Page last updated: 2024-10-24

localization within membrane

Definition

Target type: biologicalprocess

Any process in which a substance or cellular entity, such as a protein complex or organelle, is transported to, and/or maintained in, a specific location within a membrane. [GOC:ai]

Localization within a membrane is a fundamental biological process that involves the targeting, delivery, and anchoring of proteins and lipids to specific membrane compartments. These membranes, acting as dynamic barriers within cells, play crucial roles in compartmentalizing cellular functions, facilitating signal transduction, and mediating transport. The process of localization encompasses several distinct stages, each driven by specific molecular mechanisms.

1. **Protein Synthesis and Folding:** The journey begins with the synthesis of proteins destined for membrane localization. These proteins often contain specific amino acid sequences, known as signal sequences, that guide their proper targeting. During translation, the nascent polypeptide chain emerges from the ribosome and encounters chaperones that assist in folding and preventing aggregation.

2. **Signal Recognition and Translocation:** Signal sequences, typically located at the N-terminus, are recognized by signal recognition particle (SRP), a cytosolic ribonucleoprotein complex. SRP binds to the signal sequence and the ribosome, halting translation momentarily. This complex then interacts with SRP receptor on the membrane of the endoplasmic reticulum (ER), the primary site for protein sorting and modification. This interaction triggers translocation, the movement of the nascent polypeptide chain across the ER membrane.

3. **Transmembrane Insertion:** During translocation, proteins destined for membrane localization are inserted into the membrane bilayer. This insertion process can occur through different mechanisms:
* **Type I Transmembrane Proteins:** Possess a single transmembrane domain with the N-terminus facing the lumen (inside) of the ER and the C-terminus in the cytosol.
* **Type II and III Transmembrane Proteins:** Contain a single transmembrane domain with the C-terminus (Type II) or N-terminus (Type III) facing the lumen.
* **Multipass Transmembrane Proteins:** Exhibit multiple transmembrane domains, spanning the membrane multiple times.

4. **Protein Sorting and Trafficking:** Once inserted into the ER membrane, proteins can undergo further modifications, such as glycosylation and folding, to achieve their final functional state. They are then sorted and packaged into transport vesicles, which bud from the ER and deliver their cargo to other cellular compartments, such as the Golgi apparatus, lysosomes, or the plasma membrane.

5. **Membrane Anchoring:** Proteins reaching their final destination often require specific anchoring mechanisms to maintain their association with the membrane. This can involve interactions with lipids, other proteins, or specific membrane domains.
* **Lipid Anchoring:** Some proteins are covalently linked to lipids, such as myristoylation, palmitoylation, or prenylation, which facilitate their attachment to the membrane.
* **Protein-Protein Interactions:** Other proteins associate with the membrane through interactions with transmembrane proteins or other membrane-associated proteins.
* **Specific Membrane Domains:** Proteins may target specific membrane domains, such as lipid rafts, characterized by their distinct lipid composition and protein association, which play roles in signaling and organization.

6. **Regulation and Dynamic Localization:** Membrane localization is not static but can be dynamically regulated in response to cellular signals. This dynamic nature enables cells to adapt to changing environmental conditions, coordinate cellular processes, and maintain proper function.

The intricate interplay of these stages ensures that proteins and lipids are precisely targeted and anchored to the appropriate membrane compartments, contributing to the highly organized and functional nature of cells.'"

Proteins (1)

ProteinDefinitionTaxonomy
Ras-related C3 botulinum toxin substrate 1A Ras-related C3 botulinum toxin substrate 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P63000]Homo sapiens (human)

Compounds (16)

CompoundDefinitionClassesRoles
fasudilfasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia.

fasudil: intracellular calcium antagonist; structure in first source
isoquinolines;
N-sulfonyldiazepane
antihypertensive agent;
calcium channel blocker;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
geroprotector;
neuroprotective agent;
nootropic agent;
vasodilator agent
ketorolac5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively.

ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure.

Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
amino acid;
aromatic ketone;
monocarboxylic acid;
pyrrolizines;
racemate
analgesic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
non-steroidal anti-inflammatory drug
sanguinarine chloride
chelerythrine chloride
perifosineammonium betaine;
phospholipid
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
ruboxistaurinruboxistaurin: inhibits protein kinase C beta; structure in first source
s 1033(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide
anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
sotrastaurinsotrastaurin : A member of the class of maleimides that is maleimide which is substituted at position 3 by an indol-3-yl group and at position 4 by a quinazolin-4-yl group, which in turn is substituted at position 2 by a 4-methylpiperazin-1-yl group. It is a potent and selective inhibitor of protein kinase C and has been investigated as an immunosuppresant in renal transplant patients.

sotrastaurin: a potent protein kinase C-selective inhibitor; structure in first source
indoles;
maleimides;
N-alkylpiperazine;
N-arylpiperazine;
quinazolines
anticoronaviral agent;
EC 2.7.11.13 (protein kinase C) inhibitor;
immunosuppressive agent
gdc-0973cobimetinib : A member of the class of N-acylazetidines obtained by selective formal condensation of the carboxy group of 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoic acid with the secondary amino group from the azetidine ring of 3-[(2S)-piperidin-2-yl]azetidin-3-ol. An inhibitor of mitogen-activated protein kinase that is used (as its fumarate salt) in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma.

cobimetinib: has antineoplastic activity; structure in first source
aromatic amine;
difluorobenzene;
N-acylazetidine;
organoiodine compound;
piperidines;
secondary amino compound;
tertiary alcohol
antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
azd5438sulfonamide
nsc 23766NSC 23766 trihydrochloride : A hydrochloride resulting from the formal reaction of NSC 23766 with 3 mol eq. of hydrogen chloride. An inhibitor of the signalling G-protein known as RAC1 (Ras-related C3 botulinum toxin substrate 1).

Rac1 inhibitor : Any inhibitor of Rac1.
hydrochlorideantiviral agent;
apoptosis inducer;
EC 3.6.5.2 (small monomeric GTPase) inhibitor;
muscarinic antagonist
at13148
poziotinibHM781-36B: antitumor irreversible Pan-HER inhibitor for treatment of gastric canceracrylamides;
aromatic ether;
dichlorobenzene;
diether;
monofluorobenzenes;
N-acylpiperidine;
quinazolines;
secondary amino compound;
substituted aniline
antineoplastic agent;
apoptosis inducer;
epidermal growth factor receptor antagonist
bay 869766
gilteritinibgilteritinib : A member of the class of pyrazines that is pyrazine-2-carboxamide which is substituted by {3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}nitrilo, (oxan-4-yl)nitrilo and ethyl groups at positions 3,5 and 6, respectively. It is a potent inhibitor of FLT3 and AXL tyrosine kinase receptors (IC50 = 0.29 nM and 0.73 nM, respectively). Approved by the FDA for the treatment of acute myeloid leukemia in patients who have a FLT3 gene mutation.

gilteritinib: an FLT3/AXL protein tyrosine kinase inhibitor
aromatic amine;
monomethoxybenzene;
N-methylpiperazine;
oxanes;
piperidines;
primary carboxamide;
pyrazines;
secondary amino compound
antineoplastic agent;
apoptosis inducer;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
glpg0634