LAT1_RABIT
ID LAT1_RABIT Reviewed; 503 AA.
AC Q7YQK4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 25-MAY-2022, entry version 81.
DE RecName: Full=Large neutral amino acids transporter small subunit 1;
DE AltName: Full=4F2 light chain;
DE Short=4F2 LC;
DE Short=4F2LC;
DE AltName: Full=L-type amino acid transporter 1;
DE AltName: Full=LAT1 {ECO:0000303|PubMed:12614332};
DE AltName: Full=Solute carrier family 7 member 5;
GN Name=SLC7A5 {ECO:0000250|UniProtKB:Q01650};
GN Synonyms=LAT1 {ECO:0000303|PubMed:12614332};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP47189.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF GLY-219 AND TRP-234.
RC STRAIN=New Zealand {ECO:0000269|PubMed:12614332};
RC TISSUE=Brain capillary {ECO:0000269|PubMed:12614332};
RX PubMed=12614332; DOI=10.1046/j.1471-4159.2003.01622.x;
RA Boado R.J., Li J.Y., Pardridge W.M.;
RT "Site-directed mutagenesis of rabbit LAT1 at amino acids 219 and 234.";
RL J. Neurochem. 84:1322-1331(2003).
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY, AND MISCELLANEOUS.
RX PubMed=12824232; DOI=10.1167/iovs.02-0907;
RA Jain-Vakkalagadda B., Dey S., Pal D., Mitra A.K.;
RT "Identification and functional characterization of a Na+-independent large
RT neutral amino acid transporter, LAT1, in human and rabbit cornea.";
RL Invest. Ophthalmol. Vis. Sci. 44:2919-2927(2003).
RN [3] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=14764922; DOI=10.1203/01.pdr.0000113461.07950.72;
RA Boado R.J., Li J.Y., Pardridge W.M.;
RT "Developmental regulation of the rabbit blood-brain barrier LAT1 large
RT neutral amino acid transporter mRNA and protein.";
RL Pediatr. Res. 55:557-560(2004).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF CYS-88; CYS-98; CYS-160; CYS-172; CYS-174; CYS-183; CYS-331;
RP CYS-377; CYS-403; CYS-439; CYS-454 AND CYS-492.
RX PubMed=16125134; DOI=10.1016/j.bbamem.2005.07.007;
RA Boado R.J., Li J.Y., Chu C., Ogoshi F., Wise P., Pardridge W.M.;
RT "Site-directed mutagenesis of cysteine residues of large neutral amino acid
RT transporter LAT1.";
RL Biochim. Biophys. Acta 1715:104-110(2005).
CC -!- FUNCTION: The heterodimer with SLC3A2 functions as sodium-independent,
CC high-affinity transporter that mediates uptake of large neutral amino
CC acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine,
CC methionine and tryptophan (PubMed:12614332, PubMed:16125134). Functions
CC as an amino acid exchanger (By similarity). May play a role in the
CC transport of L-DOPA across the blood-brain barrier (By similarity). May
CC act as the major transporter of tyrosine in fibroblasts (By
CC similarity). May mediate blood-to-retina L-leucine transport across the
CC inner blood-retinal barrier (By similarity). Can mediate the transport
CC of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the
CC cell membrane. When associated with LAPTM4B, the heterodimer formed by
CC SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake
CC into these organelles, and thereby mediates mTORC1 activation. Involved
CC in the uptake of toxic methylmercury (MeHg) when administered as the L-
CC cysteine or D,L-homocysteine complexes. Involved in the cellular
CC activity of small molecular weight nitrosothiols, via the
CC stereoselective transport of L-nitrosocysteine (L-CNSO) across the
CC membrane (By similarity). {ECO:0000250|UniProtKB:Q01650,
CC ECO:0000250|UniProtKB:Q63016, ECO:0000250|UniProtKB:Q9Z127,
CC ECO:0000269|PubMed:12614332, ECO:0000269|PubMed:16125134}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=27.0 uM for phenylalanine (in frog oocytes)
CC {ECO:0000269|PubMed:12614332};
CC KM=19.8 uM for phenylalanine (in frog oocytes)
CC {ECO:0000269|PubMed:16125134};
CC KM=47.8 uM for tryptophan (in frog oocytes)
CC {ECO:0000269|PubMed:12614332, ECO:0000269|PubMed:16125134};
CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport
CC protein SLC3A2/4F2hc (Probable) (PubMed:16125134). Interacts with
CC LAPTM4B; this recruits the heterodimer formed by SLC3A2 and SLC7A5 to
CC lysosomes to promote leucine uptake into these organelles and is
CC required for mTORC1 activation (By similarity).
CC {ECO:0000250|UniProtKB:Q01650, ECO:0000269|PubMed:16125134,
CC ECO:0000305|PubMed:12614332}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q01650}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q01650}. Cell membrane
CC {ECO:0000269|PubMed:12614332, ECO:0000269|PubMed:16125134}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q01650}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q01650}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q01650}. Note=Located to the plasma membrane by
CC SLC3A2/4F2hc. Localized to the apical membrane of placental
CC syncytiotrophoblastic cells. Recruited to lysosomes by LAPTM4B (By
CC similarity). Expressed in both luminal and abluminal membranes of brain
CC capillary endothelial cells (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q01650}.
