SLC22A5

UniProt ID: O76082
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

SLC22A5 (OCTN2) is a plasma-membrane, sodium-dependent, high-affinity L-carnitine transporter of the SLC22 organic cation/carnitine transporter family (major facilitator superfamily). It couples the inward movement of one sodium ion to the uptake of one molecule of (R)-carnitine (Km in the low micromolar range), mediating cellular import of carnitine from blood and diet. This uptake is the essential first step that makes carnitine available for the mitochondrial carnitine shuttle (CPT1/CACT/CPT2) and hence for long-chain fatty-acid beta-oxidation, and OCTN2 also drives renal tubular reabsorption of filtered carnitine. Beyond carnitine it is polyspecific, transporting acyl-carnitines, glycine betaine, and diverse organic cations and cationic drugs (e.g. tetraethylammonium), the latter in a lower-affinity, sodium-independent manner. It is an integral multipass membrane protein expressed at the plasma membrane, apical/brush-border in absorptive and reabsorptive epithelia (kidney proximal tubule, intestine, placenta) and at the basal membrane of Sertoli cells. Loss-of-function variants cause systemic primary carnitine deficiency, an autosomal-recessive fatty-acid oxidation disorder presenting with hypoketotic hypoglycemia, cardiomyopathy and skeletal myopathy that is treatable with oral L-carnitine.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetically-inferred plasma-membrane localization. OCTN2 is a well-established integral plasma-membrane transporter, directly demonstrated in multiple systems, so this IBA is correct and represents the site of action.
Reason: OCTN2 is an integral plasma-membrane, multipass transporter; extensive experimental evidence (below) confirms plasma-membrane localization and function.
Supporting Evidence:
PMID:33334877
The carnitine/organic cation transporter novel 2 (OCTN2) is responsible for the cellular uptake of carnitine in most tissues.
GO:0015697 quaternary ammonium group transport
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Phylogenetic inference that OCTN2 is involved in quaternary ammonium group transport. Carnitine and many OCTN2 organic-cation substrates are quaternary ammonium compounds, so this is a correct family-level process term, though broader than the specific carnitine transport that is the core function.
Reason: Correct but general; OCTN2 does transport quaternary ammonium compounds (carnitine, TEA), but the informative core process is carnitine transmembrane transport. Retained as a valid broader process.
Supporting Evidence:
PMID:10454528
OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+).
GO:0015651 quaternary ammonium group transmembrane transporter activity
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Phylogenetically-inferred quaternary ammonium group transmembrane transporter activity. OCTN2 transports quaternary ammonium substrates (carnitine, TEA), so the activity is real, but it is broader than the specific carnitine transporter activity that defines the gene.
Reason: A valid but general molecular-function term for the family; the specific core MF is carnitine transmembrane transporter activity (GO:0015226).
Supporting Evidence:
PMID:10454528
novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine.
GO:0005524 ATP binding
IEA
GO_REF:0000002
REMOVE
Summary: Electronic InterPro2GO mapping (IPR045915) assigning ATP binding. OCTN2 is a secondary active transporter that couples carnitine uptake to the sodium electrochemical gradient (Na+ symport); it is not an ATP-driven pump and there is no evidence it binds or hydrolyses ATP. This is a spurious domain-based inference.
Reason: OCTN2 is an MFS-family Na+-coupled symporter, not an ATP-binding/ATP-driven transporter. The InterPro-to-GO ATP-binding mapping is biologically incorrect for this protein; no experimental support exists.
Supporting Evidence:
PMID:10966938
hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+).
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Electronic subcellular-location mapping to endoplasmic reticulum. ER localization applies only to the non-functional splice variant OCTN2VT (isoform 3), which is retained in the ER; the functional transporter is at the plasma membrane.
Reason: ER localization is real but pertains to the ER-retained, transport-dead isoform 3 (OCTN2VT); it is not the location of the functional carnitine transporter. Retained as a non-core, isoform-restricted annotation.
Supporting Evidence:
PMID:17509700
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.
GO:0005886 plasma membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Electronic subcellular-location mapping to plasma membrane, consistent with the well-established localization of the functional transporter.
Reason: Correctly captures the plasma-membrane localization of OCTN2, confirmed experimentally.
Supporting Evidence:
PMID:33334877
OCTN2 must interact with the surrounding lipid microenvironment to function.
GO:0009925 basal plasma membrane
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Electronic annotation of basal plasma membrane localization. OCTN2 is predominantly apical/brush-border in most epithelia but is localized to the basal membrane of Sertoli cells, so a basal-membrane annotation is supportable in specific cell types.
Reason: Cell-type-specific basal localization (Sertoli cells) is documented; not the predominant (apical) localization, so kept as non-core.
Supporting Evidence:
PMID:35307651
OCTN2, multidrug resistance protein (MRP) 3, MRP6, and MRP7 localized to SC basal membranes and peritubular myoid cells (PMCs)
GO:0015199 amino-acid betaine transmembrane transporter activity
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Electronic (ARBA) annotation of amino-acid betaine transmembrane transporter activity. OCTN2 does transport glycine betaine, so this is correct; it is a secondary substrate rather than the core carnitine activity.
Reason: OCTN2-mediated betaine transport is experimentally documented; a genuine but non-core polyspecific activity.
Supporting Evidence:
PMID:10966938
hOCTN2 mediated transport of betaine.
GO:0015837 amine transport
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Electronic (ARBA) annotation to the broad process amine transport. OCTN2 transports amine-containing organic cations and carnitine, so this is correct but very general.
Reason: A correct but broad parent process; the specific process is carnitine transmembrane transport.
Supporting Evidence:
PMID:10454528
OCTN2 transports organic cations without involving Na(+)
GO:0015879 carnitine transport
IEA
GO_REF:0000002
ACCEPT
Summary: Electronic InterPro2GO annotation to carnitine transport, matching the defining physiological role of OCTN2.
Reason: Carnitine transport is the core biological process of OCTN2, extensively documented experimentally.
