P08195 (4F2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
4F2 cell-surface antigen heavy chain
Short name=4F2hc

Alternative name(s):
4F2 heavy chain antigen
Lymphocyte activation antigen 4F2 large subunit
CD_antigen=CD98

Gene names

Name:	SLC3A2
Synonyms:	MDU1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	630 AA.
Sequence status	Complete.
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.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.22 Ref.23 Ref.25 Ref.26 Ref.28 Ref.29
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. 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. Ref.6 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.25 Ref.26 Ref.29 Ref.41
Subcellular location	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. Ref.16 Ref.17 Ref.20 Ref.23 Ref.26 Ref.32 Ref.33 Ref.41
Tissue specificity	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. Ref.4 Ref.5 Ref.6 Ref.17 Ref.20 Ref.25 Ref.26 Ref.28 Ref.32
Induction	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. Ref.4 Ref.5 Ref.20
Post-translational modification	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.
Miscellaneous	Arginine uptake is inhibited by increasing concentrations of leucine in the presence of Na+.
Sequence similarities	Belongs to the SLC3A transporter family.
Biophysicochemical properties	Kinetic parameters: KM=295 µM for glutamine (in the presence of NaCl) Ref.15 KM=236 µM for leucine (in the presence of NaCl) KM=120 µM for arginine (in the presence of NaCl) KM=138 µM for arginine (in the absence of NaCl)
Mass spectrometry	Molecular mass is 57944.93 Da from positions 1 - 529. Determined by MALDI. Ref.24

Ontologies

Keywords
Biological process	Amino-acid transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Acetylation Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro cell growth Non-traceable author statement Ref.1. Source: UniProtKB leucine import Inferred from sequence or structural similarity. Source: UniProtKB leukocyte migration Traceable author statement. Source: Reactome tryptophan transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome
Molecular_function	calcium:sodium antiporter activity Traceable author statement PubMed 10673541. Source: UniProtKB 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
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P08195-1)

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: P08195-2)

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

Isoform 3 (identifier: P08195-3)

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

Isoform 4 (identifier: P08195-4)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 630

630

4F2 cell-surface antigen heavy chain

PRO_0000064383

Regions

Topological domain

102 – 184

83

Cytoplasmic Potential

Transmembrane

185 – 205

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

206 – 630

425

Extracellular Potential

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.9

Modified residue

103

1

Phosphoserine Ref.40

Modified residue

134

1

Phosphoserine Ref.40

Modified residue

165

1

Phosphoserine Ref.38

Modified residue

406

1

Phosphoserine Probable

Modified residue

408

1

Phosphoserine Probable

Modified residue

410

1

Phosphoserine Probable

Modified residue

527

1

Phosphoserine Probable

Modified residue

531

1

Phosphoserine Probable

Glycosylation

365

1

N-linked (GlcNAc...) Ref.27 Ref.36 Ref.37

Glycosylation

381

1

N-linked (GlcNAc...) Ref.27 Ref.30 Ref.36 Ref.37

Glycosylation

424

1

N-linked (GlcNAc...) Ref.27 Ref.30 Ref.37

Glycosylation

506

1

N-linked (GlcNAc...) Ref.36 Ref.37

Disulfide bond

210

Interchain (with light chain) Ref.41

Cross-link

147

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.34

Natural variations

Alternative sequence

1 – 101

101

Missing in isoform 2.

VSP_037907

Alternative sequence

38 – 99

62

Missing in isoform 3.

VSP_037908

Alternative sequence

98

1

V → VTETGFHHVSQADIEFLTSI DPTASASGSAGI in isoform 4.

VSP_037909

Experimental info

Mutagenesis

210

1

C → S: Abolishes dimerization, leucine uptake and interaction with beta-1 integrins. Ref.12 Ref.18 Ref.41

Mutagenesis

431

1

C → S: No effect on dimerization, leucine uptake or interaction with beta-1 integrins. Ref.12 Ref.18

Sequence conflict

137

1

G → E in AAA35536. Ref.4

Sequence conflict

158

1

A → P in AAA51540. Ref.3

Sequence conflict

223

1

A → P in AAA35536. Ref.4

Sequence conflict

315

1

E → D in AAA35536. Ref.4

Sequence conflict

320

1

S → F in AAA35489. Ref.5

Sequence conflict

372

1

E → G in AAA35536. Ref.4

Sequence conflict

412 – 413

2

GE → PQ in AAA35536. Ref.4

Sequence conflict

465

1

V → L in AAA35536. Ref.4

Sequence conflict

481

1

G → P in AAA35536. Ref.4

Sequence conflict

549

1

G → E in AAA35489. Ref.5

Sequence conflict

609

1

L → P in AAA35536. Ref.4

Sequence conflict

612

1

E → G in AAA35536. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

630

Helix Strand Turn

Details...

