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P10852 (4F2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
4F2 cell-surface antigen heavy chain

Short name=4F2hc
Alternative name(s):
Solute carrier family 3 member 2
CD_antigen=CD98
Gene names
Name:Slc3a2
Synonyms:Mdu1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length526 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.11

Subunit structure

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 By similarity. 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 similarity. Ref.8 Ref.9 Ref.10

Subcellular location

Apical cell membrane; Single-pass type II membrane protein. Melanosome By similarity. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV By similarity. Localized to the plasma membrane when associated with SLC7A5 or SLC7A8 By similarity. Localized to the placental apical membrane By similarity. Located selectively at cell-cell adhesion sites. 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. Ref.8 Ref.10

Tissue specificity

Observed in all adult tissues tested with strongest expression in kidney, small intestine, spleen, thymus and liver. Moderate expression in brain, stomach, heart, testis, lung, skin, pancreas and skeletal muscle. Expressed on the surface of epithelial cells of most embryonic tissues including epidermis, choroid plexus in the brain, retina, as well as intestinal, renal, and thymic epithelium. In brain expressed on capillary endothelia in cerebral cortex. Ref.1 Ref.8 Ref.10

Developmental stage

Strong expression in the liver of 14 dpc embryo and in brain, spleen, liver, kidney and intestine of an 18 dpc embryo. Ref.8

Induction

Expression induced by concanavilin-A stimulation. Induced during cell activation but is subsequently maintained at constant levels throughout the cell cycle in exponentially growing cells. Ref.1 Ref.8

Post-translational modification

Phosphorylation on Ser-300 or Ser-302 and on Ser-420 by ecto-protein kinases favors heterotypic cell-cell interactions By similarity.

Miscellaneous

Leucine uptake was inhibited by ileum, valine histidine and phenylalanine as well as by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L transport).

Sequence similarities

Belongs to the SLC3A transporter family.

Sequence caution

The sequence BAE36291.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processAmino-acid transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

leucine import

Inferred from sequence or structural similarity. Source: UniProtKB

response to exogenous dsRNA

Inferred from sequence orthology PubMed 21266579. Source: MGI

tryptophan transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncatalytic activity

Inferred from electronic annotation. Source: InterPro

cation binding

Inferred from electronic annotation. Source: InterPro

double-stranded RNA binding

Inferred from sequence orthology PubMed 21266579. Source: MGI

neutral amino acid transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10734121PubMed 23055941. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P10852-1)

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.
Isoform 2 (identifier: P10852-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDPEPTEHSTDGVSVPRQPPSAQTGLDVQVVSAAGDSGTM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5265264F2 cell-surface antigen heavy chain
PRO_0000064384

Regions

Topological domain1 – 7575Cytoplasmic Potential
Transmembrane76 – 9924Helical; Signal-anchor for type II membrane protein
Topological domain100 – 526427Extracellular Potential

Amino acid modifications

Modified residue21Phosphoserine By similarity
Modified residue581Phosphoserine Ref.12
Glycosylation1601N-linked (GlcNAc...); atypical Ref.13
Glycosylation1661N-linked (GlcNAc...) Ref.13 Ref.14
Glycosylation2491N-linked (GlcNAc...); atypical Ref.13
Glycosylation2591N-linked (GlcNAc...) Ref.13 Ref.14
Glycosylation2631N-linked (GlcNAc...) Potential
Glycosylation3011N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Potential
Glycosylation3851N-linked (GlcNAc...) Ref.13 Ref.14
Glycosylation3991N-linked (GlcNAc...) Ref.13 Ref.14
Glycosylation5091N-linked (GlcNAc...) Potential
Disulfide bond103Interchain (with light chain) Probable
Cross-link42Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence11M → MDPEPTEHSTDGVSVPRQPP SAQTGLDVQVVSAAGDSGTM in isoform 2.
VSP_054953

Experimental info

Mutagenesis1031C → S: No effect on guidance of LAT1 to the plasma membrane. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: AE6261F11C7D9468

FASTA52658,337
        10         20         30         40         50         60 
MSQDTEVDMK DVELNELEPE KQPMNAADGA AAGEKNGLVK IKVAEDETEA GVKFTGLSKE 

        70         80         90        100        110        120 
ELLKVAGSPG WVRTRWALLL LFWLGWLGML AGAVVIIVRA PRCRELPVQR WWHKGALYRI 

       130        140        150        160        170        180 
GDLQAFVGRD AGGIAGLKSH LEYLSTLKVK GLVLGPIHKN QKDEINETDL KQINPTLGSQ 

       190        200        210        220        230        240 
EDFKDLLQSA KKKSIHIILD LTPNYQGQNA WFLPAQADIV ATKMKEALSS WLQDGVDGFQ 

       250        260        270        280        290        300 
FRDVGKLMNA PLYLAEWQNI TKNLSEDRLL IAGTESSDLQ QIVNILESTS DLLLTSSYLS 

       310        320        330        340        350        360 
NSTFTGERTE SLVTRFLNAT GSQWCSWSVS QAGLLADFIP DHLLRLYQLL LFTLPGTPVF 

       370        380        390        400        410        420 
SYGDELGLQG ALPGQPAKAP LMPWNESSIF HIPRPVSLNM TVKGQNEDPG SLLTQFRRLS 

       430        440        450        460        470        480 
DLRGKERSLL HGDFHALSSS PDLFSYIRHW DQNERYLVVL NFRDSGRSAR LGASNLPAGI 

       490        500        510        520 
SLPASAKLLL STDSARQSRE EDTSLKLENL SLNPYEGLLL QFPFVA 

« Hide

Isoform 2 [UniParc].