Supporting Evidence:
PMID:9685390
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
GO:0016020 membrane
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Electronic InterPro annotation to the generic term membrane. Correct (OCTN2 is a multipass membrane protein) but uninformative relative to the specific plasma-membrane annotations.
Reason: Trivially correct generic location; superseded by the more specific plasma-membrane annotations.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:0016324 apical plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic annotation of apical plasma membrane localization, consistent with the polarized apical/brush-border localization of OCTN2 in epithelia.
Reason: Apical localization is directly documented in kidney, intestine, placenta and ocular epithelia; correct.
Supporting Evidence:
PMID:17274673
an apical membrane expression pattern of OCTN2 in Caki-1 cells was discovered.
GO:0022857 transmembrane transporter activity
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Electronic InterPro annotation to the root transmembrane transporter activity term. Correct but maximally general.
Reason: Trivially correct high-level MF; the informative MF is carnitine transmembrane transporter activity.
Supporting Evidence:
PMID:9685390
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
GO:0030165 PDZ domain binding
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Electronic (ARBA) annotation of PDZ domain binding. OCTN2 has a C-terminal PDZ-binding motif that binds the PDZ protein PDZK1, which regulates its transport activity; this is experimentally confirmed (see PMID:15523054 IPI annotation below).
Reason: PDZ-domain binding (via the C-terminal motif, to PDZK1) is real and functionally relevant to OCTN2 regulation, but is an accessory regulatory interaction rather than the transporter's core function.
Supporting Evidence:
PMID:15523054
a requirement of the last four amino acids in OCTN1 and OCTN2 for the interaction
GO:0055085 transmembrane transport
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Electronic InterPro annotation to the broad process transmembrane transport. Correct but general.
Reason: Correct high-level process; superseded by carnitine transmembrane transport.
Supporting Evidence:
PMID:9685390
uptake of L-[3H]carnitine was strongly enhanced in a sodium-dependent manner
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
MARK AS OVER ANNOTATED
Summary: High-throughput interactome (HuRI/CCSB) interaction, here with HMGCS1. Bare protein binding is uninformative about molecular function and this HT-derived binary interaction has no independent functional validation for OCTN2.
Reason: Generic protein binding from a proteome-scale interactome screen; provides no functional insight and the specific interaction (HMGCS1) is not biologically characterized for OCTN2. Per curation guidelines, bare protein binding is not retained as informative.
Supporting Evidence:
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: High-throughput binary interactome (HuRI) interactions (with keratins KRT34, KRTAP6-3, MTUS2, NOTCH2NLC and others). Bare protein binding from a large-scale Y2H map, uninformative about OCTN2 molecular function.
Reason: Generic protein binding from a proteome-scale interactome map; keratin/keratin- associated-protein partners are common Y2H artifacts and are not biologically validated for OCTN2. Not informative of function.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
MARK AS OVER ANNOTATED
Summary: High-throughput proteome-scale interactome (BioPlex) interaction, here with HMGCS1. Bare protein binding, uninformative about molecular function.
Reason: Generic protein binding from a proteome-scale affinity-purification map; no functional characterization for OCTN2. Not retained as informative.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0015837 amine transport
TAS
Reactome:R-HSA-549127
KEEP AS NON CORE
Summary: Reactome-asserted involvement in the broad process amine transport (SLC-mediated transport of organic cations). Correct but general; the specific OCTN2 process is carnitine transmembrane transport.
Reason: Reactome pathway assertion for a general amine/organic-cation transport process; correct but broader than the specific carnitine function.
Supporting Evidence:
PMID:10454528
OCTN2 transports organic cations without involving Na(+)
GO:1902603 carnitine transmembrane transport
TAS
Reactome:R-HSA-165026
ACCEPT
Summary: Reactome-asserted involvement in carnitine transmembrane transport (OCTN2 transports carnitine from extracellular space to cytosol). This is the core biological process of OCTN2.
Reason: Directly captures the defining process; supported by Reactome and by extensive experimental evidence.
Supporting Evidence:
PMID:9685390
uptake of L-[3H]carnitine was strongly enhanced in a sodium-dependent manner
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:15238359
L-Carnitine transport in human placental brush-border membra...
ACCEPT
Summary: Direct assay of OCTN2-mediated Na+-dependent, high-affinity L-carnitine transport in human placental brush-border membranes. This is the core molecular function of OCTN2.
Reason: Experimentally demonstrated carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:15238359
OCTN2, a high-affinity, Na(+)-dependent carnitine transporter, was present in placental BBM
GO:1902603 carnitine transmembrane transport
IDA
PMID:15238359
L-Carnitine transport in human placental brush-border membra...
ACCEPT
Summary: Direct evidence that OCTN2 mediates L-carnitine transport across the placental brush-border membrane. Core biological process.
Reason: Experimentally demonstrated carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:15238359
l-carnitine uptake was sodium and temperature dependent, showed high affinity for carnitine
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:15523054
PDZK1 directly regulates the function of organic cation/carn...
ACCEPT
Summary: OCTN2-mediated carnitine uptake measured directly (and shown to be stimulated ~6-fold by PDZK1 co-expression). Confirms carnitine transporter activity.
Reason: Direct assay of OCTN2 carnitine transport activity; core molecular function.
Supporting Evidence:
PMID:15523054
double transfection of OCTN2 with PDZK1 stimulated the uptake by OCTN2 of its endogenous substrate carnitine
GO:1902603 carnitine transmembrane transport
IDA
PMID:15523054
PDZK1 directly regulates the function of organic cation/carn...
ACCEPT
Summary: Direct evidence of OCTN2-mediated carnitine transport (endogenous substrate carnitine), core biological process.
Reason: Experimentally demonstrated carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:15523054
the uptake by OCTN2 of its endogenous substrate carnitine
GO:0005783 endoplasmic reticulum
EXP
PMID:17509700
OCTN2VT, a splice variant of OCTN2, does not transport carni...
KEEP AS NON CORE
Summary: Experimental demonstration of ER localization for the OCTN2VT splice variant (isoform 3), which is ER-retained and unable to transport carnitine. This is an isoform-specific, non-functional location.
Reason: ER localization is genuine but restricted to the transport-dead isoform 3 (OCTN2VT); it does not describe the functional transporter's location. Kept as isoform-specific non-core.
Supporting Evidence:
PMID:17509700
OCTN2VT was retained in the endoplasmic reticulum (ER) with poor N-glycosylation.
GO:0005886 plasma membrane
EXP
PMID:33334877
Cholesterol stimulates the cellular uptake of L-carnitine by...
ACCEPT
Summary: Experimental plasma-membrane localization of functional OCTN2 (HEK293 cells overexpressing OCTN2; cholesterol modulation studies). Core localization.
Reason: Directly documented plasma-membrane localization of the active transporter.
Supporting Evidence:
PMID:33334877
how plasma membrane cholesterol modulates OCTN2 transport of L-carnitine
GO:0016324 apical plasma membrane
EXP
PMID:10966938
Functional and pharmacological characterization of human Na(...
ACCEPT
Summary: Functional/pharmacological characterization of hOCTN2 as an electrogenic Na+-carnitine cotransporter; UniProt records apical cell-membrane localization from this work. Apical localization is well-supported across epithelia.
Reason: Apical plasma-membrane localization of OCTN2 is documented here and in multiple epithelial systems; correct.
Supporting Evidence:
PMID:10966938
hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+).
GO:0015199 amino-acid betaine transmembrane transporter activity
IDA
PMID:33124720
Deorphaning a solute carrier 22 family member, SLC22A15, thr...
KEEP AS NON CORE
Summary: OCTN2 is used here as a reference zwitterion transporter and its betaine/dimethylglycine transport is noted; UniProt records betaine and N,N-dimethylglycine as OCTN2 substrates. Betaine transport by OCTN2 was demonstrated experimentally in PMID:10966938.
Reason: OCTN2-mediated betaine (and dimethylglycine) transport is a genuine but secondary polyspecific activity; not the core carnitine function.
Supporting Evidence:
PMID:33124720
Dimethylglycine, known to interact with SLC22A5
PMID:10966938
hOCTN2 mediated transport of betaine.
GO:0034341 response to type II interferon
IDA
PMID:20722056
Cytokine regulation of OCTN2 expression and activity in smal...
KEEP AS NON CORE
Summary: Intestinal OCTN2 expression and Na+-dependent carnitine uptake activity are increased by IFN-gamma. This is a regulatory response (OCTN2 is induced by the cytokine), not a core transporter function.
Reason: OCTN2 responds to (is induced by) IFN-gamma in intestine; a genuine but peripheral/regulatory biological process rather than the transporter's core function.
Supporting Evidence:
PMID:20722056
IFN-Ξ³ increased both total and apical membrane expression of Caco2BBE OCTN2
GO:0034612 response to tumor necrosis factor
IDA
PMID:20722056
Cytokine regulation of OCTN2 expression and activity in smal...
KEEP AS NON CORE
Summary: Intestinal OCTN2 apical membrane expression and carnitine uptake are increased by TNF-alpha. A regulatory/response process, not core transport function.
Reason: OCTN2 responds to (is regulated by) TNF; peripheral regulatory process.
Supporting Evidence:
PMID:20722056
TNF-Ξ± stimulated apical expression
GO:1900749 (R)-carnitine transport
IDA
PMID:20722056
Cytokine regulation of OCTN2 expression and activity in smal...
ACCEPT
Summary: Na+-dependent 3H-carnitine uptake by OCTN2 measured directly in intestinal epithelial cells (siRNA-confirmed as OCTN2-dependent). Core carnitine transport process.
Reason: Directly demonstrated OCTN2-mediated (R)-carnitine transport; core process.
Supporting Evidence:
PMID:20722056
more than 80% of Na+-dependent carnitine uptake is due to OCTN2 in Caco2BBE cells
GO:1901235 (R)-carnitine transmembrane transporter activity
IDA
PMID:20722056
Cytokine regulation of OCTN2 expression and activity in smal...
ACCEPT
Summary: OCTN2-mediated Na+-dependent (R)-carnitine transporter activity demonstrated directly (siRNA knockdown abolishes >80% of Na+-dependent uptake). Core molecular function at the specific substrate level.
Reason: Direct evidence of (R)-carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:20722056
The Na+-dependent 3H-carnitine uptake in cells treated with OCTN2 siRNA was reduced from 0.88 Β± 0.10 to 0.16 Β± 0.06
GO:0009925 basal plasma membrane
IDA
PMID:35307651
Localization of Xenobiotic Transporters Expressed at the Hum...
KEEP AS NON CORE
Summary: Immunohistological localization of OCTN2 to Sertoli-cell basal membranes and peritubular myoid cells at the human blood-testis barrier. Cell-type-specific basal localization.
Reason: Documented basal-membrane localization in specific testicular cell types; not the predominant apical localization, so non-core.
Supporting Evidence:
PMID:35307651
OCTN2, multidrug resistance protein (MRP) 3, MRP6, and MRP7 localized to SC basal membranes and peritubular myoid cells (PMCs)
GO:0005886 plasma membrane
IDA
PMID:17509700
OCTN2VT, a splice variant of OCTN2, does not transport carni...
ACCEPT
Summary: Functional OCTN2 shown at the plasma membrane (with robust N-glycosylation), contrasted with the ER-retained OCTN2VT variant. Core localization.
Reason: Direct plasma-membrane localization of the functional transporter.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:0016324 apical plasma membrane
IDA
PMID:18005709
The Bacillus subtilis quorum-sensing molecule CSF contribute...
ACCEPT
Summary: OCTN2 identified as an apical membrane organic cation transporter in intestinal epithelial cells, mediating uptake of the bacterial CSF pentapeptide. Apical localization is the site of action in absorptive epithelia.
Reason: Apical plasma-membrane site of action directly demonstrated in intestinal epithelia.
Supporting Evidence:
PMID:18005709
These effects of CSF depend on its uptake by an apical membrane organic cation transporter-2 (OCTN2).
GO:0016324 apical plasma membrane
IDA
PMID:20722056
Cytokine regulation of OCTN2 expression and activity in smal...
ACCEPT
Summary: OCTN2 localized to the apical (brush-border) membrane of intestinal epithelial cells by immunohistochemistry and surface biotinylation. Core polarized localization.
Reason: Directly documented apical plasma-membrane localization in intestine.
Supporting Evidence:
PMID:20722056
OCTN2 was highly expressed in the brush border (apical membrane) and subapical region of epithelial cells
GO:0022857 transmembrane transporter activity
IDA
PMID:18005709
The Bacillus subtilis quorum-sensing molecule CSF contribute...
KEEP AS NON CORE
Summary: OCTN2 demonstrated to transport the bacterial CSF pentapeptide across the apical membrane. This supports transmembrane transporter activity, though the annotation uses the maximally general MF term.
Reason: Correct but general MF; the specific informative MF is carnitine transmembrane transporter activity. Retained as a valid broader term.
Supporting Evidence:
PMID:18005709
OCTN2-mediated CSF transport serves as an example of a host-bacterial interaction
GO:0070715 sodium-dependent organic cation transport
IDA
PMID:18005709
The Bacillus subtilis quorum-sensing molecule CSF contribute...
KEEP AS NON CORE
Summary: OCTN2-mediated apical uptake of the cationic bacterial pentapeptide CSF; UniProt records this as a Na+-coupled transport reaction. Supports Na+-dependent organic cation (peptide) transport.
Reason: A genuine polyspecific Na+-dependent organic-cation transport activity (CSF peptide), distinct from the core carnitine function; retained as non-core.
Supporting Evidence:
PMID:18005709
These effects of CSF depend on its uptake by an apical membrane organic cation transporter-2 (OCTN2).
GO:1900749 (R)-carnitine transport
IDA
PMID:17509700
OCTN2VT, a splice variant of OCTN2, does not transport carni...
ACCEPT
Summary: OCTN2 shown to be indispensable for carnitine transport across the plasma membrane (the functional variant transports carnitine, the ER-retained variant does not). Core carnitine transport process.
Reason: Direct evidence for OCTN2-mediated (R)-carnitine transport; core process.
Supporting Evidence:
PMID:17509700
A novel organic cation transporter OCTN2 is indispensable for carnitine transport across plasma membrane
GO:1900749 (R)-carnitine transport
IDA
PMID:33334877
Cholesterol stimulates the cellular uptake of L-carnitine by...
ACCEPT
Summary: OCTN2 responsible for cellular uptake of carnitine; carnitine transport measured directly in OCTN2-overexpressing cells (and shown to be cholesterol- dependent). Core carnitine transport process.
Reason: Direct evidence for OCTN2-mediated carnitine uptake; core process.
Supporting Evidence:
PMID:33334877
The carnitine/organic cation transporter novel 2 (OCTN2) is responsible for the cellular uptake of carnitine in most tissues.
GO:1901235 (R)-carnitine transmembrane transporter activity
IDA
PMID:17509700
OCTN2VT, a splice variant of OCTN2, does not transport carni...
ACCEPT
Summary: OCTN2 (functional isoform) transports carnitine across the plasma membrane; the ER-retained OCTN2VT does not, confirming that plasma-membrane OCTN2 is the carnitine transporter. Core molecular function.
Reason: Direct evidence for (R)-carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:17509700
the retention in the ER caused no carnitine uptake into the cells
GO:1901235 (R)-carnitine transmembrane transporter activity
IDA
PMID:33334877
Cholesterol stimulates the cellular uptake of L-carnitine by...
ACCEPT
Summary: Direct carnitine transport assays in OCTN2-overexpressing HEK293 cells establish OCTN2 (R)-carnitine transporter activity (modulated by membrane cholesterol). Core molecular function.
Reason: Direct evidence for (R)-carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:33334877
how plasma membrane cholesterol modulates OCTN2 transport of L-carnitine
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:10454528
Functional characteristics and tissue distribution pattern o...
ACCEPT
Summary: Functional characterization establishing OCTN2 as a Na+-dependent carnitine transporter (and Na+-independent organic cation transporter). Core molecular function.
Reason: Direct experimental demonstration of carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:10454528
it transports carnitine only in the presence of Na(+)
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:10966938
Functional and pharmacological characterization of human Na(...
ACCEPT
Summary: Electrophysiological and flux characterization of hOCTN2 as an electrogenic Na+-carnitine cotransporter (Km ~4.8 uM). Core molecular function.
Reason: Direct evidence for high-affinity carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:10966938
hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+).
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:17855766
Transport of butyryl-L-carnitine, a potential prodrug, via t...
ACCEPT
Summary: OCTN2 transports L-carnitine and its butyryl ester (butyryl-L-carnitine) as a high-affinity transporter. Confirms carnitine transporter activity.
Reason: Direct evidence of OCTN2 carnitine (and acyl-carnitine) transport activity; core molecular function.
Supporting Evidence:
PMID:17855766
OCTN2 is a high-affinity/low-capacity transporter
GO:0015651 quaternary ammonium group transmembrane transporter activity
IMP
PMID:10454528
Functional characteristics and tissue distribution pattern o...
KEEP AS NON CORE
Summary: OCTN2 transports quaternary ammonium substrates (carnitine, organic cations); loss-of-function mutants (M352R, P478L) abolish transport. Correct family-level MF, broader than the specific carnitine activity.
Reason: A correct but general quaternary ammonium transporter activity; the specific core MF is carnitine transmembrane transporter activity.
Supporting Evidence:
PMID:10454528
Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function
GO:0015651 quaternary ammonium group transmembrane transporter activity
IMP
PMID:10966938
Functional and pharmacological characterization of human Na(...
