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Protein

4F2 cell-surface antigen heavy chain

Gene

SLC3A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier.15 Publications

Kineticsi

  1. KM=295 µM for glutamine (in the presence of NaCl)1 Publication
  2. KM=236 µM for leucine (in the presence of NaCl)1 Publication
  3. KM=120 µM for arginine (in the presence of NaCl)1 Publication
  4. KM=138 µM for arginine (in the absence of NaCl)1 Publication

    GO - Molecular functioni

    • calcium:sodium antiporter activity Source: UniProtKB
    • catalytic activity Source: InterPro
    • cation binding Source: InterPro
    • double-stranded RNA binding Source: MGI
    • neutral amino acid transmembrane transporter activity Source: UniProtKB
    • poly(A) RNA binding Source: UniProtKB

    GO - Biological processi

    • amino acid transport Source: UniProtKB
    • blood coagulation Source: Reactome
    • calcium ion transport Source: UniProtKB
    • carbohydrate metabolic process Source: InterPro
    • cell growth Source: UniProtKB
    • ion transport Source: Reactome
    • leucine import Source: UniProtKB
    • leukocyte migration Source: Reactome
    • response to exogenous dsRNA Source: MGI
    • sodium ion transmembrane transport Source: GOC
    • transmembrane transport Source: Reactome
    • tryptophan transport Source: UniProtKB
    Complete GO annotation...

    Keywords - Biological processi

    Amino-acid transport, Transport

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000168003-MONOMER.
    ReactomeiREACT_12560. Basigin interactions.
    REACT_13796. Amino acid transport across the plasma membrane.
    SABIO-RKP08195.

    Protein family/group databases

    CAZyiGH13. Glycoside Hydrolase Family 13.
    TCDBi8.A.9.2.2. the rbat transport accessory protein (rbat) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4F2 cell-surface antigen heavy chain
    Short name:
    4F2hc
    Alternative name(s):
    4F2 heavy chain antigen
    Lymphocyte activation antigen 4F2 large subunit
    Solute carrier family 3 member 2
    CD_antigen: CD98
    Gene namesi
    Name:SLC3A2
    Synonyms:MDU1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:11026. SLC3A2.

    Subcellular locationi

    • Apical cell membrane; Single-pass type II membrane protein
    • Melanosome

    • Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Localized to the plasma membrane when associated with SLC7A5 or SLC7A8. Localized to the placental apical membrane. Located selectively at cell-cell adhesion sites (By similarity). Colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells (By similarity).By similarity

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini102 – 18483CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei185 – 20521Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST
    Topological domaini206 – 630425ExtracellularSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • apical plasma membrane Source: UniProtKB-SubCell
    • cell surface Source: UniProtKB
    • cytoplasm Source: HPA
    • extracellular exosome Source: UniProtKB
    • integral component of membrane Source: UniProtKB
    • melanosome Source: UniProtKB-SubCell
    • membrane Source: UniProtKB
    • nucleoplasm Source: HPA
    • nucleus Source: HPA
    • plasma membrane Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi210 – 2101C → S: Abolishes dimerization, leucine uptake and interaction with beta-1 integrins. 3 Publications
    Mutagenesisi431 – 4311C → S: No effect on dimerization, leucine uptake or interaction with beta-1 integrins. 2 Publications

    Organism-specific databases

    PharmGKBiPA35894.

    Polymorphism and mutation databases

    BioMutaiSLC3A2.
    DMDMi257051063.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 6306304F2 cell-surface antigen heavy chainPRO_0000064383Add
    BLAST
    Isoform 2 (identifier: P08195-2)
    Initiator methioninei1 – 11Removed3 Publications

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine2 Publications
    Cross-linki147 – 147Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
    Modified residuei165 – 1651Phosphoserine1 Publication
    Disulfide bondi210 – 210Interchain (with light chain)1 Publication
    Glycosylationi365 – 3651N-linked (GlcNAc...)3 Publications
    Glycosylationi381 – 3811N-linked (GlcNAc...)4 Publications
    Modified residuei406 – 4061Phosphoserine1 Publication
    Modified residuei408 – 4081Phosphoserine1 Publication
    Modified residuei410 – 4101Phosphoserine1 Publication
    Glycosylationi424 – 4241N-linked (GlcNAc...) (complex)4 Publications
    Glycosylationi506 – 5061N-linked (GlcNAc...)2 Publications
    Modified residuei527 – 5271Phosphoserine1 Publication
    Modified residuei531 – 5311Phosphoserine1 Publication
    Isoform 2 (identifier: P08195-2)
    Modified residuei2 – 21N-acetylserine3 Publications
    Modified residuei2 – 21Phosphoserine3 Publications

    Post-translational modificationi

    Phosphorylation on Ser-406; Ser-408 or Ser-410 and on Ser-527 or Ser-531 by ecto-protein kinases favors heterotypic cell-cell interactions.1 Publication

    Keywords - PTMi

    Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP08195.
    PaxDbiP08195.
    PRIDEiP08195.

