LAT2_RAT
ID LAT2_RAT Reviewed; 533 AA.
AC Q9WVR6;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Large neutral amino acids transporter small subunit 2;
DE AltName: Full=L-type amino acid transporter 2;
DE AltName: Full=Solute carrier family 7 member 8;
GN Name=Slc7a8; Synonyms=Lat2, Lat4;
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, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, TISSUE SPECIFICITY, AND INHIBITION.
RC TISSUE=Small intestine;
RX PubMed=10391916; DOI=10.1074/jbc.274.28.19745;
RA Segawa H., Fukasawa Y., Miyamoto K., Takeda E., Endou H., Kanai Y.;
RT "Identification and functional characterization of a Na+-independent
RT neutral amino acid transporter with broad substrate selectivity.";
RL J. Biol. Chem. 274:19745-19751(1999).
RN [2]
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 [3]
RP TISSUE SPECIFICITY.
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).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-29; SER-30 AND
RP SER-529, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Sodium-independent, high-affinity transport of small and
CC large neutral amino acids such as alanine, serine, threonine, cysteine,
CC phenylalanine, tyrosine, leucine, arginine and tryptophan, when
CC associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has
CC higher affinity for L-phenylalanine than LAT1 but lower affinity for
CC glutamine and serine. L-alanine is transported at physiological
CC concentrations. Plays a role in basolateral (re)absorption of neutral
CC amino acids. Involved in the uptake of methylmercury (MeHg) when
CC administered as the L-cysteine or D,L-homocysteine complexes, and hence
CC plays a role in metal ion homeostasis and toxicity. Involved in the
CC cellular activity of small molecular weight nitrosothiols, via the
CC stereoselective transport of L-nitrosocysteine (L-CNSO) across the
CC transmembrane. Plays an essential role in the reabsorption of neutral
CC amino acids from the epithelial cells to the bloodstream in the kidney.
CC {ECO:0000269|PubMed:10391916}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=119 uM for L-leucine {ECO:0000269|PubMed:10391916};
CC KM=265 uM for glycine {ECO:0000269|PubMed:10391916};
CC KM=187 uM for L-alanine {ECO:0000269|PubMed:10391916};
CC KM=116 uM for L-serine {ECO:0000269|PubMed:10391916};
CC KM=68.6 uM for L-threonine {ECO:0000269|PubMed:10391916};
CC KM=109 uM for L-cysteine {ECO:0000269|PubMed:10391916};
CC KM=80.7 uM for L-asparagine {ECO:0000269|PubMed:10391916};
CC KM=151 uM for L-glutamine {ECO:0000269|PubMed:10391916};
CC KM=96.7 uM for L-isoleucine {ECO:0000269|PubMed:10391916};
CC KM=124 uM for L-valine {ECO:0000269|PubMed:10391916};
CC KM=204 uM for L-methionine {ECO:0000269|PubMed:10391916};
CC KM=45 uM for L-phenylalanine {ECO:0000269|PubMed:10391916};
CC KM=35.9 uM for L-tyrosine {ECO:0000269|PubMed:10391916};
CC KM=57.6 uM for L-tryptophan {ECO:0000269|PubMed:10391916};
CC KM=181 uM for L-histidine {ECO:0000269|PubMed:10391916};
CC pH dependence:
CC Optimum pH is 6.25. {ECO:0000269|PubMed:10391916};
CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport
CC protein SLC3A2/4F2hc. {ECO:0000269|PubMed:10391916}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Basolateral cell
CC membrane {ECO:0000269|PubMed:16027961}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16027961}. Note=Localized to the cytoplasm when
CC expressed alone (By similarity). When coexpressed with SLC3A2/4F2hc, is
CC localized to the plasma membrane. Colocalized with SLC3A2/4F2hc at the
CC basolateral membrane of kidney cortex proximal tubules and small
CC intestine epithelia of the villi (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expression is seen in jejunum mucosa and the
CC epithelial cells of the jejunum, ileum and colon, as well as in kidney,
CC placenta, brain, testis and skeletal muscle. Expressed in retina, inner
CC blood-retinal barrier of retina, retinal vascular endothelial cells.
CC Also expressed in the intestinal epithelial cell line IEC-6 and in the
CC retinal capillary endothelial cell line TR-iBRB2.
CC {ECO:0000269|PubMed:10391916, ECO:0000269|PubMed:15980244,
CC ECO:0000269|PubMed:16027961}.