KEEP AS NON CORE
Summary: hOCTN2 transports carnitine and betaine (quaternary ammonium compounds); shows only small currents with classic OCT substrates. Correct but general MF.
Reason: Correct family-level quaternary-ammonium MF; superseded by the specific carnitine transporter activity as the core function.
Supporting Evidence:
PMID:10966938
hOCTN2 mediated transport of betaine.
GO:0015697 quaternary ammonium group transport
IMP
PMID:10454528
Functional characteristics and tissue distribution pattern o...
KEEP AS NON CORE
Summary: OCTN2 mediates transport of quaternary ammonium compounds (carnitine and organic cations); mutation studies confirm transport function. Correct but broad process.
Reason: Correct but general process; the specific process is carnitine transmembrane transport.
Supporting Evidence:
PMID:10454528
OCTN2 transports organic cations without involving Na(+)
GO:0015697 quaternary ammonium group transport
IMP
PMID:10966938
Functional and pharmacological characterization of human Na(...
KEEP AS NON CORE
Summary: hOCTN2 transports the quaternary ammonium compounds carnitine and betaine. Correct but broad process term.
Reason: Correct general process; superseded by carnitine transmembrane transport.
Supporting Evidence:
PMID:10966938
hOCTN2 mediated transport of betaine.
GO:1902270 (R)-carnitine transmembrane transport
IDA
PMID:10454528
Functional characteristics and tissue distribution pattern o...
ACCEPT
Summary: Direct demonstration that OCTN2 transports carnitine (Na+-dependently) across the membrane. Core carnitine transport process at the specific substrate level.
Reason: Direct evidence for (R)-carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:10454528
it transports carnitine only in the presence of Na(+)
GO:1902270 (R)-carnitine transmembrane transport
IDA
PMID:10966938
Functional and pharmacological characterization of human Na(...
ACCEPT
Summary: Electrogenic Na+-dependent L-carnitine transport by hOCTN2 characterized by voltage clamp/flux. Core carnitine transport process.
Reason: Direct evidence for (R)-carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:10966938
L-carnitine transport was electrogenic.
GO:1902270 (R)-carnitine transmembrane transport
IDA
PMID:17855766
Transport of butyryl-L-carnitine, a potential prodrug, via t...
ACCEPT
Summary: OCTN2 transports L-carnitine (and butyryl-L-carnitine) in an electrogenic, Na+-dependent manner. Core carnitine transport process.
Reason: Direct evidence for (R)-carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:17855766
Transport of BC via OCTN2 is electrogenic
GO:1901235 (R)-carnitine transmembrane transporter activity
IMP
PMID:23877104
Functional expression of organic cation/carnitine transporte...
ACCEPT
Summary: OCTN2 gene silencing dramatically suppresses Na+-dependent L-carnitine uptake in human brain capillary endothelial cells, demonstrating OCTN2 (R)-carnitine transporter activity. Core molecular function.
Reason: siRNA knockdown directly implicates OCTN2 in (R)-carnitine transporter activity; core molecular function.
Supporting Evidence:
PMID:23877104
[(3)H]L-Carnitine uptake was dramatically suppressed by silencing of the OCTN2 gene.
GO:0005737 cytoplasm
ISS
GO_REF:0000024
REMOVE
Summary: Sequence-similarity transfer (from mouse Octn2, O70594) of a cytoplasm annotation. OCTN2 is an integral multipass plasma-membrane transporter; a bulk cytoplasm localization does not describe its functional location and is a likely mislocalization/over-annotation.
Reason: OCTN2 is an integral membrane protein resident in the plasma membrane (and ER for the non-functional isoform); a generic cytoplasm location is not supported and is misleading. This ISS is an over-annotation.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:1901235 (R)-carnitine transmembrane transporter activity
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity transfer (from mouse Octn2) of (R)-carnitine transporter activity. Consistent with the directly demonstrated human OCTN2 function.
Reason: ISS from mouse ortholog matches the extensive direct human evidence for (R)-carnitine transmembrane transporter activity; core molecular function.
Supporting Evidence:
PMID:10966938
high-affinity transport of L-carnitine and Na(+).
GO:1902270 (R)-carnitine transmembrane transport
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity transfer (from mouse Octn2) of (R)-carnitine transmembrane transport. Consistent with the directly demonstrated human process.
Reason: ISS matches abundant direct human evidence for (R)-carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:10454528
it transports carnitine only in the presence of Na(+)
GO:0015226 carnitine transmembrane transporter activity
EXP
PMID:9685390
Molecular and functional identification of sodium ion-depend...
ACCEPT
Summary: Original molecular/functional identification of OCTN2 as a high-affinity, Na+-dependent carnitine transporter (Km 4.34 uM). Foundational evidence for the core molecular function.
Reason: Direct experimental identification of OCTN2 carnitine transporter activity; core molecular function.
Supporting Evidence:
PMID:9685390
uptake of L-[3H]carnitine was strongly enhanced in a sodium-dependent manner with Km value of 4.34 microM
GO:0015226 carnitine transmembrane transporter activity
TAS
Reactome:R-HSA-549297
ACCEPT
Summary: Reactome assertion that SLC22A5 (with SLC22A4/15/16) cotransports carnitine and Na+ from extracellular region to cytosol. Core molecular function.
Reason: Reactome pathway assertion matching the well-established core carnitine transporter activity.
Supporting Evidence:
PMID:9685390
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
GO:0015226 carnitine transmembrane transporter activity
TAS
Reactome:R-HSA-5625674
ACCEPT
Summary: Reactome assertion (defective SLC22A5 does not cotransport carnitine/Na+) referencing the normal carnitine transporter activity of OCTN2. Core molecular function.
Reason: Reactome pathway assertion consistent with the established core carnitine transporter activity (and its loss in disease).
Supporting Evidence:
PMID:9916797
loss of OCTN2 function causes SCD
GO:0005829 cytosol
ISS
GO_REF:0000024
REMOVE
Summary: Sequence-similarity transfer (from mouse Octn2) of a cytosol annotation. As with the cytoplasm annotation, OCTN2 is an integral plasma-membrane protein; a cytosol localization is not supported.
