Page last updated: 2024-10-24

protein targeting

Definition

Target type: biologicalprocess

The process of targeting specific proteins to particular regions of the cell, typically membrane-bounded subcellular organelles. Usually requires an organelle specific protein sequence motif. [GOC:ma]

Protein targeting is the process by which newly synthesized proteins are delivered to their correct destinations within the cell. This process is crucial for maintaining cellular function and is essential for many biological processes, including cell signaling, metabolism, and organelle biogenesis. The targeting process is highly selective, ensuring that each protein reaches its intended location and performs its specific function.

The first step in protein targeting is the synthesis of the protein on ribosomes. Ribosomes can be either free in the cytoplasm or attached to the endoplasmic reticulum (ER). The location of ribosome binding determines the initial targeting pathway.

For proteins destined for the cytoplasm, nucleus, mitochondria, or peroxisomes, ribosomes remain free in the cytoplasm. These proteins are synthesized and then either remain in the cytoplasm or are further transported to their specific destinations. For example, proteins with nuclear localization signals (NLS) will be imported into the nucleus.

Proteins targeted to the ER, Golgi apparatus, lysosomes, plasma membrane, or secretion are synthesized on ribosomes that bind to the ER. The signal recognition particle (SRP) recognizes a signal sequence on the nascent polypeptide chain and binds to it, halting translation. The SRP-ribosome complex then interacts with the SRP receptor on the ER membrane, initiating protein translocation.

During translocation, the nascent polypeptide chain crosses the ER membrane through a protein translocator. The signal sequence is cleaved off by a signal peptidase, and the protein folds into its correct conformation within the ER lumen.

After folding, proteins can be further modified in the ER, such as glycosylation. They then move to the Golgi apparatus, a series of flattened membrane-bound sacs, for further processing and sorting.

Proteins destined for the lysosomes are tagged with mannose-6-phosphate (M6P) in the Golgi. M6P receptors bind these proteins and deliver them to the lysosomes.

Proteins targeted for the plasma membrane are sorted in the trans-Golgi network and packaged into transport vesicles. These vesicles bud off from the Golgi and fuse with the plasma membrane, delivering the protein to the cell surface.

Proteins destined for secretion are packaged into secretory vesicles. These vesicles fuse with the plasma membrane and release their contents into the extracellular space.

The entire process of protein targeting is highly regulated and involves the interplay of numerous proteins and factors. This complex machinery ensures that each protein reaches its correct destination, enabling the cell to function efficiently.'
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Proteins (7)

ProteinDefinitionTaxonomy
14-3-3 protein zeta/deltaA 14-3-3 protein zeta/delta that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
60S ribosomal protein L11A eukaryotic-type large ribosomal subunit protein uL5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62913]Homo sapiens (human)
14-3-3 protein gammaA 14-3-3 protein gamma that is encoded in the genome of human. [PRO:DNx, UniProtKB:P61981]Homo sapiens (human)
14-3-3 protein beta/alphaA 14-3-3 protein beta/alpha that is encoded in the genome of human. [PRO:WCB, UniProtKB:P31946]Homo sapiens (human)
14-3-3 protein thetaA 14-3-3 protein theta that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27348]Homo sapiens (human)
Voltage-dependent calcium channel gamma-3 subunitA voltage-dependent calcium channel gamma-3 subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60359]Homo sapiens (human)
Potassium voltage-gated channel subfamily KQT member 3A voltage-gated potassium channel subunit KCNQ3 that is encoded in the genome of human. []Homo sapiens (human)

Compounds (15)

CompoundDefinitionClassesRoles
tacrinetacrine : A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease.

Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
acridines;
aromatic amine
EC 3.1.1.7 (acetylcholinesterase) inhibitor
N-(2-aminoethyl)-5-chloro-1-naphthalenesulfonamidenaphthalenes;
sulfonic acid derivative
nimodipinenimodipine : A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a (2-methoxyethoxy)carbonyl group at position 3, a m-nitrophenyl group at position 4, and an isopropoxycarbonyl group at position 5. An L-type calcium channel blocker, it acts particularly on cerebral circulation, and is used both orally and intravenously for the prevention and treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm.

Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
2-methoxyethyl ester;
C-nitro compound;
dicarboxylic acids and O-substituted derivatives;
diester;
dihydropyridine;
isopropyl ester
antihypertensive agent;
calcium channel blocker;
cardiovascular drug;
vasodilator agent
flupirtineflupirtine: RN given refers to parent cpd without isomeric designationaminopyridine
ezogabineezogabine : A substituted aniline that is benzene-1,2,4-triamine bearing ethoxycarbonyl and 4-fluorobenzyl substituents at positions N-1 and N-4 respectively. An anticonvulsant used to treat seizures associated with epilepsy in adults.

ezogabine: structure in first source
carbamate ester;
organofluorine compound;
secondary amino compound;
substituted aniline
anticonvulsant;
potassium channel modulator
bms204352BMS204352: a calcium-sensitive opener of maxi-K potassium channels; structure in first source
N-(2,4,6-trimethylphenyl)-3-bicyclo[2.2.1]heptanecarboxamidemonoterpenoid
n-(6-chloropyridin-3-yl)-4-fluorobenzamideN-(6-chloropyridin-3-yl)-4-fluorobenzamide: structure in first source
mrs2159MRS2159: an antagonist of both P2X1 and P2X7 receptors
ith 4012
gentamicin sulfate
ica 27243N-(6-Chloropyridin-3-yl)-3,4-difluorobenzamide: a KCNQ2/3 channel activator; structure in first source
a 803467A 803467: an Nav1.8 sodium channel blocker; structure in first source
r18 peptideR18 peptide: a 20-mer peptide, derived from a phage library, that binds 14-3-3 tau protein; amino acid sequence in first source
PF-06446846PF-06446846 : A triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9.

PF-06446846: inhibits translation of PCSK9 ;structure in first source
benzamides;
monochloropyridine;
piperidines;
tertiary carboxamide;
triazolopyridine
antilipemic drug;
EC 3.4.21.61 (kexin) inhibitor