CC -!- MISCELLANEOUS: Leucine transport activity is inhibited by 2-amino-
CC bicyclo-(2,2,1)-heptane-2-carboxylate (BCH), glycine, L-isomers of the
CC neutral amino acids and histidine.
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; AB024400; BAA82517.1; -; mRNA.
DR RefSeq; NP_445894.1; NM_053442.1.
DR AlphaFoldDB; Q9WVR6; -.
DR SMR; Q9WVR6; -.
DR STRING; 10116.ENSRNOP00000019618; -.
DR TCDB; 2.A.3.8.6; the amino acid-polyamine-organocation (apc) family.
DR iPTMnet; Q9WVR6; -.
DR PhosphoSitePlus; Q9WVR6; -.
DR PaxDb; Q9WVR6; -.
DR Ensembl; ENSRNOT00000019618; ENSRNOP00000019618; ENSRNOG00000014311.
DR GeneID; 84551; -.
DR KEGG; rno:84551; -.
DR UCSC; RGD:619904; rat.
DR CTD; 23428; -.
DR RGD; 619904; Slc7a8.
DR eggNOG; KOG1287; Eukaryota.
DR GeneTree; ENSGT00940000158278; -.
DR InParanoid; Q9WVR6; -.
DR OMA; FTHLWND; -.
DR OrthoDB; 621852at2759; -.
DR PhylomeDB; Q9WVR6; -.
DR TreeFam; TF313355; -.
DR Reactome; R-RNO-210991; Basigin interactions.
DR Reactome; R-RNO-352230; Amino acid transport across the plasma membrane.
DR SABIO-RK; Q9WVR6; -.
DR PRO; PR:Q9WVR6; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000014311; Expressed in ovary and 19 other tissues.
DR Genevisible; Q9WVR6; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0009925; C:basal plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031528; C:microvillus membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015180; F:L-alanine 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; ISO:RGD.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015101; F:organic cation 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:0019534; F:toxin transmembrane transporter activity; ISO:RGD.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:RGD.
DR GO; GO:0006865; P:amino acid transport; ISO:RGD.
DR GO; GO:0015816; P:glycine transport; ISO:RGD.
DR GO; GO:1904273; P:L-alanine import across plasma membrane; ISO:RGD.
DR GO; GO:0015807; P:L-amino acid transport; ISO:RGD.
DR GO; GO:1903801; P:L-leucine import across plasma membrane; ISO:RGD.
DR GO; GO:0098713; P:leucine import across plasma membrane; ISO:RGD.
DR GO; GO:0015820; P:leucine transport; ISO:RGD.
DR GO; GO:0015804; P:neutral amino acid transport; ISS:UniProtKB.
DR GO; GO:0035524; P:proline transmembrane transport; ISO:RGD.
DR GO; GO:0070327; P:thyroid hormone transport; ISO:RGD.
DR GO; GO:0015827; P:tryptophan transport; ISO:RGD.
DR GO; GO:0015829; P:valine 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; Cytoplasm; Disulfide bond; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..533
FT /note="Large neutral amino acids transporter small subunit
FT 2"
FT /id="PRO_0000054275"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXW9"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 533 AA; 58190 MW; 99479DB60DA69DF0 CRC64;
MEKGTRQRNN TAKNHPDRGS DTSPEAEASS GGGGVALKKE IGLVSACGII VGNIIGSGIF
VSPKGVLENA GSVGLALIVW IVTGVITAVG ALCYAELGVT IPKSGGDYSY VKDIFGGLAG
FLRLWIAVLV IYPTNQAVIA LTFSNYVLQP LFPTCFPPES GLRLLAAICL LLLTWVNCSS
VRWATRVQDI FTAGKLLALA LIIIMGVVQI CKGEFFWLEP KNAFENFQEP DIGLVALAFL
QGSFAYGGWN FLNYVTEELV DPYKNLPRAI FISIPLVTFV YVFANIAYVT AMSPQELLAS
NAVAVTFGEK LLGVMAWIMP ISVALSTFGG VNGSLFTSSR LFFAGAREGH LPSVLAMIHV
KRCTPIPALL FTCLSTLLML VTSDMYTLIN YVGFINYLFY GVTVAGQIVL RWKKPDIPRP
IKISLLFPII YLLFWAFLLI FSLWSEPVVC GIGLAIMLTG VPVYFLGVYW QHKPKCFNDF
IESLTLVSQK MCVVVYPQEG DSGTEETIDD VEEQHKPIFQ PTPVKDPDSE EQP
