4F2_RAT
ID 4F2_RAT Reviewed; 527 AA.
AC Q794F9;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=4F2 cell-surface antigen heavy chain {ECO:0000250|UniProtKB:P08195};
DE Short=4F2hc {ECO:0000250|UniProtKB:P08195};
DE AltName: Full=Solute carrier family 3 member 2 {ECO:0000250|UniProtKB:P08195};
DE AltName: CD_antigen=CD98;
GN Name=Slc3a2 {ECO:0000312|RGD:3073};
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] {ECO:0000269|PubMed:9480885, ECO:0000312|EMBL:AAC53560.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAC53560.1};
RC TISSUE=Jejunal epithelium {ECO:0000312|EMBL:AAC53560.1};
RX PubMed=9480885; DOI=10.1042/bj3300745;
RA Yao S.Y.M., Muzyka W.R., Elliott J.F., Cheeseman C.I., Young J.D.;
RT "Cloning and functional expression of a cDNA from rat jejunal epithelium
RT encoding a protein (4F2hc) with system y+L amino acid transport activity.";
RL Biochem. J. 330:745-752(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAA33036.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Glial tumor {ECO:0000269|PubMed:9726963};
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
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 [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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 [6]
RP 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 [7]
RP FUNCTION, AND 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND THR-5, AND
RP 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: Component of several heterodimeric complexes involved in
CC amino acid transport (PubMed:9480885, PubMed:9726963, PubMed:10391916).
CC The precise substrate specificity depends on the other subunit in the
CC heterodimer (By similarity). The complexes function as amino acid
CC exchangers (PubMed:9480885). The homodimer functions as sodium-
CC independent, high-affinity transporter that mediates uptake of large
CC neutral amino acids such as phenylalanine, tyrosine, L-DOPA, leucine,
CC histidine, methionine and tryptophan (PubMed:9726963). The heterodimer
CC formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7 mediates the uptake of
CC dibasic amino acids (By similarity). The heterodimer with SLC7A5/LAT1
CC mediates the transport of thyroid hormones triiodothyronine (T3) and
CC thyroxine (T4) across the cell membrane (By similarity). The
CC heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic
CC methylmercury (MeHg) when administered as the L-cysteine or D,L-
CC homocysteine complexes (By similarity). The heterodimer with
CC SLC7A5/LAT1 is involved in the uptake of leucine (By similarity). When
CC associated with LAPTM4B, the heterodimer with SLC7A5/LAT1 is recruited
CC to lysosomes to promote leucine uptake into these organelles, and
CC thereby mediates mTORC1 activation (By similarity). The heterodimer
CC with SLC7A5/LAT1 may play a role in the transport of L-DOPA across the
CC blood-brain barrier (By similarity). The heterodimer formed by SLC3A2
CC and SLC7A5/LAT1 or SLC3A2 and SLC7A8/LAT2 is involved in the cellular
CC activity of small molecular weight nitrosothiols, via the
CC stereoselective transport of L-nitrosocysteine (L-CNSO) across the
CC transmembrane (By similarity). Together with ICAM1, regulates the
CC transport activity of SLC7A8/LAT2 in polarized intestinal cells by
CC generating and delivering intracellular signals (By similarity).
CC Required for targeting of SLC7A5/LAT1 and SLC7A8/LAT2 to the plasma
CC membrane and for channel activity (By similarity). Plays a role in
CC nitric oxide synthesis in human umbilical vein endothelial cells
CC (HUVECs) via transport of L-arginine (By similarity). May mediate
CC blood-to-retina L-leucine transport across the inner blood-retinal
CC barrier (Probable). {ECO:0000250|UniProtKB:P08195,
CC ECO:0000250|UniProtKB:P10852, ECO:0000269|PubMed:10391916,
CC ECO:0000269|PubMed:9480885, ECO:0000269|PubMed:9726963,
CC ECO:0000305|PubMed:15980244}.
CC -!- SUBUNIT: Disulfide-linked heterodimer with a non-glycosylated light
CC chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11) (Probable)
CC (PubMed:9726963, PubMed:10391916). Interacts with TLCD3A/CT120 and
CC ICAM1. Constitutively and specifically associates with beta-1 integrins
CC (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1),
CC but minimally with alpha-4/beta-1. Interacts with LAPTM4B; recruits
CC SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these
CC organelles and is required for mTORC1 activation (By similarity).
CC {ECO:0000250|UniProtKB:P08195, ECO:0000269|PubMed:10391916,
CC ECO:0000269|PubMed:9726963, ECO:0000305|PubMed:9480885}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P08195}. Cell membrane
CC {ECO:0000269|PubMed:10391916, ECO:0000269|PubMed:11095508,
CC ECO:0000269|PubMed:9480885, ECO:0000269|PubMed:9726963}; Single-pass
CC type II membrane protein {ECO:0000250|UniProtKB:P08195}. Cell junction
CC {ECO:0000250|UniProtKB:P10852}. Lysosome membrane
CC {ECO:0000250|UniProtKB:P08195}. Melanosome
CC {ECO:0000250|UniProtKB:P08195}. Note=Localized at the plasma membrane
CC when associated with SLC7A5 or SLC7A8. Localized to the apical membrane
CC of placental syncytiotrophoblastic cells. Recruited to lysosomes by
CC LAPTM4B (By similarity). Located selectively at cell-cell adhesion
CC sites (By similarity). Colocalized with SLC7A8/LAT2 at the basolateral
CC membrane of kidney proximal tubules and small intestine epithelia.
CC Expressed in both luminal and abluminal membranes of brain capillary
CC endothelial cells (PubMed:11095508). {ECO:0000250,
CC ECO:0000250|UniProtKB:P08195, ECO:0000269|PubMed:11095508}.