    PTM databases

    PhosphoSiteiP08195.

    Expressioni

    Tissue specificityi

    Expressed ubiquitously in all tissues tested with highest levels detected in kidney, placenta and testis and weakest level in thymus. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Expressed in HUVECS and at low levels in resting peripheral blood T-lymphocytes and quiescent fibroblasts. Also expressed in fetal liver and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line C2BBe1.9 Publications

    Inductioni

    Expression is induced in resting peripheral blood T-lymphocytes following PHA stimulation. Expression increases at the time of maximal DNA synthesis, in fibroblasts stimulated to divide. Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore.3 Publications

    Gene expression databases

    BgeeiP08195.
    CleanExiHS_SLC3A2.
    ExpressionAtlasiP08195. baseline and differential.
    GenevisibleiP08195. HS.

    Organism-specific databases

    HPAiCAB010455.
    HPA017980.

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer of a glycosylated heavy chain and a non-glycosylated light chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11). Colocalizes with cadherins (By similarity). Interacts with FAM57A/CT120 and ICAM1. Constitutively and specifically associates with beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), but minimally with alpha-4/beta-1.By similarity14 Publications

    Protein-protein interaction databases

    BioGridi112411. 28 interactions.
    IntActiP08195. 11 interactions.
    MINTiMINT-4999018.
    STRINGi9606.ENSP00000367123.

    Structurei

    Secondary structure

    1
    630
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi218 – 2203Combined sources
    Beta strandi224 – 2274Combined sources
    Helixi230 – 2345Combined sources
    Helixi241 – 2455Combined sources
    Helixi248 – 2536Combined sources
    Beta strandi257 – 2615Combined sources
    Beta strandi265 – 2673Combined sources
    Beta strandi275 – 2806Combined sources
    Helixi282 – 2843Combined sources
    Helixi287 – 29913Combined sources
    Beta strandi303 – 3075Combined sources
    Turni310 – 3134Combined sources
    Beta strandi314 – 3163Combined sources
    Beta strandi319 – 3213Combined sources
    Helixi323 – 34018Combined sources
    Beta strandi344 – 3474Combined sources
    Helixi350 – 3523Combined sources
    Helixi356 – 37015Combined sources
    Beta strandi375 – 3795Combined sources
    Helixi385 – 3917Combined sources
    Turni392 – 3943Combined sources
    Beta strandi399 – 4013Combined sources
    Turni404 – 4074Combined sources
    Helixi412 – 42615Combined sources
    Beta strandi437 – 4393Combined sources
    Helixi441 – 4433Combined sources
    Helixi447 – 4493Combined sources
    Helixi450 – 4578Combined sources
    Beta strandi460 – 4678Combined sources
    Helixi470 – 4723Combined sources
    Helixi476 – 4783Combined sources
    Beta strandi479 – 4813Combined sources
    Beta strandi484 – 4863Combined sources
    Helixi493 – 4953Combined sources
    Helixi500 – 5023Combined sources
    Helixi505 – 5073Combined sources
    Helixi509 – 5135Combined sources
    Helixi519 – 53214Combined sources
    Helixi534 – 5385Combined sources
    Beta strandi540 – 5456Combined sources
    Beta strandi550 – 5567Combined sources
    Beta strandi562 – 5687Combined sources
    Beta strandi570 – 5723Combined sources
    Beta strandi581 – 5833Combined sources
    Helixi585 – 5873Combined sources
    Beta strandi591 – 60313Combined sources
    Beta strandi607 – 6104Combined sources
    Helixi611 – 6133Combined sources
    Beta strandi621 – 6266Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DH2X-ray2.10A212-630[»]
    2DH3X-ray2.80A/B212-630[»]
    ProteinModelPortaliP08195.
    SMRiP08195. Positions 212-630.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08195.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the SLC3A transporter family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0366.
    GeneTreeiENSGT00530000063127.
    HOGENOMiHOG000233529.
    HOVERGENiHBG000023.
    InParanoidiP08195.
    KOiK06519.
    OrthoDBiEOG7ZSHSV.
    PhylomeDBiP08195.

