Q9UHI5 · LAT2_HUMAN
- ProteinLarge neutral amino acids transporter small subunit 2
- GeneSLC7A8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids535 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter (PubMed:11847106).
This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake (PubMed:10391915, PubMed:11847106).
May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney (PubMed:12716892).
Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity (PubMed:12117417).
Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (PubMed:15769744).
Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4) (By similarity).
Mediates the uptake of L-DOPA (By similarity).
May participate in auditory function (By similarity).
Catalytic activity
- L-histidine(in) + L-phenylalanine(out) = L-histidine(out) + L-phenylalanine(in)L-histidine (in)CHEBI:57595
+ L-phenylalanine (out)CHEBI:58095= L-histidine (out)CHEBI:57595+ L-phenylalanine (in)CHEBI:58095 - L-phenylalanine(out) + L-tryptophan(in) = L-phenylalanine(in) + L-tryptophan(out)
- L-isoleucine(in) + L-phenylalanine(out) = L-isoleucine(out) + L-phenylalanine(in)
- L-phenylalanine(out) + L-valine(in) = L-phenylalanine(in) + L-valine(out)
- L-leucine(in) + L-phenylalanine(out) = L-leucine(out) + L-phenylalanine(in)
- L-glutamine(in) + L-phenylalanine(out) = L-glutamine(out) + L-phenylalanine(in)
- L-cysteine(in) + L-phenylalanine(out) = L-cysteine(out) + L-phenylalanine(in)
- L-methionine(in) + L-phenylalanine(out) = L-methionine(out) + L-phenylalanine(in)
- L-leucine(out) + L-methionine(in) = L-leucine(in) + L-methionine(out)
- L-cysteine(out) + L-methionine(in) = L-cysteine(in) + L-methionine(out)
- L-methionine(in) + S-methylmercury-L-cysteine(out) = L-methionine(out) + S-methylmercury-L-cysteine(in)
- L-leucine(out) + S-methylmercury-L-cysteine(in) = L-leucine(in) + S-methylmercury-L-cysteine(out)
- L-phenylalanine(out) + S-methylmercury-L-cysteine(in) = L-phenylalanine(in) + S-methylmercury-L-cysteine(out)
- L-phenylalanine(out) + L-serine(in) = L-phenylalanine(in) + L-serine(out)
- glycine(in) + L-phenylalanine(out) = glycine(out) + L-phenylalanine(in)
- L-alanine(in) + L-phenylalanine(out) = L-alanine(out) + L-phenylalanine(in)
- 3,3'-diiodo-L-thyronine(out) = 3,3'-diiodo-L-thyronine(in)This reaction proceeds in the forward direction.
- 3,3',5-triiodo-L-thyronine(out) = 3,3',5-triiodo-L-thyronine(in)This reaction proceeds in the forward direction.
- L-dopa(out) + L-phenylalanine(in) = L-dopa(in) + L-phenylalanine(out)
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
36.5 μM | L-isoleucine (extracellular side) | |||||
7 mM | L-isoleucine | intracellular side | ||||
167 μM | L-alanine (extracellular side) | |||||
275 mM | L-alanine | intracellular side | ||||
4.2 mM | glycine (extracellular side) | |||||
2.6 mM | glycine | intracellular side | ||||
110.3 μM | L-glutamine | |||||
221 μM | L-leucine | |||||
64 μM | MeHg-L-cysteine | |||||
161 μM | methionine | |||||
978 μM | L-alanine | |||||
134 μM | L-alanine | |||||
89.35 μM | L-phenylalanine | |||||
52.7 μM | L-tryptophan | |||||
57.3 μM | L-tryptophan | |||||
48.8 μM | L-tyrosine |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
6706 pmol/min/mg | with L-glutamine as substrate | ||||
7376 pmol/min/mg | with L-alanine as substrate | ||||
4122 pmol/min/mg | with L-tryptophan as substrate | ||||
58.9 pmol/min/mg | with L-phenylalanine as substrate |
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 53 | L-leucine (UniProtKB | ChEBI); substrate | ||||
Sequence: I | ||||||
Binding site | 134 | L-tryptophan (UniProtKB | ChEBI); substrate | ||||
Sequence: N | ||||||
Site | 134 | Important for substrate specificity | ||||
Sequence: N | ||||||
Binding site | 246 | L-leucine (UniProtKB | ChEBI); substrate | ||||
Sequence: G | ||||||
Site | 246 | Important for substrate specificity | ||||
Sequence: G | ||||||
Binding site | 395 | L-tryptophan (UniProtKB | ChEBI); substrate | ||||
Sequence: N |
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLarge neutral amino acids transporter small subunit 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UHI5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-44 | Cytoplasmic | ||||
Sequence: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVS | ||||||
Transmembrane | 45-65 | Helical; Name=1 | ||||
Sequence: ACGIIVGNIIGSGIFVSPKGV | ||||||
