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

Names and origin

Protein names

Recommended name:
    4F2 cell-surface antigen heavy chain
      Short name=4F2hc
Alternative name(s):
    CD_antigen=CD98

Gene names

Name:	Slc3a2
Synonyms:	Mdu1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	526 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.6 Ref.7 Ref.9
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.
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.
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.6 Ref.1 Ref.8
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.6
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.6 Ref.1
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.

Ontologies

Keywords
Biological process	Amino-acid transport Transport
Cellular component	Cell membrane Membrane
Domain	Signal-anchor Transmembrane
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro leucine import Inferred from sequence or structural similarity. Source: UniProtKB tryptophan transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro cation binding Inferred from electronic annotation. Source: InterPro neutral amino acid transmembrane transporter activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 526	526	4F2 cell-surface antigen heavy chain		PRO_0000064384
Regions
	Topological domain	1 – 75	75	Cytoplasmic Potential
	Transmembrane	76 – 99	24	Signal-anchor for type II membrane protein
	Topological domain	100 – 526	427	Extracellular Potential
Amino acid modifications
	Modified residue	2	1	Phosphoserine By similarity
	Modified residue	5	1	Phosphothreonine By similarity
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	259	1	N-linked (GlcNAc...) Potential
	Glycosylation	263	1	N-linked (GlcNAc...) Potential
	Glycosylation	301	1	N-linked (GlcNAc...) Potential
	Glycosylation	318	1	N-linked (GlcNAc...) Potential
	Glycosylation	385	1	N-linked (GlcNAc...) Potential
	Glycosylation	399	1	N-linked (GlcNAc...) Potential
	Glycosylation	509	1	N-linked (GlcNAc...) Potential
	Disulfide bond	103		Interchain (with light chain) Probable
	Cross-link	42		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Experimental info
	Mutagenesis	103	1	C → S: No effect on guidance of LAT1 to the plasma membrane. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P10852-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: AE6261F11C7D9468	FASTA	526	58,337
	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

References

	« Hide 'large scale' referencesShow '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: 2928113] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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]. 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. , 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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Kidney and Testis.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[5]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 43-53; 163-171; 456-463 AND 488-496, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[6]	"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: 9915839] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, MUTAGENESIS OF CYS-103. Strain: BALB/c.
[7]	"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: 10391915] [Abstract] Cited for: FUNCTION, SUBUNIT.
[8]	"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: 10574970] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"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: 11011012] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X14309 mRNA. Translation: CAA32490.1. AB023408 mRNA. Translation: BAA90555.1. AK161280 mRNA. Translation: BAE36291.1. AK165417 mRNA. Translation: BAE38172.1. BC065173 mRNA. Translation: AAH65173.1.
IPI	IPI00114641.
PIR	S03600.
UniGene	Mm.4114
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GH13. Glycoside Hydrolase Family 13.
PTM databases
PhosphoSite	P10852.
Proteomic databases
PRIDE	P10852.
Genome annotation databases
Ensembl	ENSMUSG00000010095. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:96955. Slc3a2.
Phylogenomic databases
HOVERGEN	P10852.
OMA	P10852. NMTVKGQ.
Gene expression databases
ArrayExpress	P10852.
Bgee	P10852.
GermOnline	ENSMUSG00000010095. Mus musculus.
Family and domain databases
InterPro	IPR006047. Glyco_hydro_13_cat. IPR013781. Glyco_hydro_sg_catalytic. [Graphical view]
Gene3D	G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit.
Pfam	PF00128. Alpha-amylase. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

4F2_MOUSE

Accession

Primary (citable) accession number: P10852
Secondary accession number(s): Q54AH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	July 7, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)