    Family and domain databases

    Gene3Di2.60.40.1180. 1 hit.
    3.20.20.80. 1 hit.
    InterProiIPR015902. Glyco_hydro_13.
    IPR013780. Glyco_hydro_13_b.
    IPR006047. Glyco_hydro_13_cat_dom.
    IPR013781. Glyco_hydro_catalytic_dom.
    IPR017853. Glycoside_hydrolase_SF.
    [Graphical view]
    PANTHERiPTHR10357. PTHR10357. 1 hit.
    PfamiPF00128. Alpha-amylase. 2 hits.
    [Graphical view]
    SUPFAMiSSF51445. SSF51445. 1 hit.

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P08195-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE
    60 70 80 90 100
    LLASGDPLPS ASQNAEMIET GSDCVTQAGL QLLASSDPPA LASKNAEVTG
    110 120 130 140 150
    TMSQDTEVDM KEVELNELEP EKQPMNAASG AAMSLAGAEK NGLVKIKVAE
    160 170 180 190 200
    DEAEAAAAAK FTGLSKEELL KVAGSPGWVR TRWALLLLFW LGWLGMLAGA
    210 220 230 240 250
    VVIIVRAPRC RELPAQKWWH TGALYRIGDL QAFQGHGAGN LAGLKGRLDY
    260 270 280 290 300
    LSSLKVKGLV LGPIHKNQKD DVAQTDLLQI DPNFGSKEDF DSLLQSAKKK
    310 320 330 340 350
    SIRVILDLTP NYRGENSWFS TQVDTVATKV KDALEFWLQA GVDGFQVRDI
    360 370 380 390 400
    ENLKDASSFL AEWQNITKGF SEDRLLIAGT NSSDLQQILS LLESNKDLLL
    410 420 430 440 450
    TSSYLSDSGS TGEHTKSLVT QYLNATGNRW CSWSLSQARL LTSFLPAQLL
    460 470 480 490 500
    RLYQLMLFTL PGTPVFSYGD EIGLDAAALP GQPMEAPVML WDESSFPDIP
    510 520 530 540 550
    GAVSANMTVK GQSEDPGSLL SLFRRLSDQR SKERSLLHGD FHAFSAGPGL
    560 570 580 590 600
    FSYIRHWDQN ERFLVVLNFG DVGLSAGLQA SDLPASASLP AKADLLLSTQ
    610 620 630
    PGREEGSPLE LERLKLEPHE GLLLRFPYAA
    Length:630
    Mass (Da):67,994
    Last modified:September 1, 2009 - v3
    Checksum:iAE427F8204CC10B0
    GO
    Isoform 2 (identifier: P08195-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-101: Missing.

    Show »
    Length:529
    Mass (Da):57,945
    Checksum:i82F26856737E8F31
    GO
    Isoform 3 (identifier: P08195-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         38-99: Missing.

    Show »
    Length:568
    Mass (Da):61,816
    Checksum:iF2B9400F95F2E1BD
    GO
    Isoform 4 (identifier: P08195-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         98-98: V → VTETGFHHVSQADIEFLTSIDPTASASGSAGI

    Show »
    Length:661
    Mass (Da):71,123
    Checksum:i06C2CDFD6B1D93F5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti137 – 1371G → E in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti158 – 1581A → P in AAA51540 (PubMed:3036867).Curated
    Sequence conflicti223 – 2231A → P in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti315 – 3151E → D in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti320 – 3201S → F in AAA35489 (PubMed:3265470).Curated
    Sequence conflicti372 – 3721E → G in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti412 – 4132GE → PQ in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti465 – 4651V → L in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti481 – 4811G → P in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti549 – 5491G → E in AAA35489 (PubMed:3265470).Curated
    Sequence conflicti609 – 6091L → P in AAA35536 (PubMed:3480538).Curated
    Sequence conflicti612 – 6121E → G in AAA35536 (PubMed:3480538).Curated

    Mass spectrometryi

    Molecular mass is 57944.93 Da from positions 1 - 529. Determined by MALDI. 1 Publication