Checksum: 7CF0572C4E948451
Show »

FASTA56562,240

References

« Hide 'large scale' references
[1]"Structure, expression and regulation of the murine 4F2 heavy chain."
Parmacek M.S., Karpinski B.A., Gottsdiener K.M., Thompson C.B., Leiden J.M.
Nucleic Acids Res. 17:1915-1931(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
Strain: C57BL/6 X DBA/2 and ICR.
Tissue: Macrophage and Pre-B cell.
[2]"Localization of expression of system L neutral amino acid transporter LAT1 in brain."
Kanai Y., Watanabe M., Endou H.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: ICR.
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
Tissue: Kidney and Testis.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Brain.
[7]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 43-53; 163-171; 456-463 AND 488-496, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6.
Tissue: Brain.
[8]"4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer."
Nakamura E., Sato M., Yang H., Miyagawa F., Harasaki M., Tomita K., Matsuoka S., Noma A., Iwai K., Minato N.
J. Biol. Chem. 274:3009-3016(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, MUTAGENESIS OF CYS-103.
Strain: BALB/c.
[9]"Identification of a membrane protein, LAT-2, that co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids."
Pineda M., Fernandez E., Torrents D., Estevez R., Lopez C., Camps M., Lloberas J., Zorzano A., Palacin M.
J. Biol. Chem. 274:19738-19744(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
[10]"LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine."
Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F., Kuehn L.C.
J. Biol. Chem. 274:34948-34954(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier."
Kageyama T., Nakamura M., Matsuo A., Yamasaki Y., Takakura Y., Hashida M., Kanai Y., Naito M., Tsuruo T., Minato N., Shimohama S.
Brain Res. 879:115-121(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation."
Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.
Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-160; ASN-166; ASN-249; ASN-259; ASN-385 AND ASN-399.
Tissue: Myoblast.
[14]"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-166; ASN-259; ASN-385 AND ASN-399.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14309 mRNA. Translation: CAA32490.1.
AB023408 mRNA. Translation: BAA90555.1.
AK161280 mRNA. Translation: BAE36291.1. Different initiation.
AK165417 mRNA. Translation: BAE38172.1.
AC025794 Genomic DNA. No translation available.
CH466612 Genomic DNA. Translation: EDL33352.1.
BC065173 mRNA. Translation: AAH65173.1.
CCDSCCDS29540.1.
PIRS03600.
RefSeqNP_001154885.1. NM_001161413.1.
NP_032603.3. NM_008577.4.
XP_006526794.1. XM_006526731.1.
XP_006526795.1. XM_006526732.1.
UniGeneMm.4114.

3D structure databases

ProteinModelPortalP10852.
SMRP10852. Positions 105-526.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP10852. 4 interactions.
MINTMINT-4996392.

Protein family/group databases

CAZyGH13. Glycoside Hydrolase Family 13.

PTM databases

PhosphoSiteP10852.

Proteomic databases

MaxQBP10852.
PaxDbP10852.
PRIDEP10852.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000010239; ENSMUSP00000010239; ENSMUSG00000010095. [P10852-1]
ENSMUST00000170157; ENSMUSP00000130194; ENSMUSG00000010095. [P10852-2]
GeneID17254.
KEGGmmu:17254.
UCSCuc012bib.1. mouse. [P10852-1]

Organism-specific databases

CTD6520.
MGIMGI:96955. Slc3a2.

Phylogenomic databases

eggNOGCOG0366.
GeneTreeENSGT00530000063127.
HOVERGENHBG000023.
InParanoidP10852.
KOK06519.
OMANMTVKGQ.
OrthoDBEOG7ZSHSV.
PhylomeDBP10852.
TreeFamTF314498.

Gene expression databases

ArrayExpressP10852.
BgeeP10852.
GenevestigatorP10852.

Family and domain databases

Gene3D2.60.40.1180. 1 hit.
3.20.20.80. 1 hit.
InterProIPR015902. 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]
PANTHERPTHR10357. PTHR10357. 1 hit.
PfamPF00128. Alpha-amylase. 1 hit.
[Graphical view]
SUPFAMSSF51445. SSF51445. 1 hit.
ProtoNetSearch...

Other

NextBio291726.
PROP10852.
SOURCESearch...

Entry information

Entry name4F2_MOUSE
AccessionPrimary (citable) accession number: P10852
Secondary accession number(s): G3UWA6, Q54AH5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot