Q9Y289 · SC5A6_HUMAN
- ProteinSodium-dependent multivitamin transporter
- GeneSLC5A6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids635 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide (PubMed:10329687, PubMed:15561972, PubMed:19211916, PubMed:20980265, PubMed:21570947, PubMed:22015582, PubMed:25809983, PubMed:25971966, PubMed:27904971, PubMed:28052864, PubMed:31754459).
Functions as a Na+-coupled substrate symporter where the stoichiometry of Na+:substrate is 2:1, creating an electrochemical Na+ gradient used as driving force for substrate uptake (PubMed:10329687, PubMed:20980265).
Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:19211916).
Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity).
Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (PubMed:25809983).
Functions as a Na+-coupled substrate symporter where the stoichiometry of Na+:substrate is 2:1, creating an electrochemical Na+ gradient used as driving force for substrate uptake (PubMed:10329687, PubMed:20980265).
Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:19211916).
Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity).
Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (PubMed:25809983).
Catalytic activity
- biotin(out) + 2 Na+(out) = biotin(in) + 2 Na+(in)
- (R)-pantothenate(out) + 2 Na+(out) = (R)-pantothenate(in) + 2 Na+(in)
- (R)-lipoate(out) + 2 Na+(out) = (R)-lipoate(in) + 2 Na+(in)
- iodide(out) + 2 Na+(out) = iodide(in) + 2 Na+(in)
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
18.91 μM | biotin | 37 | in retinal pigment epithelial cells | |||
14.28 μM | biotin | |||||
4 μM | lipoate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.0967 pmol/min/mg | 37 | for biotin uptake, in retinal pigment epithelial cells |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basal plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | brush border membrane | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Molecular Function | biotin transmembrane transporter activity | |
Molecular Function | iodide transmembrane transporter activity | |
Molecular Function | monocarboxylate:sodium symporter activity | |
Molecular Function | pantothenate transmembrane transporter activity | |
Molecular Function | pantothenate:sodium symporter activity | |
Molecular Function | sodium-dependent multivitamin transmembrane transporter activity | |
Molecular Function | vitamin transmembrane transporter activity | |
Biological Process | biotin import across plasma membrane | |
Biological Process | biotin metabolic process | |
Biological Process | biotin transport | |
Biological Process | iodide transmembrane transport | |
Biological Process | pantothenate transmembrane transport | |
Biological Process | sodium ion transport | |
Biological Process | transport across blood-brain barrier |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSodium-dependent multivitamin transporter
- Short namesNa(+)-dependent multivitamin transporter ; hSMVT
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y289
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Note: (Microbial infection) Exposure to E.coli lipopolysaccharides leads to reduced cell membrane localization.
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 24-44 | Helical | ||||
Sequence: FSIMDYVVFVLLLVLSLAIGL | ||||||
Transmembrane | 68-88 | Helical | ||||
Sequence: CLPVALSLLATFQSAVAILGV | ||||||
Transmembrane | 101-121 | Helical | ||||
Sequence: FLGCCYFLGLLIPAHIFIPVF | ||||||
Transmembrane | 143-163 | Helical | ||||
Sequence: VCGTVTFIFQMVIYMGVVLYA | ||||||
Transmembrane | 176-196 | Helical | ||||
Sequence: LWLSVLALGIVCTVYTALGGL | ||||||
Transmembrane | 199-219 | Helical | ||||
Sequence: VIWTDVFQTLVMFLGQLAVII | ||||||
Transmembrane | 256-276 | Helical | ||||
Sequence: FWTLAFGGVFMMLSLYGVNQA | ||||||
Transmembrane | 297-317 | Helical | ||||
Sequence: VFPFQQVSLCVGCLIGLVMFA | ||||||
Transmembrane | 336-356 | Helical | ||||
Sequence: FVLYFVMDLLKGLPGLPGLFI | ||||||
Transmembrane | 396-416 | Helical | ||||
Sequence: IMLSRGLAFGYGLLCLGMAYI | ||||||
Transmembrane | 428-448 | Helical | ||||
Sequence: ISIFGMVGGPLLGLFCLGMFF | ||||||
Transmembrane | 456-476 | Helical | ||||
Sequence: AVVGLLAGLVMAFWIGIGSIV | ||||||
Transmembrane | 528-548 | Helical | ||||
Sequence: LWYSAHNSTTVIVVGLIVSLL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Sodium-dependent multivitamin transporter deficiency (SMVTD)
- Note
- DescriptionAn autosomal recessive multisystemic metabolic disorder characterized by early infantile onset, progressive neurodegeneration, global developmental delay, and developmental regression with loss of early motor and cognitive milestones. Additional variable features include seizures, ataxia, spasticity, peripheral neuropathy, immune defects, and osteopenia. Treatment with biotin, pantothenic acid, and lipoate may result in clinical improvement.
- See alsoMIM:618973
Natural variants in SMVTD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_084535 | 94-635 | missing | in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778 | |
VAR_084536 | 123 | R>L | in SMVTD; reduced membrane localization; impaired biotin transport | |
VAR_084537 | 400 | R>T | in SMVTD; impaired biotin transport; dbSNP:rs370950187 |
Peripheral motor neuropathy, childhood-onset, biotin-responsive (COMNB)
- Note
- DescriptionAn autosomal recessive disorder characterized by distal muscle weakness and atrophy appearing late in the first decade of life. The disorder predominantly affects the upper limbs and hands, resulting in difficulties with fine motor skills. Some patients may have lower limb involvement, resulting in gait difficulties. Additional features may include spasticity, ataxia, and cerebellar signs. Sensation is intact, and patients have normal cognitive development. Treatment with biotin, pantothenic acid, and lipoic acid may result in clinical improvement.
- See alsoMIM:619903
Natural variants in COMNB
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_084535 | 94-635 | missing | in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778 | |
VAR_087446 | 162 | Y>C | in COMNB; no effect on membrane localization | |
VAR_087447 | 429 | S>G | in COMNB; no effect on membrane localization |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 68 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 78 | Reduced membrane localization. Decrease in biotin transport. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_084535 | 94-635 | in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778 | |||
Sequence: Missing | ||||||
Mutagenesis | 104 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_084536 | 123 | in SMVTD; reduced membrane localization; impaired biotin transport | |||
Sequence: R → L | ||||||
Mutagenesis | 128 | No effect on biotin transport. | ||||
Sequence: S → A | ||||||
Mutagenesis | 138 | Reduced protein levels. Decrease in biotin transport. | ||||
Sequence: N → A | ||||||
Mutagenesis | 144 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_087446 | 162 | in COMNB; no effect on membrane localization | |||
Sequence: Y → C | ||||||
Mutagenesis | 187 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 242 | No effect on biotin transport. | ||||
Sequence: S → A | ||||||
Mutagenesis | 283 | No effect on protein levels or membrane localization. | ||||
Sequence: S → A | ||||||
Mutagenesis | 286 | Resistant to phorbol 12-myristate 13-acetate (PMA)-induced inhibition of biotin transport. No effect on protein levels or membrane localization. | ||||
Sequence: T → A | ||||||
Mutagenesis | 294 | Reduced membrane localization. Decrease in biotin transport (decreased Vmax, no change in Km). | ||||
Sequence: C → A | ||||||
Mutagenesis | 294 | Decrease in biotin transport. | ||||
Sequence: C → S or M | ||||||
Mutagenesis | 309 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 358 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 366 | No effect on biotin transport. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_084537 | 400 | in SMVTD; impaired biotin transport; dbSNP:rs370950187 | |||
Sequence: R → T | ||||||
Mutagenesis | 410 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_087447 | 429 | in COMNB; no effect on membrane localization | |||
Sequence: S → G | ||||||
Mutagenesis | 443 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 450 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_052491 | 481 | in dbSNP:rs1395 | |||
Sequence: S → F | ||||||
Mutagenesis | 489 | Slight decrease in protein levels. Decrease in biotin transport. | ||||
Sequence: N → A | ||||||