Reason: OCTN2 is an integral membrane transporter, not a cytosolic/soluble protein; the ISS cytosol annotation is a mislocalization/over-annotation.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:0005886 plasma membrane
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity transfer (from mouse Octn2) of plasma-membrane localization, consistent with the direct human evidence. Core localization.
Reason: ISS matches abundant direct evidence for plasma-membrane localization of OCTN2.
Supporting Evidence:
PMID:33334877
OCTN2 must interact with the surrounding lipid microenvironment to function.
GO:0150104 transport across blood-brain barrier
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Sequence-similarity transfer (from rat Octn2, Q9Z0E8) of a role in transport across the blood-brain barrier. OCTN2 is functionally expressed at the human BBB and mediates L-carnitine uptake there (confirmed by siRNA in PMID:23877104).
Reason: OCTN2 contributes to carnitine transport at the blood-brain barrier, a tissue-specific manifestation of its core carnitine transport function rather than a distinct core process.
Supporting Evidence:
PMID:23877104
OCTN2 is involved in L-carnitine transport at the human BBB.
GO:1902270 (R)-carnitine transmembrane transport
IMP
PMID:23877104
Functional expression of organic cation/carnitine transporte...
ACCEPT
Summary: OCTN2 gene silencing suppresses Na+-dependent L-carnitine uptake in human brain endothelial cells, implicating OCTN2 in (R)-carnitine transmembrane transport. Core carnitine transport process.
Reason: siRNA knockdown directly implicates OCTN2 in (R)-carnitine transmembrane transport; core process.
Supporting Evidence:
PMID:23877104
[(3)H]L-Carnitine uptake was dramatically suppressed by silencing of the OCTN2 gene.
GO:0015651 quaternary ammonium group transmembrane transporter activity
IDA
PMID:23567998
Transport of gabapentin by LAT1 (SLC7A5).
UNDECIDED
Summary: This paper concerns gabapentin transport by LAT1 (SLC7A5) at the blood-brain barrier; its abstract characterizes LAT1 and reports that gabapentin was negative for OCT-like transport. The cached abstract does not document an OCTN2/quaternary-ammonium transport assay, and the full text is unavailable, so the basis of the ARUK-UCL IDA annotation to OCTN2 cannot be verified from the cache.
Reason: Cannot verify the OCTN2-specific supporting evidence from the abstract-only cache (the paper foregrounds LAT1); per curation policy, an experimental annotation whose full text I cannot read is left UNDECIDED rather than removed.
Supporting Evidence:
PMID:23567998
Gabapentin was negative for OCT like transport and LAT2 activity
GO:0015697 quaternary ammonium group transport
IDA
PMID:23567998
Transport of gabapentin by LAT1 (SLC7A5).
UNDECIDED
Summary: As above (PMID:23567998, gabapentin/LAT1). The cached abstract does not document an OCTN2 quaternary-ammonium transport assay; full text unavailable.
Reason: The OCTN2-specific evidence cannot be verified from the abstract-only cache; left UNDECIDED rather than removed per policy on experimental annotations.
Supporting Evidence:
PMID:23567998
Gabapentin was negative for OCT like transport and LAT2 activity
GO:0150104 transport across blood-brain barrier
NAS
PMID:30280653
Blood-Brain Barrier: From Physiology to Disease and Back.
KEEP AS NON CORE
Summary: Non-traceable author-statement annotation citing a general blood-brain- barrier review. The specific functional evidence for OCTN2 at the BBB comes from the experimental PMID:23877104; this NAS from a review is weak support.
Reason: A weak (NAS, from a review) restatement of OCTN2's tissue-specific BBB carnitine-transport role; kept as non-core, with the experimental evidence provided by PMID:23877104.
Supporting Evidence:
PMID:23877104
OCTN2 is involved in L-carnitine transport at the human BBB.
GO:0150104 transport across blood-brain barrier
NAS
PMID:26590417
Establishment and Dysfunction of the Blood-Brain Barrier.
KEEP AS NON CORE
Summary: Non-traceable author-statement annotation citing a general blood-brain- barrier review. Weak support; the functional OCTN2 BBB evidence is experimental (PMID:23877104).
Reason: Weak (NAS, review-based) restatement of the tissue-specific BBB carnitine- transport role; non-core.
Supporting Evidence:
PMID:23877104
OCTN2 is involved in L-carnitine transport at the human BBB.
GO:0009609 response to symbiotic bacterium
IMP
PMID:18005709
The Bacillus subtilis quorum-sensing molecule CSF contribute...
KEEP AS NON CORE
Summary: OCTN2-dependent uptake of the Bacillus subtilis quorum-sensing peptide CSF in intestinal epithelia links the transporter to host responses to commensal bacteria. A downstream, tissue-specific biology of OCTN2's cationic- peptide transport, not a core transporter function.
Reason: Genuine but peripheral role (mediating uptake of a bacterial signaling peptide) downstream of OCTN2's transport activity; non-core.
Supporting Evidence:
PMID:18005709
OCTN2-mediated CSF transport serves as an example of a host-bacterial interaction that allows the host to monitor and respond to changes in the behavior or composition of colonic flora.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5625674
ACCEPT
Summary: Reactome-asserted plasma-membrane localization of SLC22A5. Consistent with the established core localization.
Reason: Reactome pathway assertion matching well-established plasma-membrane localization.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
MARK AS OVER ANNOTATED
Summary: High-throughput proteomic detection of OCTN2 among proteins in human urinary exosomes. Incidental proteomic co-purification (renal epithelial membrane proteins are commonly recovered in urinary exosomes); not a functional subcellular location.
Reason: Exosome detection is a mass-spectrometry co-occurrence consistent with shedding of apical renal membrane proteins; it does not indicate a functional exosomal role and over-annotates the localization.