CC -!- TISSUE SPECIFICITY: Expression detected in cornea.
CC {ECO:0000269|PubMed:12824232}.
CC -!- DEVELOPMENTAL STAGE: Levels remain unchanged during postnatal
CC development (at protein level). {ECO:0000269|PubMed:14764922}.
CC -!- MISCELLANEOUS: Phenylalanine transport is inhibited by mercury, L-
CC alanine and charged amino acids. {ECO:0000269|PubMed:12824232,
CC ECO:0000269|PubMed:16125134}.
CC -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC)
CC superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
CC {ECO:0000255}.
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DR EMBL; AF515772; AAP47189.1; -; mRNA.
DR RefSeq; NP_001075589.1; NM_001082120.1.
DR AlphaFoldDB; Q7YQK4; -.
DR SMR; Q7YQK4; -.
DR STRING; 9986.ENSOCUP00000025624; -.
DR GeneID; 100008844; -.
DR KEGG; ocu:100008844; -.
DR CTD; 8140; -.
DR eggNOG; KOG1287; Eukaryota.
DR InParanoid; Q7YQK4; -.
DR OrthoDB; 621852at2759; -.
DR SABIO-RK; Q7YQK4; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:1990184; C:amino acid transport complex; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015190; F:L-leucine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015196; F:L-tryptophan transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0042605; F:peptide antigen binding; IPI:UniProtKB.
DR GO; GO:1904556; P:L-tryptophan transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015804; P:neutral amino acid transport; IDA:UniProtKB.
DR InterPro; IPR002293; AA/rel_permease1.
DR InterPro; IPR004760; L_AA_transporter.
DR Pfam; PF13520; AA_permease_2; 1.
DR TIGRFAMs; TIGR00911; 2A0308; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Cell membrane; Disulfide bond; Lysosome; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..503
FT /note="Large neutral amino acids transporter small subunit
FT 1"
FT /id="PRO_0000252233"
FT TOPO_DOM 1..45
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 67..79
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 101..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 144..165
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 187..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 189..210
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 211..238
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 260..272
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 294..320
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 342..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 366..386
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 387..391
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 413..426
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 448..453
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 475..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 160
FT /note="Interchain (with C-210 in SLC3A2)"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT MUTAGEN 88
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Decreased KM and Vmax for Phe. Similar affect on
FT KM and Vmax for Phe; when associated with S-183."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 98
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Slightly decreased KM and Vmax for Phe. Slightly
FT less decreased KM and Vmax for Phe; when associated with S-
FT 183."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 160
FT /note="C->S: No change to KM or Vmax for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 172
FT /note="C->S: No change to KM or Vmax for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 174
FT /note="C->S: No change to KM or Vmax for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 183
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Slightly decreased KM and Vmax for Phe. Similar
FT affect on KM and Vmax for Phe; when associated with S-88.
FT Slightly less decreased KM and Vmax for Phe; when
FT associated with S-98."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 219
FT /note="G->D: Decreased KM and Vmax for Trp. Increased KM
FT and Vmax for Phe; when associated with L-234."
FT /evidence="ECO:0000269|PubMed:12614332"
FT MUTAGEN 234
FT /note="W->L: Decreased KM and Vmax for Trp. Increased KM
FT but decreased Vmax for Phe. Increased KM and Vmax for Phe;
FT when associated with D-219."
FT /evidence="ECO:0000269|PubMed:12614332"
FT MUTAGEN 331
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Increased KM and Vmax for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 377
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2)."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 403
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2)."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 439
FT /note="C->S: Prevents insertion into the plasma membrane
FT and possibly protein folding."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 454
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Slightly increased KM but slightly decreased Vmax
FT for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 492
FT /note="C->S: No significant effect on inhibition by
FT HgCl(2). Slightly decreased KM and Vmax for Phe."
FT /evidence="ECO:0000269|PubMed:16125134"
SQ SEQUENCE 503 AA; 54783 MW; DB3D649A74E8F9B3 CRC64;
MAGAGPKRRA AAAAAPEEER QAREKMLAAR REAEAEGEGV ALQRNITLLN GVAIIVGTII
GSGIFVTPTG VLKEAGSPGL SLVVWAVCGV FSIVGALCYA ELGTTITKSG GDYAYMLEVY
GSLPAFLKLW IELLIIRPSS QYIVALVFAT YLLKPVFPTC PVPEEAAKLV ACLCVLLLTA
VNCYSVKAAT RVQDAFAAAK LLALALIILL GFVQIGKGGV SNLDPKFSFE GTNWDVGNIV
LALYSGLFAY GGWNYLNFVT EEMINPYRNL PLAIIISLPI CTLVYVLTNL AYFTTLSPEQ
MLASEAVAVD FGNHHLGVMS WVIPVFVGLS CFGSVNGSLF TSSRLFFVGS REGHLPSVLS
MIHPQLLTPV PSLVFTCAMT LLYAFSRDIF SVINFFSFFN WLCVALAIIG MMWLRYKKPE
LERPIKVNLA LPVFFILACL FLIAVSFWKT PVECGIGFTI ILSGLPVYFF GVWWKNKPKW
LLQGIFSATA LCQKLMQVVP QET