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 101101Missing in isoform 2. 4 PublicationsVSP_037907Add
    BLAST
    Alternative sequencei38 – 9962Missing in isoform 3. 1 PublicationVSP_037908Add
    BLAST
    Alternative sequencei98 – 981V → VTETGFHHVSQADIEFLTSI DPTASASGSAGI in isoform 4. 1 PublicationVSP_037909

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02939 mRNA. Translation: AAA52497.1.
    J02769 mRNA. Translation: AAA51540.1.
    J03569 mRNA. Translation: AAA35536.1.
    M21904
    , M21898, M21899, M21900, M21901, M21902, M21903 Genomic DNA. Translation: AAA35489.1.
    AB018010 mRNA. Translation: BAA84649.1.
    AP001160 Genomic DNA. No translation available.
    BC001061 mRNA. Translation: AAH01061.2.
    BC003000 mRNA. Translation: AAH03000.2.
    BE794697 mRNA. No translation available.
    CCDSiCCDS31589.1. [P08195-3]
    CCDS31590.1. [P08195-2]
    CCDS8039.2. [P08195-1]
    PIRiA28455. SAHU4F.
    RefSeqiNP_001012680.1. NM_001012662.2.
    NP_001012682.1. NM_001012664.2. [P08195-3]
    NP_001013269.1. NM_001013251.2. [P08195-2]
    NP_002385.3. NM_002394.5. [P08195-1]
    UniGeneiHs.502769.

    Genome annotation databases

    EnsembliENST00000338663; ENSP00000340815; ENSG00000168003. [P08195-2]
    ENST00000377889; ENSP00000367121; ENSG00000168003. [P08195-3]
    ENST00000377890; ENSP00000367122; ENSG00000168003.
    GeneIDi6520.
    KEGGihsa:6520.
    UCSCiuc001nwd.3. human. [P08195-1]
    uc001nwf.3. human. [P08195-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02939 mRNA. Translation: AAA52497.1.
    J02769 mRNA. Translation: AAA51540.1.
    J03569 mRNA. Translation: AAA35536.1.
    M21904
    , M21898, M21899, M21900, M21901, M21902, M21903 Genomic DNA. Translation: AAA35489.1.
    AB018010 mRNA. Translation: BAA84649.1.
    AP001160 Genomic DNA. No translation available.
    BC001061 mRNA. Translation: AAH01061.2.
    BC003000 mRNA. Translation: AAH03000.2.
    BE794697 mRNA. No translation available.
    CCDSiCCDS31589.1. [P08195-3]
    CCDS31590.1. [P08195-2]
    CCDS8039.2. [P08195-1]
    PIRiA28455. SAHU4F.
    RefSeqiNP_001012680.1. NM_001012662.2.
    NP_001012682.1. NM_001012664.2. [P08195-3]
    NP_001013269.1. NM_001013251.2. [P08195-2]
    NP_002385.3. NM_002394.5. [P08195-1]
    UniGeneiHs.502769.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DH2X-ray2.10A212-630[»]
    2DH3X-ray2.80A/B212-630[»]
    ProteinModelPortaliP08195.
    SMRiP08195. Positions 212-630.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112411. 28 interactions.
    IntActiP08195. 11 interactions.
    MINTiMINT-4999018.
    STRINGi9606.ENSP00000367123.

    Protein family/group databases

    CAZyiGH13. Glycoside Hydrolase Family 13.
    TCDBi8.A.9.2.2. the rbat transport accessory protein (rbat) family.

    PTM databases

    PhosphoSiteiP08195.

    Polymorphism and mutation databases

    BioMutaiSLC3A2.
    DMDMi257051063.

    Proteomic databases

    MaxQBiP08195.
    PaxDbiP08195.
    PRIDEiP08195.

    Protocols and materials databases

    DNASUi6520.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000338663; ENSP00000340815; ENSG00000168003. [P08195-2]
    ENST00000377889; ENSP00000367121; ENSG00000168003. [P08195-3]
    ENST00000377890; ENSP00000367122; ENSG00000168003.
    GeneIDi6520.
    KEGGihsa:6520.
    UCSCiuc001nwd.3. human. [P08195-1]
    uc001nwf.3. human. [P08195-3]

    Organism-specific databases

    CTDi6520.
    GeneCardsiGC11P062623.
    HGNCiHGNC:11026. SLC3A2.
    HPAiCAB010455.
    HPA017980.
    MIMi158070. gene.
    neXtProtiNX_P08195.
    PharmGKBiPA35894.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0366.
    GeneTreeiENSGT00530000063127.
    HOGENOMiHOG000233529.
    HOVERGENiHBG000023.
    InParanoidiP08195.
    KOiK06519.
    OrthoDBiEOG7ZSHSV.
    PhylomeDBiP08195.