Helix

218 – 220

3

Beta strand

224 – 227

4

Helix

230 – 234

5

Helix

241 – 245

5

Helix

248 – 253

6

Beta strand

257 – 261

5

Beta strand

265 – 267

3

Beta strand

275 – 280

6

Helix

282 – 284

3

Helix

287 – 299

13

Beta strand

303 – 307

5

Turn

310 – 313

4

Beta strand

314 – 316

3

Beta strand

319 – 321

3

Helix

323 – 340

18

Beta strand

344 – 347

4

Helix

350 – 352

3

Helix

356 – 370

15

Beta strand

375 – 379

5

Helix

385 – 391

7

Turn

392 – 394

3

Beta strand

399 – 401

3

Turn

404 – 407

4

Helix

412 – 426

15

Beta strand

437 – 439

3

Helix

441 – 443

3

Helix

447 – 449

3

Helix

450 – 457

8

Beta strand

460 – 467

8

Helix

470 – 472

3

Helix

476 – 478

3

Beta strand

479 – 481

3

Beta strand

484 – 486

3

Helix

493 – 495

3

Helix

500 – 502

3

Helix

505 – 507

3

Helix

509 – 513

5

Helix

519 – 532

14

Helix

534 – 538

5

Beta strand

540 – 545

6

Beta strand

550 – 556

7

Beta strand

562 – 568

7

Beta strand

570 – 572

3

Beta strand

581 – 583

3

Helix

585 – 587

3

Beta strand

591 – 603

13

Beta strand

607 – 610

4

Helix

611 – 613

3

Beta strand

621 – 626

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 1, 2009. Version 3. Checksum: AE427F8204CC10B0	FASTA	630	67,994
	10 20 30 40 50 60 MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS 70 80 90 100 110 120 ASQNAEMIET GSDCVTQAGL QLLASSDPPA LASKNAEVTG TMSQDTEVDM KEVELNELEP 130 140 150 160 170 180 EKQPMNAASG AAMSLAGAEK NGLVKIKVAE DEAEAAAAAK FTGLSKEELL KVAGSPGWVR 190 200 210 220 230 240 TRWALLLLFW LGWLGMLAGA VVIIVRAPRC RELPAQKWWH TGALYRIGDL QAFQGHGAGN 250 260 270 280 290 300 LAGLKGRLDY LSSLKVKGLV LGPIHKNQKD DVAQTDLLQI DPNFGSKEDF DSLLQSAKKK 310 320 330 340 350 360 SIRVILDLTP NYRGENSWFS TQVDTVATKV KDALEFWLQA GVDGFQVRDI ENLKDASSFL 370 380 390 400 410 420 AEWQNITKGF SEDRLLIAGT NSSDLQQILS LLESNKDLLL TSSYLSDSGS TGEHTKSLVT 430 440 450 460 470 480 QYLNATGNRW CSWSLSQARL LTSFLPAQLL RLYQLMLFTL PGTPVFSYGD EIGLDAAALP 490 500 510 520 530 540 GQPMEAPVML WDESSFPDIP GAVSANMTVK GQSEDPGSLL SLFRRLSDQR SKERSLLHGD 550 560 570 580 590 600 FHAFSAGPGL FSYIRHWDQN ERFLVVLNFG DVGLSAGLQA SDLPASASLP AKADLLLSTQ 610 620 630 PGREEGSPLE LERLKLEPHE GLLLRFPYAA
	Isoform 2 [UniParc]. Checksum: 82F26856737E8F31	FASTA	529	57,945
	10 20 30 40 50 60 MSQDTEVDMK EVELNELEPE KQPMNAASGA AMSLAGAEKN GLVKIKVAED EAEAAAAAKF 70 80 90 100 110 120 TGLSKEELLK VAGSPGWVRT RWALLLLFWL GWLGMLAGAV VIIVRAPRCR ELPAQKWWHT 130 140 150 160 170 180 GALYRIGDLQ AFQGHGAGNL AGLKGRLDYL SSLKVKGLVL GPIHKNQKDD VAQTDLLQID 190 200 210 220 230 240 PNFGSKEDFD SLLQSAKKKS IRVILDLTPN YRGENSWFST QVDTVATKVK DALEFWLQAG 250 260 270 280 290 300 VDGFQVRDIE NLKDASSFLA EWQNITKGFS EDRLLIAGTN SSDLQQILSL LESNKDLLLT 310 320 330 340 350 360 SSYLSDSGST GEHTKSLVTQ YLNATGNRWC SWSLSQARLL TSFLPAQLLR LYQLMLFTLP 370 380 390 400 410 420 GTPVFSYGDE IGLDAAALPG QPMEAPVMLW DESSFPDIPG AVSANMTVKG QSEDPGSLLS 430 440 450 460 470 480 LFRRLSDQRS KERSLLHGDF HAFSAGPGLF SYIRHWDQNE RFLVVLNFGD VGLSAGLQAS 490 500 510 520 DLPASASLPA KADLLLSTQP GREEGSPLEL ERLKLEPHEG LLLRFPYAA
	Isoform 3 [UniParc]. Checksum: F2B9400F95F2E1BD	FASTA	568	61,816
	10 20 30 40 50 60 MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSGTM SQDTEVDMKE VELNELEPEK 70 80 90 100 110 120 QPMNAASGAA MSLAGAEKNG LVKIKVAEDE AEAAAAAKFT GLSKEELLKV AGSPGWVRTR 130 140 150 160 170 180 WALLLLFWLG WLGMLAGAVV IIVRAPRCRE LPAQKWWHTG ALYRIGDLQA FQGHGAGNLA 190 200 210 220 230 240 GLKGRLDYLS SLKVKGLVLG PIHKNQKDDV AQTDLLQIDP NFGSKEDFDS LLQSAKKKSI 250 260 270 280 290 300 RVILDLTPNY RGENSWFSTQ VDTVATKVKD ALEFWLQAGV DGFQVRDIEN LKDASSFLAE 310 320 330 340 350 360 WQNITKGFSE DRLLIAGTNS SDLQQILSLL ESNKDLLLTS SYLSDSGSTG EHTKSLVTQY 370 380 390 400 410 420 LNATGNRWCS WSLSQARLLT SFLPAQLLRL YQLMLFTLPG TPVFSYGDEI GLDAAALPGQ 430 440 450 460 470 480 PMEAPVMLWD ESSFPDIPGA VSANMTVKGQ SEDPGSLLSL FRRLSDQRSK ERSLLHGDFH 490 500 510 520 530 540 AFSAGPGLFS YIRHWDQNER FLVVLNFGDV GLSAGLQASD LPASASLPAK ADLLLSTQPG 550 560 REEGSPLELE RLKLEPHEGL LLRFPYAA
