Page last updated: 2024-10-24

regulation of protein modification process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the covalent alteration of one or more amino acid residues within a protein. [GOC:mah, GOC:tb]

Regulation of protein modification is a complex and fundamental process in cellular biology, essential for maintaining proper cellular function and responding to various stimuli. It involves a intricate network of enzymes, signaling pathways, and regulatory mechanisms that control the addition, removal, or modification of chemical groups to proteins. These modifications can alter protein structure, activity, localization, and interactions, thereby impacting a wide range of cellular processes.

**Key Aspects of Regulation:**

1. **Enzymatic Control:** Specific enzymes play crucial roles in adding or removing modifications. These enzymes, known as kinases, phosphatases, acetylases, deacetylases, ubiquitin ligases, and deubiquitinases, among others, exhibit high specificity for their target proteins and modification sites.
2. **Signaling Pathways:** External and internal cues, such as growth factors, hormones, stress signals, and nutrient availability, activate signaling cascades that ultimately modulate the activity of modification enzymes. These pathways often involve phosphorylation events, second messengers, and protein-protein interactions, contributing to the dynamic nature of regulation.
3. **Protein-Protein Interactions:** The interaction between proteins can influence the accessibility of modification sites, regulate enzyme activity, or form complexes that target specific substrates.
4. **Post-Translational Modifications:** Protein modifications are often dynamic and reversible. This allows for rapid and fine-tuned regulation of cellular processes in response to changing environmental conditions.

**Types of Protein Modifications:**

- **Phosphorylation:** Addition of a phosphate group, commonly catalyzed by kinases. It can activate or deactivate proteins, alter their interactions, or create binding sites for other molecules.
- **Acetylation:** Addition of an acetyl group, primarily occurring on lysine residues. It can influence protein stability, interactions, and localization.
- **Ubiquitination:** Attachment of ubiquitin, a small protein, which can target proteins for degradation, modulate their activity, or regulate their localization.
- **Glycosylation:** Addition of sugar molecules, impacting protein folding, stability, and interactions.
- **Methylation:** Addition of a methyl group, affecting protein structure and interactions.

**Biological Importance:**

- **Cellular Signaling:** Protein modification plays a crucial role in signal transduction pathways, mediating responses to external stimuli and coordinating cellular activities.
- **Cellular Function:** Regulation of protein modification is essential for various cellular processes, including transcription, translation, cell cycle progression, and apoptosis.
- **Disease Development:** Dysregulation of protein modification has been implicated in numerous diseases, including cancer, neurodegenerative disorders, and metabolic diseases.

**Overall, the regulation of protein modification is a complex and highly regulated process that is essential for maintaining cellular homeostasis and responding to environmental cues. It involves a dynamic interplay of enzymes, signaling pathways, and protein interactions that ultimately control the activity, structure, and fate of proteins within cells.**'
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Proteins (1)

ProteinDefinitionTaxonomy
Histone-lysine N-methyltransferase EHMT2A histone-lysine N-methyltransferase, H3 lysine-9 specific 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96KQ7]Homo sapiens (human)

Compounds (32)

CompoundDefinitionClassesRoles
disulfiramorganic disulfide;
organosulfur acaricide
angiogenesis inhibitor;
antineoplastic agent;
apoptosis inducer;
EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor;
EC 3.1.1.1 (carboxylesterase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
ferroptosis inducer;
fungicide;
NF-kappaB inhibitor
ebselenebselen : A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase.benzoselenazoleanti-inflammatory drug;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
EC 3.1.3.25 (inositol-phosphate phosphatase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 3.5.4.1 (cytosine deaminase) inhibitor;
EC 5.1.3.2 (UDP-glucose 4-epimerase) inhibitor;
enzyme mimic;
ferroptosis inhibitor;
genotoxin;
hepatoprotective agent;
neuroprotective agent;
radical scavenger
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
thiramthiram : An organic disulfide that results from the formal oxidative dimerisation of N,N-dimethyldithiocarbamic acid. It is widely used as a fungicidal seed treatment.

Thiram: A dithiocarbamate chemical, used commercially in the rubber processing industry and as a fungicide. In vivo studies indicate that it inactivates the enzyme GLUTATHIONE REDUCTASE. It has mutagenic activity and may induce chromosomal aberrations.
organic disulfideantibacterial drug;
antifungal agrochemical;
antiseptic drug
cystamine dihydrochloride
cysteaminecysteamine : An amine that consists of an ethane skeleton substituted with a thiol group at C-1 and an amino group at C-2.