Topological domain | 66-73 | Extracellular | ||||
Sequence: LENAGSVG | ||||||
Transmembrane | 74-95 | Helical; Name=2 | ||||
Sequence: LALIVWIVTGFITVVGALCYAE | ||||||
Topological domain | 96-116 | Cytoplasmic | ||||
Sequence: LGVTIPKSGGDYSYVKDIFGG | ||||||
Transmembrane | 117-149 | Helical; Name=3 | ||||
Sequence: LAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQP | ||||||
Topological domain | 150-157 | Extracellular | ||||
Sequence: LFPTCFPP | ||||||
Transmembrane | 158-178 | Helical; Name=4 | ||||
Sequence: ESGLRLLAAICLLLLTWVNCS | ||||||
Topological domain | 179-181 | Cytoplasmic | ||||
Sequence: SVR | ||||||
Transmembrane | 182-210 | Helical; Name=5 | ||||
Sequence: WATRVQDIFTAGKLLALALIIIMGIVQIC | ||||||
Topological domain | 211-230 | Extracellular | ||||
Sequence: KGEYFWLEPKNAFENFQEPD | ||||||
Transmembrane | 231-252 | Helical; Name=6 | ||||
Sequence: IGLVALAFLQGSFAYGGWNFLN | ||||||
Topological domain | 253-265 | Cytoplasmic | ||||
Sequence: YVTEELVDPYKNL | ||||||
Transmembrane | 266-287 | Helical; Name=7 | ||||
Sequence: PRAIFISIPLVTFVYVFANVAY | ||||||
Topological domain | 288-312 | Extracellular | ||||
Sequence: VTAMSPQELLASNAVAVTFGEKLLG | ||||||
Transmembrane | 313-338 | Helical; Name=8 | ||||
Sequence: VMAWIMPISVALSTFGGVNGSLFTSS | ||||||
Topological domain | 339-364 | Cytoplasmic | ||||
Sequence: RLFFAGAREGHLPSVLAMIHVKRCTP | ||||||
Transmembrane | 365-382 | Helical; Name=9 | ||||
Sequence: IPALLFTCISTLLMLVTS | ||||||
Topological domain | 383-386 | Extracellular | ||||
Sequence: DMYT | ||||||
Transmembrane | 387-408 | Helical; Name=10 | ||||
Sequence: LINYVGFINYLFYGVTVAGQIV | ||||||
Topological domain | 409-423 | Cytoplasmic | ||||
Sequence: LRWKKPDIPRPIKIN | ||||||
Transmembrane | 424-446 | Helical; Name=11 | ||||
Sequence: LLFPIIYLLFWAFLLVFSLWSEP | ||||||
Transmembrane | 447-466 | Helical; Name=12 | ||||
Sequence: VVCGIGLAIMLTGVPVYFLG | ||||||
Topological domain | 467-535 | Cytoplasmic | ||||
Sequence: VYWQHKPKCFSDFIELLTLVSQKMCVVVYPEVERGSGTEEANEDMEEQQQPMYQPTPTKDKDVAGQPQP |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 93 | Nearly complete reduction of glycine, L-alanine, and L-glutamine uptake. Minimal effect on the transport of L-isoleucine, L-histidine and L-tryptophan. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 134 | Reduces L-leucine uptake activity. Abolishes L-tryptophan uptake. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 134 | The substrate specificity changed dramatically reducing L-glutamine, glycine and L-alanine uptake activity thus mimicking the selectivity of SLC7A5. | ||||
Sequence: N → S | ||||||
Mutagenesis | 174 | Does not affect protein expression, plasma membrane localization, or L-alanine uptake. | ||||
Sequence: W → A | ||||||
Mutagenesis | 243 | Abolishes leucine and tryptophan transport activities. | ||||
Sequence: F → A | ||||||
Mutagenesis | 246 | Strong decrease in the uptake of large substrates L-tryptophan, L-glutamine, and L-histidine but increases the uptake of small neutral amino acids glycine and L-alanine. | ||||
Sequence: G → S | ||||||
Natural variant | VAR_088247 | 302 | found in a patient with age-related hearing loss; does not affect L-alanine transport activity. Decreases L-tyrosine transport activity; dbSNP:rs142951280 | |||
Sequence: V → I | ||||||
Mutagenesis | 395 | Strongly reduces L-leucine uptake activity. Strongly reduces L-tryptophan uptake activity. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 396 | Strongly reduces L-leucine uptake activity. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_088248 | 402 | found in a patient with age-related hearing loss; strongly decreased L-alanine transport activity. Decreases L-tyrosine transport activity; dbSNP:rs758342760 | |||
Sequence: T → M | ||||||
Natural variant | VAR_088249 | 418 | found in a patient with age-related hearing loss; decreases L-alanine transport activity. Decreases L-tyrosine transport activity; dbSNP:rs146946494 | |||
Sequence: R → C | ||||||
Natural variant | VAR_088250 | 460 | found in a patient with age-related hearing loss; strongly decreases L-alanine transport activity. Decreases L-tyrosine transport activity. Decreases cell membrane localization; dbSNP:rs2048595742 | |||
Sequence: V → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 597 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, disulfide bond.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000054273 | 1-535 | UniProt | Large neutral amino acids transporter small subunit 2 | |||
