
estrogen antagonist;
estrogen receptor antagonist
nisoxetine hydrochloride
nsc 74859NSC 74859: inhibits Stat3 binding activity; structure in first source

S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid.		amidobenzoic acid;
monohydroxybenzoic acid;
tosylate ester		STAT3 inhibitor
4-(4-chloroanilino)-3-pyridinesulfonamidepyridines;
sulfonamide
4-phenoxyphenyl 4-hydroxypiperidine-1-carboxylatearomatic ether
sirtinolaldimine;
benzamides;
naphthols		anti-inflammatory agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Sir2 inhibitor
cambinolcambinol: inhibitor of human silent information regulator 2 enzymes; structure in first source
gw 7647GW 7647 : A monocarboxylic acid that is 2-(phenylsulfanyl)isobutyric acid in which the phenyl group is substituted at the para- position by a 3-aza-7-cyclohexylhept-1-yl group in which the nitrogen is acylated by a (cyclohexylamino)carbonyl group.

GW 7647: a PPAR-alpha agonist; structure in first source		aryl sulfide;
monocarboxylic acid;
ureas		PPARalpha agonist
ex 5276-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide : A member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine.

6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide: structure in first source		carbazoles;
monocarboxylic acid amide;
organochlorine compound
n-oleoyldopamineN-oleoyldopamine : A fatty amide resulting from the formal condensation of the carboxy group of oleic acid with the amino group of dopamine. Synthesised in catecholaminergic neurons, it crosses the blood-brain barrier and might be considered as a carrier of dopamine into the brain. It is a transient receptor potential vanilloid type 1 (TRPV1) receptor agonist.

N-oleoyldopamine: putative capsaicin receptor ligand; produces hyperalgesia; isolated from the brain		catechols;
fatty amide;
N-(fatty acyl)-dopamine;
secondary carboxamide		TRPV1 agonist
cefiximecephalosporinantibacterial drug;
drug allergen
N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamidebenzamides
methacyclinemethacycline : A tetracycline that is the 6-methylene analogue of oxytetracycline, obtained by formal dehydration at position 6.

Methacycline: A broad-spectrum semisynthetic antibiotic related to TETRACYCLINE but excreted more slowly and maintaining effective blood levels for a more extended period.
antimycin
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