LAT1_RAT
ID LAT1_RAT Reviewed; 512 AA.
AC Q63016; Q9QWL4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 157.
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=Integral membrane protein E16;
DE Short=Protein TA1 {ECO:0000303|PubMed:7532544};
DE AltName: Full=L-type amino acid transporter 1 {ECO:0000303|PubMed:15980244};
DE Short=LAT-1 {ECO:0000303|PubMed:15120633};
DE AltName: Full=Solute carrier family 7 member 5;
GN Name=Slc7a5;
GN Synonyms=Lat1 {ECO:0000303|PubMed:9726963}, Mpe16,
GN Ta1 {ECO:0000303|PubMed:7532544};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP TISSUE SPECIFICITY.
RX PubMed=9726963; DOI=10.1074/jbc.273.37.23629;
RA Kanai Y., Segawa H., Miyamoto K., Uchino H., Takeda E., Endou H.;
RT "Expression cloning and characterization of a transporter for large neutral
RT amino acids activated by the heavy chain of 4F2 antigen (CD98).";
RL J. Biol. Chem. 273:23629-23632(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 272-512, AND TISSUE SPECIFICITY.
RC TISSUE=Hepatoma;
RX PubMed=7532544;
RA Sang J., Lim Y.P., Panzica M., Finch P., Thompson N.L.;
RT "TA1, a highly conserved oncofetal complementary DNA from rat hepatoma,
RT encodes an integral membrane protein associated with liver development,
RT carcinogenesis, and cell activation.";
RL Cancer Res. 55:1152-1159(1995).
RN [3]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11095508; DOI=10.1097/00001756-200011090-00021;
RA Matsuo H., Tsukada S., Nakata T., Chairoungdua A., Kim D.K., Cha S.H.,
RA Inatomi J., Yorifuji H., Fukuda J., Endou H., Kanai Y.;
RT "Expression of a system L neutral amino acid transporter at the blood-brain
RT barrier.";
RL NeuroReport 11:3507-3511(2000).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15120633; DOI=10.1016/j.bbrc.2004.04.062;
RA Padbury J.F., Diah S.K., McGonnigal B., Miller C., Fugere C., Kuzniar M.,
RA Thompson N.L.;
RT "Transcriptional regulation of the LAT-1/CD98 light chain.";
RL Biochem. Biophys. Res. Commun. 318:529-534(2004).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16027961; DOI=10.1007/s00726-005-0221-x;
RA Fraga S., Pinho M.J., Soares-da-Silva P.;
RT "Expression of LAT1 and LAT2 amino acid transporters in human and rat
RT intestinal epithelial cells.";
RL Amino Acids 29:229-233(2005).
RN [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INHIBITION.
RX PubMed=15980244; DOI=10.1167/iovs.04-1175;
RA Tomi M., Mori M., Tachikawa M., Katayama K., Terasaki T., Hosoya K.;
RT "L-type amino acid transporter 1-mediated L-leucine transport at the inner
RT blood-retinal barrier.";
RL Invest. Ophthalmol. Vis. Sci. 46:2522-2530(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:9726963). Functions as an amino acid
CC exchanger (By similarity). May play a role in the transport of L-DOPA
CC across the blood-brain barrier (By similarity). May act as the major
CC transporter of tyrosine in fibroblasts (By similarity). May mediate
CC blood-to-retina L-leucine transport across the inner blood-retinal
CC barrier (Probable). Can mediate the transport of thyroid hormones
CC triiodothyronine (T3) and thyroxine (T4) across the cell membrane. When
CC associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is
CC recruited to lysosomes to promote leucine uptake into these organelles,
CC and thereby mediates mTORC1 activation. Involved in the uptake of toxic
CC methylmercury (MeHg) when administered as the L-cysteine or D,L-
CC homocysteine complexes. Involved in the cellular activity of small
CC molecular weight nitrosothiols, via the stereoselective transport of L-
CC nitrosocysteine (L-CNSO) across the membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q01650, ECO:0000250|UniProtKB:Q9Z127,
CC ECO:0000269|PubMed:9726963, ECO:0000305|PubMed:15980244}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.1 uM for L-leucine {ECO:0000269|PubMed:15980244};
CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport
CC protein SLC3A2/4F2hc (PubMed:9726963). Interacts with LAPTM4B; this
CC recruits the heterodimer formed by SLC3A2 and SLC7A5 to lysosomes to
CC promote leucine uptake into these organelles and is required for mTORC1
CC activation (By similarity). {ECO:0000250|UniProtKB:Q01650,
CC ECO:0000269|PubMed:9726963}.
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:16027961, ECO:0000269|PubMed:9726963}; 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: Expressed in hepatoma but not in normal liver. Also
CC expressed in placenta, testis, brain, ovary, spleen, mammary gland, and
CC uterus. In brain expressed on capillary endothelia in cerebral cortex.
CC Expressed in jejunum mucosa and the epithelial cells of the jejunum,
CC ileum and colon. Also expressed in the intestinal epithelial cell line
CC IEC-6. Expressed in the brain, retina, inner blood-retinal barrier of
CC retina, retinal vascular endothelial cells, and in the retinal
CC capillary endothelial cell line TR-iBRB2. {ECO:0000269|PubMed:11095508,
CC ECO:0000269|PubMed:15120633, ECO:0000269|PubMed:15980244,
CC ECO:0000269|PubMed:16027961, ECO:0000269|PubMed:7532544,
CC ECO:0000269|PubMed:9726963}.
CC -!- INDUCTION: Expression induced in normal hepatic cells cultured in
CC arginine-depleted medium. {ECO:0000269|PubMed:15120633}.
