ID   4F2_MOUSE               Reviewed;         526 AA.
AC   P10852; Q54AH5;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   25-NOV-2008, entry version 77.
DE   RecName: Full=4F2 cell-surface antigen heavy chain;
DE            Short=4F2hc;
DE   AltName: CD_antigen=CD98;
GN   Name=Slc3a2; Synonyms=Mdu1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC   STRAIN=C57BL/6 X DBA/2, and ICR; TISSUE=Macrophage, and Pre-B cell;
RX   MEDLINE=89183602; PubMed=2928113; DOI=10.1093/nar/17.5.1915;
RA   Parmacek M.S., Karpinski B.A., Gottsdiener K.M., Thompson C.B.,
RA   Leiden J.M.;
RT   "Structure, expression and regulation of the murine 4F2 heavy chain.";
RL   Nucleic Acids Res. 17:1915-1931(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=ICR; TISSUE=Brain;
RA   Kanai Y., Watanabe M., Endou H.;
RT   "Localization of expression of system L neutral amino acid transporter
RT   LAT1 in brain.";
RL   Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney, and Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6; TISSUE=Brain;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 43-53; 163-171; 456-463 AND 488-496, AND MASS
RP   SPECTROMETRY.
RC   STRAIN=C57BL/6; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [6]
RP   FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   DEVELOPMENTAL STAGE, INDUCTION, AND MUTAGENESIS OF CYS-103.
RC   STRAIN=BALB/c;
RX   MEDLINE=99115648; PubMed=9915839; DOI=10.1074/jbc.274.5.3009;
RA   Nakamura E., Sato M., Yang H., Miyagawa F., Harasaki M., Tomita K.,
RA   Matsuoka S., Noma A., Iwai K., Minato N.;
RT   "4F2 (CD98) heavy chain is associated covalently with an amino acid
RT   transporter and controls intracellular trafficking and membrane
RT   topology of 4F2 heterodimer.";
RL   J. Biol. Chem. 274:3009-3016(1999).
RN   [7]
RP   FUNCTION, AND SUBUNIT.
RX   MEDLINE=99321901; PubMed=10391915; DOI=10.1074/jbc.274.28.19738;
RA   Pineda M., Fernandez E., Torrents D., Estevez R., Lopez C., Camps M.,
RA   Lloberas J., Zorzano A., Palacin M.;
RT   "Identification of a membrane protein, LAT-2, that co-expresses with
RT   4F2 heavy chain, an L-type amino acid transport activity with broad
RT   specificity for small and large zwitterionic amino acids.";
RL   J. Biol. Chem. 274:19738-19744(1999).
RN   [8]
RP   SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   MEDLINE=20044753; PubMed=10574970; DOI=10.1074/jbc.274.49.34948;
RA   Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F.,
RA   Kuehn L.C.;
RT   "LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter
RT   of kidney and intestine.";
RL   J. Biol. Chem. 274:34948-34954(1999).
RN   [9]
RP   FUNCTION.
RX   PubMed=11011012; DOI=10.1016/S0006-8993(00)02758-X;
RA   Kageyama T., Nakamura M., Matsuo A., Yamasaki Y., Takakura Y.,
RA   Hashida M., Kanai Y., Naito M., Tsuruo T., Minato N., Shimohama S.;
RT   "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain
RT   barrier.";
RL   Brain Res. 879:115-121(2000).
CC   -!- FUNCTION: Required for the function of light chain amino-acid
CC       transporters. Involved in sodium-independent, high-affinity
CC       transport of large neutral amino acids such as phenylalanine,
CC       tyrosine, leucine, arginine and tryptophan. Involved in guiding
CC       and targeting of LAT1 and LAT2 to the plasma membrane. When
CC       associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine
CC       exchanger, following an antiport mechanism for amino acid
CC       transport, influencing arginine release in exchange for
CC       extracellular amino acids. Plays a role in nitric oxide synthesis
CC       in human umbilical vein endothelial cells (HUVECs) via transport
CC       of L-arginine. Required for normal and neoplastic cell growth.
CC       When associated with SLC7A5/LAT1, is also involved in the
CC       transport of L-DOPA across the blood-brain barrier, and that of
CC       thyroid hormones triiodothyronine (T3) and thyroxine (T4) across
CC       the cell membrane in tissues such as placenta. Involved in the
CC       uptake of methylmercury (MeHg) when administered as the L-cysteine
CC       or D,L-homocysteine complexes, and hence plays a role in metal ion
CC       homeostasis and toxicity. When associated with SLC7A5 or SLC7A8,
CC       involved in the cellular activity of small molecular weight
CC       nitrosothiols, via the stereoselective transport of L-
CC       nitrosocysteine (L-CNSO) across the transmembrane. Together with
CC       ICAM1, regulates the transport activity LAT2 in polarized
CC       intestinal cells, by generating and delivering intracellular
CC       signals. When associated with SLC7A5, plays an important role in
CC       transporting L-leucine from the circulating blood to the retina
CC       across the inner blood-retinal barrier.
CC   -!- SUBUNIT: Disulfide-linked heterodimer of a glycosylated heavy
CC       chain and a non-glycosylated light chain (SLC7A5, SLC7A6 or
CC       SLC7A8). Colocalizes with cadherins (By similarity). Interacts
CC       with FAM57A/CT120 and ICAM1 (By similarity). Constitutively and
CC       specifically associates with beta-1 integrins (alpha-2/beta-1,
CC       alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), but minimally
CC       with alpha-4/beta-1 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane; Single-pass type II
CC       membrane protein. Melanosome (By similarity). Note=Identified by
CC       mass spectrometry in melanosome fractions from stage I to stage IV
CC       (By similarity). Localized to the plasma membrane when associated
CC       with SLC7A5 or SLC7A8 (By similarity). Localized to the placental
CC       apical membrane (By similarity). Located selectively at cell-cell
CC       adhesion sites. 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
CC       capillary endothelial cells (By similarity).