Cysteamine: A mercaptoethylamine compound that is endogenously derived from the COENZYME A degradative pathway. The fact that cysteamine is readily transported into LYSOSOMES where it reacts with CYSTINE to form cysteine-cysteamine disulfide and CYSTEINE has led to its use in CYSTINE DEPLETING AGENTS for the treatment of CYSTINOSIS.
amine;
thiol
geroprotector;
human metabolite;
mouse metabolite;
radiation protective agent
gliotoxingliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.

Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
dipeptide;
organic disulfide;
organic heterotetracyclic compound;
pyrazinoindole
antifungal agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
immunosuppressive agent;
mycotoxin;
proteasome inhibitor
9,10-anthraquinone9,10-anthraquinone : An anthraquinone that is anthracene in which positions 9 and 10 have been oxidised to carbonyls.anthraquinone
1,4-naphthoquinone1,4-naphthoquinone : The parent structure of the family of 1,4-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 4 of the naphthalene ring. Derivatives have pharmacological properties.

naphthoquinone : A polycyclic aromatic ketone metabolite of naphthalene.
1,4-naphthoquinones
azacitidine5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.

Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
N-glycosyl-1,3,5-triazine;
nucleoside analogue
antineoplastic agent
ninhydrinninhydrin : A member of the class of indanones that is indane-1,3-dione bearing two additional hydroxy substituents at position 2.

Ninhydrin: 2,2-Dihydroxy-1H-indene-1,3-(2H)-dione. Reagent toxic to skin and mucus membranes. It is used in chemical assay for peptide bonds, i.e., protein determinations and has radiosensitizing properties.
aromatic ketone;
beta-diketone;
indanones;
ketone hydrate
colour indicator;
human metabolite
diphenyldiselenidediphenyldiselenide: structure given in first source
benzeneseleninic acidbenzeneseleninic acid: structure given in first source
sodium selenatesodium selenate : An inorganic sodium salt having selenate as the counterion.inorganic sodium saltanticonvulsant;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor;
fertilizer
2,2'-dipyridyl disulfide2,2'-dipyridyl disulfide: disulfide is an important moiety in this cpd

aldrithiol : A member of the class of pyridines that is pyridine which is substituted by a pyridin-2-yldisulfanediyl group at position 2. It is a reagent used in molecular biology as an oxidizing agent. Also used in peptide synthesis and for detecting thiols.
organic disulfide;
pyridines
oxidising agent
glutathione disulfideGlutathione Disulfide: A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.glutathione derivative;
organic disulfide
Escherichia coli metabolite;
mouse metabolite
sinefunginadenosines;
non-proteinogenic alpha-amino acid
antifungal agent;
antimicrobial agent
bisdethiobis(methylthio)gliotoxinbisdethiobis(methylthio)gliotoxin: structure given in first source; a platelet activating factor antagonist
s-adenosylhomocysteineS-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine.

S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
adenosines;
amino acid zwitterion;
homocysteine derivative;
homocysteines;
organic sulfide
cofactor;
EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor;
EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor;
epitope;
fundamental metabolite
decitabine2'-deoxyribonucleoside
ditiocarb sodiumorganic molecular entity
verticillinsverticillins: 3 antibiotics isolated from imperfect fungus Verticillium: verticillin A, verticillin B (mono-3-hydroxymethyl analog of verticillin A), & verticillin C (differs from verticillin B in that 1 of dioxopiperazine rings has a trisulfide rather than a disulfide bridge; active against gram-positive bacteria & mycobacteria but not against gram-negative bacteria & fungi; RN given refers to cpd with unknown MF; structure (verticillins A & B))
azodicarbonamideorganic molecular entity
chetomin
sgi-1027SGI-1027: inhibits DNA methyltransferase 1; structure in first source
bix 01294piperidines
unc 0638UNC 0638: inhibits lysine methyltransferases G9a and GLP; structure in first sourcequinazolines
unc 03217-(2-(2-(dimethylamino)ethoxy)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine: a G9a antagonist; structure in first sourcequinazolines
unc 0631N-(1-(cyclohexylmethyl)piperidin-4-yl)-2-(4-isopropyl-1,4-diazepan-1-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine: inhibits protein lysine methyltransferase G9a; structure in first source
gsk343GSK343 : A member of the class of indazoles that is 1-isopropyl-1H-indazole-4-carboxamide in which the nitrogen of the carboxamide group is substituted by a (6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl group and in which the indazole ring is substituted at position 6 by a 2-(4-methylpiperazin-1-yl)pyridin-4-yl group. A highly potent and selective EZH2 inhibitor (IC50 = 4 nM).

GSK343: an EZH2 methyltransferase inhibitor
aminopyridine;
indazoles;
N-alkylpiperazine;
N-arylpiperazine;
pyridone;
secondary carboxamide
antineoplastic agent;
apoptosis inducer;
EC 2.1.1.43 (enhancer of zeste homolog 2) inhibitor
brd4770benzimidazoles
6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source