Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.
-
OCTN2 transports organic cations independently of Na+ but transports carnitine only in the presence of Na+; short-chain acylcarnitines are also substrates; disease mutations M352R and P478L abolish transport.
"OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+)."
Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2.
-
hOCTN2 is an electrogenic Na+-dependent, stereoselective, high-affinity L-carnitine cotransporter (Km ~4.8 uM) that also transports betaine and is inhibited by emetine, quinidine and verapamil.
"hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+)."
L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2.
-
OCTN2 protein is present in placental brush-border (but not basal) membranes and mediates Na+-dependent, high-affinity L-carnitine uptake for maternofetal transport.
"OCTN2, a high-affinity, Na(+)-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles."
PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2.
-
The OCTN2 C-terminal PDZ-binding motif (last four residues) binds PDZK1; PDZK1 co-expression stimulates OCTN2 carnitine transport capacity ~6-fold, and the two colocalize in kidney brush-border membranes.
"The present findings are the first to identify PDZK1 as a functional regulator of OCTN2 through direct interaction with the C terminus."
OCTN2-mediated carnitine uptake in a newly discovered human proximal tubule cell line (Caki-1).
-
OCTN2 shows an apical membrane expression pattern in human proximal tubule Caki-1 cells and mediates Na+-dependent high-affinity carnitine uptake, consistent with renal tubular carnitine reabsorption.
"an apical membrane expression pattern of OCTN2 in Caki-1 cells was discovered."
OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2.
-
The functional OCTN2 is a plasma-membrane, N-glycosylated carnitine transporter; the OCTN2VT splice variant (isoform 3) is retained in the ER, poorly glycosylated, and cannot take up carnitine.
"OCTN2VT was retained in the endoplasmic reticulum (ER) with poor N-glycosylation. In addition, the retention in the ER caused no carnitine uptake into the cells."
Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+).
-
OCTN2 is a high-affinity, low-capacity transporter for butyryl-L-carnitine (electrogenic, Na+-dependent), in addition to L-carnitine.
"OCTN2 is a high-affinity/low-capacity transporter"
The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter.
-
OCTN2 is an apical intestinal organic cation transporter that takes up the B. subtilis quorum-sensing pentapeptide CSF, inducing cytoprotective heat shock proteins and contributing to intestinal homeostasis.
"These effects of CSF depend on its uptake by an apical membrane organic cation transporter-2 (OCTN2)."
Expression and localization of carnitine/organic cation transporter OCTN1 and OCTN2 in ocular epithelium.
-
OCTN2 is expressed and predominantly apically localized in human corneal and conjunctival epithelial cells, mediating apical L-carnitine uptake.
"OCTN1 and OCTN2 were predominately localized in the apical membranes of the cells."
Large-scale proteomics and phosphoproteomics of urinary exosomes.
-
Large-scale proteomic profiling of human urinary exosomes; OCTN2 is among detected renal-epithelial membrane proteins (incidental co-purification).
"Normal human urine contains large numbers of exosomes"
Cytokine regulation of OCTN2 expression and activity in small and large intestine.
-
Intestinal OCTN2 apical expression and Na+-dependent carnitine uptake are increased by IFN-gamma and TNF-alpha; siRNA knockdown confirms >80% of Na+-dependent carnitine uptake is OCTN2-dependent.
"more than 80% of Na+-dependent carnitine uptake is due to OCTN2 in Caco2BBE cells"
Transport of gabapentin by LAT1 (SLC7A5).
-
Gabapentin is transported by LAT1 (SLC7A5) at the blood-brain barrier and was negative for OCT-like transport; the abstract does not document an OCTN2 quaternary-ammonium transport assay.
"Gabapentin was negative for OCT like transport and LAT2 activity"
Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5) in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model.
-
OCTN2 siRNA knockdown dramatically suppresses Na+-dependent L-carnitine uptake in human brain endothelial cells, showing OCTN2 mediates carnitine transport at the human blood-brain barrier.
"OCTN2 is involved in L-carnitine transport at the human BBB."
Establishment and Dysfunction of the Blood-Brain Barrier.
Architecture of the human interactome defines protein communities and disease networks.
-
Proteome-scale binary interactome mapping; source of a high-throughput OCTN2 protein-binding annotation (HMGCS1) without independent functional validation.
"Architecture of the human interactome defines protein communities and disease networks"
Blood-Brain Barrier: From Physiology to Disease and Back.
A reference map of the human binary protein interactome.
-
Proteome-scale binary (Y2H) interactome map; source of high-throughput OCTN2 protein-binding annotations (keratins, KRTAP6-3, MTUS2, NOTCH2NLC) without functional validation.
"A reference map of the human binary protein interactome"
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies.
-
In deorphaning SLC22A15, OCTN2 (SLC22A5) is used as a reference zwitterion transporter; dimethylglycine is noted to interact with SLC22A5 and betaine is a known SLC22A5 substrate.
"Dimethylglycine, known to interact with SLC22A5"
Cholesterol stimulates the cellular uptake of L-carnitine by the carnitine/organic cation transporter novel 2 (OCTN2).
-
OCTN2 is responsible for cellular carnitine uptake in most tissues and resides in the plasma membrane; membrane cholesterol modulates its L-carnitine transport.
"The carnitine/organic cation transporter novel 2 (OCTN2) is responsible for the cellular uptake of carnitine in most tissues."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
-
Proteome-scale affinity-purification interactome (BioPlex); source of a high-throughput OCTN2 protein-binding annotation without functional validation.
"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome"
Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier.
-
At the human blood-testis barrier, OCTN2 localizes to Sertoli-cell basal membranes and peritubular myoid cells, consistent with a role in transport across the barrier.
"OCTN2, multidrug resistance protein (MRP) 3, MRP6, and MRP7 localized to SC basal membranes and peritubular myoid cells (PMCs)"
cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family.
-
OCTN2 is a 557-aa, 12-transmembrane organic cation transporter (chr 5q31) that mediates pH-dependent transport of tetraethylammonium and other organic cations (including neurotoxins MPP+/MPTP).
"OCTN2 mediates the transport of tetraethylammonium, a prototypical organic cation, in a pH-dependent manner."
Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2.
-
OCTN2 is a high-affinity (Km 4.34 uM), Na+-dependent human carnitine cotransporter, strongly expressed in kidney, skeletal muscle, heart and placenta.
"OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans."
Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.
-
Loss-of-function mutations in SLC22A5/OCTN2 (in jvs mice and human SCD pedigrees) abrogate carnitine transport and cause systemic primary carnitine deficiency.
"this mutation abrogates carnitine transport."
OCTN2 / SLC22A5 transports CAR from extracellular space to cytosol
SLC-mediated transport of organic cations
SLC22A4, 5,15,16 cotransport CAR, Na+ from extracellular region to cytosol
Defective SLC22A5 does not cotransport CAR, Na+ from extracellular region to cytosol