CC   -!- TISSUE SPECIFICITY: Observed in all adult tissues tested with
CC       strongest expression in kidney, small intestine, spleen, thymus
CC       and liver. Moderate expression in brain, stomach, heart, testis,
CC       lung, skin, pancreas and skeletal muscle. Expressed on the surface
CC       of epithelial cells of most embryonic tissues including epidermis,
CC       choroid plexus in the brain, retina, as well as intestinal, renal,
CC       and thymic epithelium. In brain expressed on capillary endothelia
CC       in cerebral cortex.
CC   -!- DEVELOPMENTAL STAGE: Strong expression in the liver of 14 dpc
CC       embryo and in brain, spleen, liver, kidney and intestine of an 18
CC       dpc embryo.
CC   -!- INDUCTION: Expression induced by concanavilin-A stimulation.
CC       Induced during cell activation but is subsequently maintained at
CC       constant levels throughout the cell cycle in exponentially growing
CC       cells.
CC   -!- MISCELLANEOUS: Leucine uptake was inhibited by ileum, valine
CC       histidine and phenylalanine as well as by 2-aminobicyclo-(2,2,1)-
CC       heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L
CC       transport).
CC   -!- SIMILARITY: Belongs to the SLC3A transporter family.
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DR   EMBL; X14309; CAA32490.1; -; mRNA.
DR   EMBL; AB023408; BAA90555.1; -; mRNA.
DR   EMBL; AK161280; BAE36291.1; -; mRNA.
DR   EMBL; AK165417; BAE38172.1; -; mRNA.
DR   EMBL; BC065173; AAH65173.1; -; mRNA.
DR   PIR; S03600; S03600.
DR   UniGene; Mm.4114; -.
DR   PhosphoSite; P10852; -.
DR   Ensembl; ENSMUSG00000010095; Mus musculus.
DR   MGI; MGI:96955; Slc3a2.
DR   HOVERGEN; P10852; -.
DR   ArrayExpress; P10852; -.
DR   GermOnline; ENSMUSG00000010095; Mus musculus.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR   GO; GO:0043169; F:cation binding; IEA:InterPro.
DR   GO; GO:0005515; F:protein binding; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0015827; P:tryptophan transport; ISS:UniProtKB.
DR   InterPro; IPR006047; Glyco_hydro_13_cat.
DR   InterPro; IPR013781; Glyco_hydro_sub_cat.
DR   Gene3D; G3DSA:3.20.20.80; Glyco_hydro_cat; 1.
DR   Pfam; PF00128; Alpha-amylase; 1.
PE   1: Evidence at protein level;
KW   Amino-acid transport; Cell membrane; Direct protein sequencing;
KW   Glycoprotein; Membrane; Phosphoprotein; Signal-anchor; Transmembrane;
KW   Transport.
FT   CHAIN         1    526       4F2 cell-surface antigen heavy chain.
FT                                /FTId=PRO_0000064384.
FT   TOPO_DOM      1     75       Cytoplasmic (Potential).
FT   TRANSMEM     76     99       Signal-anchor for type II membrane
FT                                protein.
FT   TOPO_DOM    100    526       Extracellular (Potential).
FT   MOD_RES       2      2       Phosphoserine (By similarity).
FT   MOD_RES       5      5       Phosphothreonine (By similarity).
FT   CARBOHYD    166    166       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    259    259       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    263    263       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    301    301       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    318    318       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    385    385       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    399    399       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    509    509       N-linked (GlcNAc...) (Potential).
FT   DISULFID    103    103       Interchain (with light chain) (Probable).
FT   MUTAGEN     103    103       C->S: No effect on guidance of LAT1 to
FT                                the plasma membrane.
SQ   SEQUENCE   526 AA;  58337 MW;  AE6261F11C7D9468 CRC64;
     MSQDTEVDMK DVELNELEPE KQPMNAADGA AAGEKNGLVK IKVAEDETEA GVKFTGLSKE
     ELLKVAGSPG WVRTRWALLL LFWLGWLGML AGAVVIIVRA PRCRELPVQR WWHKGALYRI
     GDLQAFVGRD AGGIAGLKSH LEYLSTLKVK GLVLGPIHKN QKDEINETDL KQINPTLGSQ
     EDFKDLLQSA KKKSIHIILD LTPNYQGQNA WFLPAQADIV ATKMKEALSS WLQDGVDGFQ
     FRDVGKLMNA PLYLAEWQNI TKNLSEDRLL IAGTESSDLQ QIVNILESTS DLLLTSSYLS
     NSTFTGERTE SLVTRFLNAT GSQWCSWSVS QAGLLADFIP DHLLRLYQLL LFTLPGTPVF
     SYGDELGLQG ALPGQPAKAP LMPWNESSIF HIPRPVSLNM TVKGQNEDPG SLLTQFRRLS
     DLRGKERSLL HGDFHALSSS PDLFSYIRHW DQNERYLVVL NFRDSGRSAR LGASNLPAGI
     SLPASAKLLL STDSARQSRE EDTSLKLENL SLNPYEGLLL QFPFVA
//