CC -!- TISSUE SPECIFICITY: In brain expressed on capillary endothelia in
CC cerebral cortex (at protein level) (PubMed:11095508). Highest
CC expression in kidney, jejunum, ileum, colon, placenta, testis and
CC spleen. Lower levels found in liver, lung and brain with weakest
CC expression in heart. Expressed in retina, inner blood-retinal barrier
CC of retina, retinal vascular endothelial cells. Also expressed in C6
CC glioma cells and in the retinal capillary endothelial cell line TR-
CC iBRB2. {ECO:0000269|PubMed:10391916, ECO:0000269|PubMed:11095508,
CC ECO:0000269|PubMed:15980244}.
CC -!- INDUCTION: Expression induced in normal hepatic cells in the presence
CC of actinomycin-D. {ECO:0000269|PubMed:15120633}.
CC -!- PTM: Phosphorylation on Ser-300 and on Ser-421 by ecto-protein kinases
CC favors heterotypic cell-cell interactions.
CC {ECO:0000250|UniProtKB:P08195}.
CC -!- SIMILARITY: Belongs to the SLC3A transporter family. {ECO:0000255}.
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DR EMBL; U59324; AAC53560.1; -; mRNA.
DR EMBL; AB015433; BAA33036.1; -; mRNA.
DR EMBL; BC061989; AAH61989.1; -; mRNA.
DR RefSeq; NP_001258018.1; NM_001271089.2.
DR AlphaFoldDB; Q794F9; -.
DR SMR; Q794F9; -.
DR BioGRID; 248392; 3.
DR IntAct; Q794F9; 2.
DR MINT; Q794F9; -.
DR STRING; 10116.ENSRNOP00000025196; -.
DR CAZy; GH13; Glycoside Hydrolase Family 13.
DR CarbonylDB; Q794F9; -.
DR GlyGen; Q794F9; 8 sites, 8 N-linked glycans (2 sites).
DR iPTMnet; Q794F9; -.
DR PhosphoSitePlus; Q794F9; -.
DR SwissPalm; Q794F9; -.
DR jPOST; Q794F9; -.
DR PaxDb; Q794F9; -.
DR PRIDE; Q794F9; -.
DR GeneID; 50567; -.
DR KEGG; rno:50567; -.
DR UCSC; RGD:3073; rat.
DR CTD; 6520; -.
DR RGD; 3073; Slc3a2.
DR eggNOG; KOG0471; Eukaryota.
DR HOGENOM; CLU_006462_9_0_1; -.
DR InParanoid; Q794F9; -.
DR PhylomeDB; Q794F9; -.
DR TreeFam; TF314498; -.
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; Q794F9; -.
DR PRO; PR:Q794F9; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q794F9; RN.
DR GO; GO:1990184; C:amino acid transport complex; ISO:RGD.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0044225; C:apical pole of neuron; ISO:RGD.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IC:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0015173; F:aromatic amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0015180; F:L-alanine 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; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEP:RGD.
DR GO; GO:1904273; P:L-alanine import across plasma membrane; ISO:RGD.
DR GO; GO:1903801; P:L-leucine import across plasma membrane; IDA:UniProtKB.
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; IMP:RGD.
DR GO; GO:0042476; P:odontogenesis; IEP:RGD.
DR GO; GO:0015823; P:phenylalanine transport; ISO:RGD.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0015827; P:tryptophan transport; ISS:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; ISO:RGD.
DR Gene3D; 2.60.40.1180; -; 1.
DR InterPro; IPR006047; Glyco_hydro_13_cat_dom.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR042280; SLC3A2.
DR InterPro; IPR031984; SLC3A2_N.
DR PANTHER; PTHR46673; PTHR46673; 1.
DR Pfam; PF00128; Alpha-amylase; 1.
DR Pfam; PF16028; SLC3A2_N; 1.
DR SMART; SM00642; Aamy; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Cell junction; Cell membrane; Disulfide bond;
KW Glycoprotein; Isopeptide bond; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT CHAIN 1..527
FT /note="4F2 cell-surface antigen heavy chain"
FT /id="PRO_0000252236"
FT TOPO_DOM 1..75
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..98
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..527
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 510
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 103
FT /note="Interchain (with C-164 in SLC7A5)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CROSSLNK 42
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
SQ SEQUENCE 527 AA; 58072 MW; CBA92D830893672B CRC64;
MSQDTEVDMK DVELNELEPE KQPMNAADGA AAGEKNGLVK IKVAEDEAEA GVKFTGLSKE
ELLKVAGSPG WVRTRWALLL LFWLGWLGML AGAVVIIVRA PRCRELPVQR WWHKGALYRI
GDLQAFVGPE ARGIAGLKNH LEYLSTLKVK GLVLGPIHKN QKDEVNETDL KQIDPDLGSQ
EDFKDLLQSA KKKSIHIILD LTPNYKGQNA WFLPPQADIV ATKMKEALSS WLQDGVDGFQ
VRDVGKLANA SLYLAEWQNI TKNFSEDRLL IAGTASSDLQ QIVNILESTS DLLLTSSYLS
QPVFTGEHAE LLVIKYLNAT GSRWCSWSVS QAGLLTSFIP AQFLRLYQLL LFTLPGTPVF
SYGDELGLQA VALPGQPMEA PFMLWNESSN SQTSSPVSLN MTVKGQNEDP GSLLTQFRRL
SDLRGKERSL LHGDFDALSS SSGLFSYVRH WDQNERYLVV LNFQDVGLSA RVGASNLPAG
ISLPASANLL LSTDSTRLSR EEGTSLSLEN LSLNPYEGLL LQFPFVA