Sequence: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLLLLTWVNCSSVRWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEPDIGLVALAFLQGSFAYGGWNFLNYVTEELVDPYKNLPRAIFISIPLVTFVYVFANVAYVTAMSPQELLASNAVAVTFGEKLLGVMAWIMPISVALSTFGGVNGSLFTSSRLFFAGAREGHLPSVLAMIHVKRCTPIPALLFTCISTLLMLVTSDMYTLINYVGFINYLFYGVTVAGQIVLRWKKPDIPRPIKINLLFPIIYLLFWAFLLVFSLWSEPVVCGIGLAIMLTGVPVYFLGVYWQHKPKCFSDFIELLTLVSQKMCVVVYPEVERGSGTEEANEDMEEQQQPMYQPTPTKDKDVAGQPQP | |||||||
Modified residue (large scale data) | 21 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 24 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 29 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 29 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Disulfide bond | 154 | UniProt | Interchain (with C-210 in SLC3A2) | ||||
Sequence: C | |||||||
Modified residue (large scale data) | 522 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
ICAM-1 associates with the heterodimer SLC3A2/SLC7A8; this interaction regulates SLC7A8 activity (PubMed:12716892).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-20 | Basic and acidic residues | ||||
Sequence: MEEGARHRNNTEKKHPGGGE | ||||||
Region | 1-30 | Disordered | ||||
Sequence: MEEGARHRNNTEKKHPGGGESDASPEAGSG | ||||||
Region | 502-535 | Disordered | ||||
Sequence: SGTEEANEDMEEQQQPMYQPTPTKDKDVAGQPQP | ||||||
Compositional bias | 513-535 | Polar residues | ||||
Sequence: EQQQPMYQPTPTKDKDVAGQPQP |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q9UHI5-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length535
- Mass (Da)58,382
- Last updated2000-05-01 v1
- ChecksumAC129146353F1E47
Q9UHI5-2
- Name2
- Differences from canonical
- 1-203: Missing
Q9UHI5-3
- Name3
- Differences from canonical
- 1-263: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLLLLTWVNCSSVRWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEPDIGLVALAFLQGSFAYGGWNFLNYVTEELVDPYK → MGQLFQCAVGHPGSRHLHSWEAPGLGPDYHHGDCTDMQR
Q9UHI5-4
- Name4
- Differences from canonical
- 1-169: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICL → MGQYGQELSWKCLVKAVCLQEHSQPSQLLCTLLLCWCVLGRERPFRKAQSTSSPLEGVPRFLKR
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-20 | Basic and acidic residues | ||||
Sequence: MEEGARHRNNTEKKHPGGGE | ||||||
Alternative sequence | VSP_046947 | 1-169 | in isoform 4 | |||
Sequence: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICL → MGQYGQELSWKCLVKAVCLQEHSQPSQLLCTLLLCWCVLGRERPFRKAQSTSSPLEGVPRFLKR | ||||||
Alternative sequence | VSP_046946 | 1-203 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_046945 | 1-263 | in isoform 3 | |||
Sequence: MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLLLLTWVNCSSVRWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEPDIGLVALAFLQGSFAYGGWNFLNYVTEELVDPYK → MGQLFQCAVGHPGSRHLHSWEAPGLGPDYHHGDCTDMQR | ||||||
Sequence conflict | 225 | in Ref. 3; CAB40137 | ||||
Sequence: N → D | ||||||
Sequence conflict | 401 | in Ref. 3; CAB40137 | ||||
Sequence: V → G | ||||||
Sequence conflict | 503 | in Ref. 1; AAF05696/AAF05697 | ||||
Sequence: G → R | ||||||
Compositional bias | 513-535 | Polar residues | ||||
Sequence: EQQQPMYQPTPTKDKDVAGQPQP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF135828 EMBL· GenBank· DDBJ | AAF05695.1 EMBL· GenBank· DDBJ | mRNA | ||
AF135829 EMBL· GenBank· DDBJ | AAF05696.1 EMBL· GenBank· DDBJ | mRNA | ||
AF135830 EMBL· GenBank· DDBJ | AAF05697.1 EMBL· GenBank· DDBJ | mRNA | ||
AF171669 EMBL· GenBank· DDBJ | AAF20381.1 EMBL· GenBank· DDBJ | mRNA | ||
Y18483 EMBL· GenBank· DDBJ | CAB40137.1 EMBL· GenBank· DDBJ | mRNA | ||
AB037669 EMBL· GenBank· DDBJ | BAB21519.1 EMBL· GenBank· DDBJ | mRNA | ||
BX248288 EMBL· GenBank· DDBJ | CAD62616.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK296702 EMBL· GenBank· DDBJ | BAG59296.1 EMBL· GenBank· DDBJ | mRNA | ||
AK300384 EMBL· GenBank· DDBJ | BAG62118.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313465 EMBL· GenBank· DDBJ | BAG36251.1 EMBL· GenBank· DDBJ | mRNA | ||
AL117258 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471078 EMBL· GenBank· DDBJ | EAW66181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471078 EMBL· GenBank· DDBJ | EAW66182.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC052250 EMBL· GenBank· DDBJ | AAH52250.1 EMBL· GenBank· DDBJ | mRNA |