Supporting Evidence:
PMID:19056867
Normal human urine contains large numbers of exosomes
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-165026
ACCEPT
Summary: Reactome-asserted plasma-membrane localization of SLC22A5 (in the carnitine transport reaction). Consistent with core localization.
Reason: Reactome assertion matching established plasma-membrane localization.
Supporting Evidence:
PMID:33334877
OCTN2 must interact with the surrounding lipid microenvironment to function.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-549297
ACCEPT
Summary: Reactome-asserted plasma-membrane localization of SLC22A5 (in the carnitine/Na+ cotransport reaction). Consistent with core localization.
Reason: Reactome assertion matching established plasma-membrane localization.
Supporting Evidence:
PMID:17509700
OCTN2 was expressed on the plasma membrane with robust N-glycosylation
GO:0060731 positive regulation of intestinal epithelial structure maintenance
IMP
PMID:18005709
The Bacillus subtilis quorum-sensing molecule CSF contribute...
KEEP AS NON CORE
Summary: OCTN2-mediated uptake of the bacterial CSF peptide induces cytoprotective heat shock proteins that prevent oxidant-induced intestinal epithelial injury and loss of barrier function, linking OCTN2 to intestinal homeostasis. A downstream, tissue-specific process rather than a core transporter function.
Reason: Genuine but peripheral physiological consequence of OCTN2 cationic-peptide transport in the intestine; non-core.
Supporting Evidence:
PMID:18005709
CSF also induces cytoprotective heat shock proteins (Hsps), which prevent oxidant-induced intestinal epithelial cell injury and loss of barrier function.
GO:0070715 sodium-dependent organic cation transport
IDA
PMID:15238359
L-Carnitine transport in human placental brush-border membra...
ACCEPT
Summary: OCTN2-mediated Na+-dependent, high-affinity L-carnitine uptake in placental brush-border membranes. Carnitine is a zwitterionic organic cation; this Na+-dependent organic-cation transport is essentially the core carnitine uptake function.
Reason: Directly demonstrated Na+-dependent organic-cation (carnitine) transport by OCTN2; reflects the core function.
Supporting Evidence:
PMID:15238359
l-carnitine uptake was sodium and temperature dependent
GO:0070715 sodium-dependent organic cation transport
IDA
PMID:9685390
Molecular and functional identification of sodium ion-depend...
ACCEPT
Summary: OCTN2 characterized as a sodium-dependent high-affinity carnitine (zwitterionic organic cation) transporter. Reflects the core Na+-coupled transport mechanism.
Reason: Directly demonstrated Na+-dependent organic-cation (carnitine) transport; reflects the core function/mechanism.
Supporting Evidence:
PMID:9685390
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
GO:0005515 protein binding
IPI
PMID:15523054
PDZK1 directly regulates the function of organic cation/carn...
MARK AS OVER ANNOTATED
Summary: OCTN2 binds the PDZ scaffolding protein PDZK1 (interaction data). While recorded as generic protein binding, this specific interaction is functionally important (PDZK1 stimulates OCTN2 carnitine transport). The informative capture is the PDZ-domain-binding annotation (GO:0030165) from the same study.
Reason: Bare protein binding is uninformative per curation guidelines; the biologically meaningful content (binding PDZK1 via a PDZ motif) is better captured by the PDZ domain binding annotation from the same reference.
Supporting Evidence:
PMID:15523054
The present findings are the first to identify PDZK1 as a functional regulator of OCTN2 through direct interaction with the C terminus.
GO:0005886 plasma membrane
IC
PMID:9618255
cDNA sequence, transport function, and genomic organization ...
ACCEPT
Summary: Plasma-membrane localization inferred by the curator from the demonstrated transport function (OCTN2 mediates TEA transport when expressed in HeLa cells). Consistent with the established core localization.
Reason: Plasma-membrane localization inferred from surface transport function and confirmed by later direct evidence; correct.
Supporting Evidence:
PMID:9618255
OCTN2 mediates the transport of tetraethylammonium, a prototypical organic cation, in a pH-dependent manner.
GO:0015226 carnitine transmembrane transporter activity
IDA
PMID:9685390
Molecular and functional identification of sodium ion-depend...
ACCEPT
Summary: Original identification of OCTN2 as a high-affinity Na+-dependent carnitine transporter. Core molecular function.
Reason: Direct experimental demonstration of carnitine transporter activity; core molecular function.
Supporting Evidence:
PMID:9685390
uptake of L-[3H]carnitine was strongly enhanced in a sodium-dependent manner with Km value of 4.34 microM
GO:0015226 carnitine transmembrane transporter activity
IMP
PMID:9916797
Primary systemic carnitine deficiency is caused by mutations...
ACCEPT
Summary: Mutational evidence that loss of OCTN2 function causes systemic carnitine deficiency (jvs mouse mutation abrogates carnitine transport; human SLC22A5 mutations in SCD pedigrees). Confirms OCTN2 carnitine transporter activity via loss-of-function. Core molecular function.
Reason: Loss-of-function (disease/mutation) evidence directly supports carnitine transporter activity; core molecular function.
Supporting Evidence:
PMID:9916797
this mutation abrogates carnitine transport.
GO:0015651 quaternary ammonium group transmembrane transporter activity
IDA
PMID:9618255
cDNA sequence, transport function, and genomic organization ...
KEEP AS NON CORE
Summary: OCTN2 mediates transport of the quaternary ammonium compound tetraethylammonium (TEA) in a pH-dependent manner when expressed in HeLa cells. Correct family-level MF, broader than the specific carnitine activity.
Reason: Genuine quaternary-ammonium (organic cation) transporter activity, but the informative core MF is carnitine transmembrane transporter activity.
Supporting Evidence:
PMID:9618255
OCTN2 mediates the transport of tetraethylammonium, a prototypical organic cation, in a pH-dependent manner.
GO:0015697 quaternary ammonium group transport
IDA
PMID:9618255
cDNA sequence, transport function, and genomic organization ...