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000168003-MONOMER.
    ReactomeiREACT_12560. Basigin interactions.
    REACT_13796. Amino acid transport across the plasma membrane.
    SABIO-RKP08195.

    Miscellaneous databases

    ChiTaRSiSLC3A2. human.
    EvolutionaryTraceiP08195.
    GeneWikiiSLC3A2.
    GenomeRNAii6520.
    NextBioi25353.
    PROiP08195.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP08195.
    CleanExiHS_SLC3A2.
    ExpressionAtlasiP08195. baseline and differential.
    GenevisibleiP08195. HS.

    Family and domain databases

    Gene3Di2.60.40.1180. 1 hit.
    3.20.20.80. 1 hit.
    InterProiIPR015902. Glyco_hydro_13.
    IPR013780. Glyco_hydro_13_b.
    IPR006047. Glyco_hydro_13_cat_dom.
    IPR013781. Glyco_hydro_catalytic_dom.
    IPR017853. Glycoside_hydrolase_SF.
    [Graphical view]
    PANTHERiPTHR10357. PTHR10357. 1 hit.
    PfamiPF00128. Alpha-amylase. 2 hits.
    [Graphical view]
    SUPFAMiSSF51445. SSF51445. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth."
      Quackenbush E., Clabby M., Gottesdiener K.M., Barbosa J., Jones N.H., Strominger J.L., Speck S., Leiden J.M.
      Proc. Natl. Acad. Sci. U.S.A. 84:6526-6530(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    2. Erratum
      Quackenbush E., Clabby M., Gottesdiener K.M., Barbosa J., Jones N.H., Strominger J.L., Speck S., Leiden J.M.
      Proc. Natl. Acad. Sci. U.S.A. 84:8618-8618(1987)
      Cited for: SEQUENCE REVISION.
    3. "Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus."
      Teixeira S., di Grandi S., Kuehn L.C.
      J. Biol. Chem. 262:9574-9580(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    4. "Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2."
      Lumadue J.A., Glick A.B., Ruddle F.H.
      Proc. Natl. Acad. Sci. U.S.A. 84:9204-9208(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INDUCTION.
      Tissue: Fibroblast.
    5. "Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation."
      Gottesdiener K.M., Karpinski B.A., Lindsten T., Strominger J.L., Jones N.H., Thompson C.B., Leiden J.M.
      Mol. Cell. Biol. 8:3809-3819(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY, INDUCTION.
    6. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
      Tissue: Placenta.
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 4).
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
      Tissue: Lung and Placenta.
    9. Bienvenut W.V., Lao L., Ryan K.L.
      Submitted (OCT-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 1-17; 146-171; 227-245; 304-313; 440-451; 511-525 AND 593-630, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Cervix carcinoma.
    10. Strausberg R.L.
      Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 83-209 (ISOFORM 4).
      Tissue: Lung carcinoma.
    11. Bienvenut W.V.
      Submitted (MAR-2005) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 112-122; 148-160; 227-245; 248-255; 288-298; 304-313; 440-451; 511-524 AND 593-625, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: B-cell lymphoma.
    12. "Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance."
      Torrents D., Estevez R., Pineda M., Fernandez E., Lloberas J., Shi Y.-B., Zorzano A., Palacin M.
      J. Biol. Chem. 273:32437-32445(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, INHIBITION, MUTAGENESIS OF CYS-210 AND CYS-431.
    13. "Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family."
      Mastroberardino L., Spindler B., Pfeiffer R., Skelly P.J., Loffing J., Shoemaker C.B., Verrey F.
      Nature 395:288-291(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    14. "Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family."
      Pfeiffer R., Rossier G., Spindler B., Meier C., Kuehn L.C., Verrey F.
      EMBO J. 18:49-57(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    15. "The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine."
      Broeer A., Wagner C.A., Lang F., Broeer S.
      Biochem. J. 349:787-795(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    16. "Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains."
      Broeer A., Friedrich B., Wagner C.A., Fillon S., Ganapathy V., Lang F., Broeer S.
      Biochem. J. 355:725-731(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
    17. "Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta."
      Ritchie J.W.A., Taylor P.M.
      Biochem. J. 356:719-725(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    18. "Beta1 integrins show specific association with CD98 protein in low density membranes."
      Kolesnikova T.V., Mannion B.A., Berditchevski F., Hemler M.E.
      BMC Biochem. 2:10-10(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, INTERACTION WITH BETA-1 INTEGRINS, MUTAGENESIS OF CYS-210 AND CYS-431.
    19. "Thyroid hormone transport by the heterodimeric human system L amino acid transporter."
      Friesema E.C.H., Docter R., Moerings E.P.C.M., Verrey F., Krenning E.P., Hennemann G., Visser T.J.
      Endocrinology 142:4339-4348(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    20. "Expression and regulation of 4F2hc and hLAT1 in human trophoblasts."
