4F2_RABIT
ID 4F2_RABIT Reviewed; 529 AA.
AC Q7YQK3;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=4F2 cell-surface antigen heavy chain {ECO:0000250|UniProtKB:P08195};
DE Short=4F2hc {ECO:0000303|PubMed:16125134};
DE AltName: Full=Solute carrier family 3 member 2 {ECO:0000250|UniProtKB:P08195};
DE AltName: CD_antigen=CD98;
GN Name=SLC3A2 {ECO:0000250|UniProtKB:P08195};
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:AAP47190.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND INTERACTION WITH SLC7A5.
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 FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC7A5, AND MUTAGENESIS OF
RP CYS-110 AND CYS-332.
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: Component of several heterodimeric complexes involved in
CC amino acid transport (By similarity). The precise substrate specificity
CC depends on the other subunit in the heterodimer (By similarity). The
CC complexes function as amino acid exchangers (By similarity). The
CC homodimer functions as sodium-independent, high-affinity transporter
CC that mediates uptake of large neutral amino acids such as
CC phenylalanine, tyrosine, L-DOPA, leucine, histidine, methionine and
CC tryptophan (PubMed:12614332, PubMed:16125134). The heterodimer formed
CC 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 (By similarity). {ECO:0000250|UniProtKB:P08195,
CC ECO:0000250|UniProtKB:P10852, ECO:0000250|UniProtKB:Q794F9,
CC ECO:0000269|PubMed:12614332, ECO:0000269|PubMed:16125134}.
CC -!- SUBUNIT: Disulfide-linked heterodimer with a non-glycosylated light
CC chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11)
CC (PubMed:12614332, PubMed:16125134). 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:12614332,
CC ECO:0000269|PubMed:16125134}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P08195}. Cell membrane
CC {ECO:0000269|PubMed:12614332, ECO:0000269|PubMed:16125134}; 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 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P08195}.
CC -!- PTM: Phosphorylation on Ser-307 or Ser-309 and on Ser-426 by ecto-
CC protein kinases favors heterotypic cell-cell interactions.
CC {ECO:0000250|UniProtKB:P08195}.
CC -!- SIMILARITY: Belongs to the SLC3A transporter family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP47190.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF515773; AAP47190.1; ALT_INIT; mRNA.
DR RefSeq; NP_001076125.1; NM_001082656.1.
DR AlphaFoldDB; Q7YQK3; -.
DR SMR; Q7YQK3; -.
DR STRING; 9986.ENSOCUP00000001148; -.
DR CAZy; GH13; Glycoside Hydrolase Family 13.
DR GeneID; 100009363; -.
DR KEGG; ocu:100009363; -.
DR CTD; 6520; -.
DR eggNOG; KOG0471; Eukaryota.
DR InParanoid; Q7YQK3; -.
DR OrthoDB; 1384693at2759; -.
DR TreeFam; TF314498; -.
DR SABIO-RK; Q7YQK3; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IC:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:1903801; P:L-leucine import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0015820; P:leucine transport; ISS:UniProtKB.
DR GO; GO:0015827; P:tryptophan transport; IDA:UniProtKB.
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..529
FT /note="4F2 cell-surface antigen heavy chain"
FT /id="PRO_0000252235"
FT TOPO_DOM 1..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 106..529
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..20
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:0000250|UniProtKB:P08195"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q794F9"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110
FT /note="Interchain (with C-164 in SLC7A5)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CROSSLNK 49
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT CROSSLNK 66
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P08195"
FT MUTAGEN 110
FT /note="C->S: No effect on phenylalanine transport."
FT /evidence="ECO:0000269|PubMed:16125134"
FT MUTAGEN 332
FT /note="C->S: No effect on phenylalanine transport."
FT /evidence="ECO:0000269|PubMed:16125134"
SQ SEQUENCE 529 AA; 57795 MW; 9ACBEA22D818BF6E CRC64;
MSQDTEVDMK EVELNELEPE KQPMNAASEA AVAMAVAGGA EKNGLVKIKV AEDEAEAAAK
FTGLSKEELL KVAGSPGWVR TRWALLLLFW LGWIGMLAGA VVIIVRAPRC RELPVQRWWH
KGALYRVGDL QAFQARDSGD LAGLKGHLDY LSTLKVKGLV LGPIHKNQED DVAGTNLQEI
NPAVGSKEEF DSFLQSAKKK SIRVILDLTP NYLGQNSWFL PTQVDLVATK VKDALNFWLQ
AGVDGFQVRD VGNLTNAALH LAEWRNITKS FSEDRLLIAG TESSDLHQIL SLLESTKDLL
LTSSYLSASG VSGENMKFLV TQYLNATDSH WCSWSLSQAG LLTSFVPAQL LRLYQLLLFT
LPGTPVFSYG DEIGLQAAAL PGEPAKAPVM LWDESSLPSA SVSANMTVKG QDEDSGSLLS
LFRRLSDQRG KERSLLHGDF HALSTGSNLF SYVRHWDQNE RFLVVLNFGD ESLSARLGAS
SLPAGASLPA RADLLLSTHP GREEGTSLAL EHLNLEPHEG LLLHFPYVA