KEEP AS NON CORE
Summary: OCTN2 transports the quaternary ammonium organic cation TEA (and competing organic cations MPP+, MPTP, methamphetamine). Correct but broad process.
Reason: Correct but general organic-cation transport process; the specific process is carnitine transmembrane transport.
Supporting Evidence:
PMID:9618255
Several organic cations, including the neurotoxins 1-methyl-4-phenylpyridinium
GO:0015879 carnitine transport
IDA
PMID:9685390
Molecular and functional identification of sodium ion-depend...
ACCEPT
Summary: OCTN2 identified as the physiologically important high-affinity Na+-carnitine cotransporter. Core carnitine transport process.
Reason: Direct evidence of OCTN2-mediated carnitine transport; core process.
Supporting Evidence:
PMID:9685390
OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
GO:0015879 carnitine transport
IMP
PMID:9916797
Primary systemic carnitine deficiency is caused by mutations...
ACCEPT
Summary: Loss-of-function OCTN2 mutations abrogate carnitine transport and cause systemic carnitine deficiency, confirming OCTN2's role in carnitine transport. Core process.
Reason: Mutation/disease evidence directly supports OCTN2 involvement in carnitine transport; core process.
Supporting Evidence:
PMID:9916797
this mutation abrogates carnitine transport.
GO:0016324 apical plasma membrane
IDA
PMID:17274673
OCTN2-mediated carnitine uptake in a newly discovered human ...
ACCEPT
Summary: OCTN2 localized to the apical membrane of the human proximal tubule cell line Caki-1, where it mediates carnitine reabsorption. Core polarized localization in kidney.
Reason: Directly documented apical plasma-membrane localization in proximal tubule cells; correct.
Supporting Evidence:
PMID:17274673
an apical membrane expression pattern of OCTN2 in Caki-1 cells was discovered.
GO:0016324 apical plasma membrane
IDA
PMID:18641280
Expression and localization of carnitine/organic cation tran...
ACCEPT
Summary: OCTN2 predominantly localized to the apical membranes of human corneal and conjunctival epithelial cells, with apical L-carnitine uptake. Apical localization consistent across epithelia.
Reason: Directly documented apical plasma-membrane localization in ocular epithelia; correct.
Supporting Evidence:
PMID:18641280
OCTN1 and OCTN2 were predominately localized in the apical membranes of the cells.
GO:0030165 PDZ domain binding
IPI
PMID:15523054
PDZK1 directly regulates the function of organic cation/carn...
KEEP AS NON CORE
Summary: The OCTN2 C-terminal PDZ-binding motif (last four residues) binds the PDZ protein PDZK1 (and NHERF2), and PDZK1 co-expression stimulates OCTN2 carnitine transport capacity ~6-fold. An informative, functionally relevant molecular function (accessory regulatory interaction).
Reason: A specific, biologically meaningful protein-domain interaction that regulates OCTN2 transport; retained as an informative non-core molecular function (the core MF remains carnitine transport).
Supporting Evidence:
PMID:15523054
a specific interaction of apical transporters OCTN1 and OCTN2, but not basolateral transporters OCT1 and OCT2, with PDZK1
GO:0031526 brush border membrane
IDA
PMID:15238359
L-Carnitine transport in human placental brush-border membra...
ACCEPT
Summary: OCTN2 detected by Western blot in placental brush-border (but not basal) membrane vesicles. Brush-border (apical) localization consistent with the transporter's polarized reabsorptive/absorptive role.
Reason: Directly documented brush-border membrane localization; correct and informative (specific apical sub-localization).
Supporting Evidence:
PMID:15238359
OCTN2, a high-affinity, Na(+)-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles.
GO:0031526 brush border membrane
ISS
PMID:15523054
PDZK1 directly regulates the function of organic cation/carn...
ACCEPT
Summary: Brush-border membrane localization supported by sequence-similarity transfer (rat Octn2, Q9Z0E8) alongside the demonstrated colocalization of OCTN2 and PDZK1 in kidney brush-border membranes. Consistent with the direct human evidence.
Reason: Brush-border localization is corroborated directly (placenta, OCTN2/PDZK1 colocalization in kidney BBM) and by ISS from the rat ortholog; correct.
Supporting Evidence:
PMID:15523054
both PDZK1 and OCTN2 are colocalized in brush-border membranes of the kidney.
GO:0005886 plasma membrane
TAS
PMID:9916797
Primary systemic carnitine deficiency is caused by mutations...
ACCEPT
Summary: Author-asserted plasma-membrane localization of the carnitine transporter (membrane-physiological studies indicated a plasma-membrane carnitine transport defect in SCD). Consistent with the established core localization.
Reason: Traceable author statement of plasma-membrane carnitine transporter localization, corroborated by extensive direct evidence.
Supporting Evidence:
PMID:9916797
a defect of the carnitine transport system in the plasma membrane in SCD patients

Core Functions

Sodium-coupled, high-affinity import of L-carnitine across the plasma membrane. OCTN2 symports one Na+ with one (R)-carnitine molecule, enabling cellular uptake and renal reabsorption of carnitine that supplies the mitochondrial carnitine shuttle for long-chain fatty-acid beta-oxidation.

Supporting Evidence:
  • PMID:9685390
    OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.
  • PMID:10966938
    hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+).

Stereospecific (R)-carnitine transmembrane transporter activity, demonstrated directly in heterologous systems and native epithelia and lost in disease-causing SLC22A5 mutants; this is the specific-substrate resolution of the core carnitine transport function.

Supporting Evidence:
  • PMID:9916797
    this mutation abrogates carnitine transport.
  • PMID:17509700
    A novel organic cation transporter OCTN2 is indispensable for carnitine transport across plasma membrane

Sodium-dependent transport of carnitine and other zwitterionic/cationic organic solutes; the Na+-coupled symport mechanism underlies OCTN2's high-affinity carnitine uptake, while OCTN2 also transports organic cations more weakly in a Na+-independent manner (polyspecific secondary activity).

Supporting Evidence:

References

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Notes

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