Natural variant | VAR_052492 | 492 | in dbSNP:rs1064845 | |||
Sequence: S → N | ||||||
Mutagenesis | 498 | No effect on biotin transport. | ||||
Sequence: N → A | ||||||
Mutagenesis | 534 | No effect on biotin transport. | ||||
Sequence: N → A | ||||||
Mutagenesis | 567-635 | Loss of biotin transport. Loss of membrane localization. | ||||
Sequence: Missing | ||||||
Mutagenesis | 570-635 | Loss of biotin transport. Loss of membrane localization. | ||||
Sequence: Missing | ||||||
Mutagenesis | 575-635 | Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 577 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 583 | No effect on biotin transport. | ||||
Sequence: C → A | ||||||
Mutagenesis | 584-635 | Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 600-635 | Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 612-635 | Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 616-635 | Loss of apical membrane localization in polarized cells. Basolateral localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 620-635 | Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 624-635 | Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 627 | No effect on biotin transport. | ||||
Sequence: T → A | ||||||
Mutagenesis | 628 | Decrease in biotin transport. | ||||
Sequence: C → A or S | ||||||
Mutagenesis | 632-635 | Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 731 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000105386 | 1-635 | UniProt | Sodium-dependent multivitamin transporter | |||
Sequence: MSVGVSTSAPLSPTSGTSVGMSTFSIMDYVVFVLLLVLSLAIGLYHACRGWGRHTVGELLMADRKMGCLPVALSLLATFQSAVAILGVPSEIYRFGTQYWFLGCCYFLGLLIPAHIFIPVFYRLHLTSAYEYLELRFNKTVRVCGTVTFIFQMVIYMGVVLYAPSLALNAVTGFDLWLSVLALGIVCTVYTALGGLKAVIWTDVFQTLVMFLGQLAVIIVGSAKVGGLGRVWAVASQHGRISGFELDPDPFVRHTFWTLAFGGVFMMLSLYGVNQAQVQRYLSSRTEKAAVLSCYAVFPFQQVSLCVGCLIGLVMFAYYQEYPMSIQQAQAAPDQFVLYFVMDLLKGLPGLPGLFIACLFSGSLSTISSAFNSLATVTMEDLIRPWFPEFSEARAIMLSRGLAFGYGLLCLGMAYISSQMGPVLQAAISIFGMVGGPLLGLFCLGMFFPCANPPGAVVGLLAGLVMAFWIGIGSIVTSMGSSMPPSPSNGSSFSLPTNLTVATVTTLMPLTTFSKPTGLQRFYSLSYLWYSAHNSTTVIVVGLIVSLLTGRMRGRSLNPATIYPVLPKLLSLLPLSCQKRLHCRSYGQDHLDTGLFPEKPRNGVLGDSRDKEAMALDGTAYQGSSSTCILQETSL | |||||||
Glycosylation | 138 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 489 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 498 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue (large scale data) | 585 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
May be glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with PDZD11.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y289 | PDZD11 Q5EBL8 | 6 | EBI-3915941, EBI-1644207 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Domain
The C-terminal tail is important for biotin uptake as well as apical localization in polarized cells.
Sequence similarities
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length635
- Mass (Da)68,642
- Last updated2009-05-05 v2
- Checksum52A6E40DB337134F
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF116241 EMBL· GenBank· DDBJ | AAD37502.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF069307 EMBL· GenBank· DDBJ | AAD31727.1 EMBL· GenBank· DDBJ | mRNA | ||
AF081571 EMBL· GenBank· DDBJ | AAD37481.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314545 EMBL· GenBank· DDBJ | BAG37132.1 EMBL· GenBank· DDBJ | mRNA | ||
AC013403 EMBL· GenBank· DDBJ | AAX93172.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00620.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00621.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00622.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC012806 EMBL· GenBank· DDBJ | AAH12806.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015631 EMBL· GenBank· DDBJ | AAH15631.1 EMBL· GenBank· DDBJ | mRNA |