      Okamoto Y., Sakata M., Ogura K., Yamamoto T., Yamaguchi M., Tasaka K., Kurachi H., Tsurudome M., Murata Y.
      Am. J. Physiol. 282:C196-C204(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
    21. "Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism."
      He X.H., Di Y., Li J., Xie Y., Tang Y., Zhang F., Wei L., Zhang Y., Qin W.X., Huo K., Li Y., Wan D.F., Gu J.R.
      Biochem. Biophys. Res. Commun. 297:528-536(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FAM57A/CT120.
    22. "Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2."
      Simmons-Willis T.A., Koh A.S., Clarkson T.W., Ballatori N.
      Biochem. J. 367:239-246(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    23. "Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells."
      Kim D.K., Kanai Y., Choi H.W., Tangtrongsup S., Chairoungdua A., Babu E., Tachampa K., Anzai N., Iribe Y., Endou H.
      Biochim. Biophys. Acta 1565:112-121(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
    24. "Cluster analysis of an extensive human breast cancer cell line protein expression map database."
      Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
      Proteomics 2:212-223(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: MASS SPECTROMETRY.
      Tissue: Mammary cancer.
    25. "Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium."
      Arancibia-Garavilla Y., Toledo F., Casanello P., Sobrevia L.
      Exp. Physiol. 88:699-710(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
    26. "CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia."
      Liu X., Charrier L., Gewirtz A., Sitaraman S., Merlin D.
      J. Biol. Chem. 278:23672-23677(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, INTERACTION WITH ICAM1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    27. "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
      Zhang H., Li X.-J., Martin D.B., Aebersold R.
      Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-365; ASN-381 AND ASN-424.
    28. "L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier."
      Tomi M., Mori M., Tachikawa M., Katayama K., Terasaki T., Hosoya K.
      Invest. Ophthalmol. Vis. Sci. 46:2522-2530(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    29. "Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols."
      Li S., Whorton A.R.
      J. Biol. Chem. 280:20102-20110(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    30. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
      Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
      J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-381 AND ASN-424.
      Tissue: Plasma.
    31. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    32. "L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors."
      Nawashiro H., Otani N., Shinomiya N., Fukui S., Ooigawa H., Shima K., Matsuo H., Kanai Y., Endou H.
      Int. J. Cancer 119:484-492(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    33. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Tissue: Melanoma.
    34. "Ecto-phosphorylation of CD98 regulates cell-cell interactions."
      Nguyen H.T.T., Dalmasso G., Yan Y., Obertone T.S., Sitaraman S.V., Merlin D.
      PLoS ONE 3:E3895-E3895(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-406; SER-408; SER-410; SER-527 AND SER-531.
    35. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2).
    36. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-365; ASN-381 AND ASN-506.
      Tissue: Liver.
    37. Cited for: GLYCOSYLATION AT ASN-424.
    38. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
      Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
      Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-365; ASN-381; ASN-424 AND ASN-506.
      Tissue: Leukemic T-cell.
    39. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    40. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    41. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2).
    42. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2).
    43. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    44. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    45. "The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane."
      Fort J., de la Ballina L.R., Burghardt H.E., Ferrer-Costa C., Turnay J., Ferrer-Orta C., Uson I., Zorzano A., Fernandez-Recio J., Orozco M., Lizarbe M.A., Fita I., Palacin M.
      J. Biol. Chem. 282:31444-31452(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 212-630, SUBUNIT, MUTAGENESIS OF CYS-210, SUBCELLULAR LOCATION, DISULFIDE BOND.

    Entry informationi

    Entry namei4F2_HUMAN
    AccessioniPrimary (citable) accession number: P08195
    Secondary accession number(s): Q13543
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: September 1, 2009
    Last modified: July 22, 2015
    This is version 179 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Arginine uptake is inhibited by increasing concentrations of leucine in the presence of Na+.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.