CC -!- MISCELLANEOUS: L-leucine uptake by TR-iBRB2 cells was inhibited by L-
CC leucine, L-phenylalanine, L-methionine, L-isoleucine, L-valine, L-
CC tyrosine, L-tryptophan, D-leucine, D-phenylalanine, D-methionine and by
CC 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) (a specific
CC inhibitor of system L transport).
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:0000305}.
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DR EMBL; AB015432; BAA33035.1; -; mRNA.
DR EMBL; U00995; AAA74411.1; -; mRNA.
DR RefSeq; NP_059049.1; NM_017353.1.
DR AlphaFoldDB; Q63016; -.
DR SMR; Q63016; -.
DR BioGRID; 248432; 1.
DR IntAct; Q63016; 1.
DR STRING; 10116.ENSRNOP00000025784; -.
DR BindingDB; Q63016; -.
DR ChEMBL; CHEMBL4149; -.
DR DrugCentral; Q63016; -.
DR TCDB; 2.A.3.8.1; the amino acid-polyamine-organocation (apc) family.
DR jPOST; Q63016; -.
DR PaxDb; Q63016; -.
DR PRIDE; Q63016; -.
DR Ensembl; ENSRNOT00000025784; ENSRNOP00000025784; ENSRNOG00000018824.
DR GeneID; 50719; -.
DR KEGG; rno:50719; -.
DR UCSC; RGD:620639; rat.
DR CTD; 8140; -.
DR RGD; 620639; Slc7a5.
DR eggNOG; KOG1287; Eukaryota.
DR GeneTree; ENSGT00940000155581; -.
DR HOGENOM; CLU_007946_3_0_1; -.
DR InParanoid; Q63016; -.
DR OMA; RDRHLPH; -.
DR OrthoDB; 621852at2759; -.
DR PhylomeDB; Q63016; -.
DR TreeFam; TF313355; -.
DR Reactome; R-RNO-210991; Basigin interactions.
DR Reactome; R-RNO-352230; Amino acid transport across the plasma membrane.
DR Reactome; R-RNO-71240; Tryptophan catabolism.
DR SABIO-RK; Q63016; -.
DR PRO; PR:Q63016; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000018824; Expressed in pancreas and 20 other tissues.
DR Genevisible; Q63016; RN.
DR GO; GO:1990184; C:amino acid transport complex; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0098591; C:external side of apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031528; C:microvillus membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0015297; F:antiporter activity; IEA:Ensembl.
DR GO; GO:0015173; F:aromatic amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; ISO:RGD.
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:0015175; F:neutral amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB.
DR GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; ISO:RGD.
DR GO; GO:0089718; P:amino acid import across plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEP:RGD.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEP:RGD.
DR GO; GO:1903577; P:cellular response to L-arginine; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0015818; P:isoleucine transport; IMP:RGD.
DR GO; GO:0015807; P:L-amino acid transport; IMP:RGD.
DR GO; GO:1903801; P:L-leucine import across plasma membrane; ISO:RGD.
DR GO; GO:1904556; P:L-tryptophan transmembrane transport; ISS:UniProtKB.
DR GO; GO:0098713; P:leucine import across plasma membrane; ISO:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; IDA:RGD.
DR GO; GO:0015804; P:neutral amino acid transport; ISS:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IEP:RGD.
DR GO; GO:0015823; P:phenylalanine transport; ISO:RGD.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:RGD.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISO:RGD.
DR GO; GO:1905534; P:positive regulation of leucine import across plasma membrane; IMP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0070327; P:thyroid hormone transport; ISO:RGD.
DR GO; GO:0015829; P:valine transport; IMP:RGD.
DR GO; GO:0042908; P:xenobiotic transport; ISO:RGD.
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 Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..512
FT /note="Large neutral amino acids transporter small subunit
FT 1"
FT /id="PRO_0000054272"
FT TOPO_DOM 1..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 72..84
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 106..127
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 149..170
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 171..191
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 192..193
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 194..215
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 216..247
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 269..281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 303..329
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 330..350
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 351..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 396..400
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 401..421
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 422..435
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 436..456
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 457..462
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 463..483
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT TOPO_DOM 484..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 46
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
FT DISULFID 165
FT /note="Interchain (with C-210 in SLC3A2)"
FT /evidence="ECO:0000250|UniProtKB:Q01650"
SQ SEQUENCE 512 AA; 55903 MW; B487CE0B58D73A02 CRC64;
MAVAGAKRRA VAAPATTAAE EERQAREKML EARRGDGADP EGEGVTLQRN ITLINGVAII
VGTIIGSGIF VTPTGVLKEA GSPGLSLVVW AVCGVFSIVG ALCYAELGTT ISKSGGDYAY
MLEVYGSLPA FLKLWIELLI IRPSSQYIVA LVFATYLLKP VFPTCPVPEE AAKLVACLCV
LLLTAVNCYS VKAATRVQDA FAAAKLLALA LIILLGFIQM GKDIGQGDAS NLHQKLSFEG
TNLDVGNIVL ALYSGLFAYG GWNYLNFVTE EMINPYRNLP LAIIISLPIV TLVYVLTNLA
YFTTLSTNQM LTSEAVAVDF GNYHLGVMSW IIPVFVGLSC FGSVNGSLFT SSRLFFVGSR
EGHLPSILSM IHPQLLTPVP SLVFTCVMTL MYAFSRDIFS IINFFSFFNW LCVALAIIGM
MWLRFKKPEL ERPIKVNLAL PVFFILACLF LIAVSFWKTP LECGIGFAII LSGLPVYFFG
VWWKNKPKWI LQVIFSVTVL CQKLMQVVPQ ET