	Isoform 4 [UniParc]. Checksum: 06C2CDFD6B1D93F5	FASTA	661	71,123
	10 20 30 40 50 60 MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS 70 80 90 100 110 120 ASQNAEMIET GSDCVTQAGL QLLASSDPPA LASKNAEVTE TGFHHVSQAD IEFLTSIDPT 130 140 150 160 170 180 ASASGSAGIT GTMSQDTEVD MKEVELNELE PEKQPMNAAS GAAMSLAGAE KNGLVKIKVA 190 200 210 220 230 240 EDEAEAAAAA KFTGLSKEEL LKVAGSPGWV RTRWALLLLF WLGWLGMLAG AVVIIVRAPR 250 260 270 280 290 300 CRELPAQKWW HTGALYRIGD LQAFQGHGAG NLAGLKGRLD YLSSLKVKGL VLGPIHKNQK 310 320 330 340 350 360 DDVAQTDLLQ IDPNFGSKED FDSLLQSAKK KSIRVILDLT PNYRGENSWF STQVDTVATK 370 380 390 400 410 420 VKDALEFWLQ AGVDGFQVRD IENLKDASSF LAEWQNITKG FSEDRLLIAG TNSSDLQQIL 430 440 450 460 470 480 SLLESNKDLL LTSSYLSDSG STGEHTKSLV TQYLNATGNR WCSWSLSQAR LLTSFLPAQL 490 500 510 520 530 540 LRLYQLMLFT LPGTPVFSYG DEIGLDAAAL PGQPMEAPVM LWDESSFPDI PGAVSANMTV 550 560 570 580 590 600 KGQSEDPGSL LSLFRRLSDQ RSKERSLLHG DFHAFSAGPG LFSYIRHWDQ NERFLVVLNF 610 620 630 640 650 660 GDVGLSAGLQ ASDLPASASL PAKADLLLST QPGREEGSPL ELERLKLEPH EGLLLRFPYA A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines." Yanagida O., Kanai Y., Chairoungdua A., Kim D.K., Segawa H., Nii T., Cha S.H., Matsuo H., Fukushima J., Fukasawa Y., Tani Y., Taketani Y., Uchino H., Kim J.Y., Inatomi J., Okayasu I., Miyamoto K., Takeda E., Goya T., Endou H. Biochim. Biophys. Acta 1514:291-302(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, TISSUE SPECIFICITY. Tissue: Placenta.
[7]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] 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, 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, 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, MASS SPECTROMETRY. 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]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[34]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-147, MASS SPECTROMETRY.
[35]	"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.
[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, MASS SPECTROMETRY. Tissue: Liver.
[37]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[38]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[39]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[40]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-134, MASS SPECTROMETRY.
[41]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00027493.
IPI00554481.
IPI00554722.
IPI00604710.

PIR

SAHU4F. A28455.

RefSeq

NP_001012680.1. NM_001012662.2.
NP_001012682.1. NM_001012664.2.
NP_001013269.1. NM_001013251.2.
NP_002385.3. NM_002394.5.

UniGene

Hs.502769.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DH2	X-ray	2.10	A	212-630	[»]
2DH3	X-ray	2.80	A/B	212-630	[»]

ProteinModelPortal

P08195.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08195. 8 interactions.

STRING

9606.ENSP00000367124.

Protein family/group databases

CAZy

GH13. Glycoside Hydrolase Family 13.

TCDB

8.A.9.2.2. rBAT transport accessory protein (rBAT) family.

PTM databases

PhosphoSite

P08195.

Polymorphism databases

DMDM

257051063.

Proteomic databases

PaxDb

P08195.

PRIDE

P08195.

Protocols and materials databases

DNASU

6520.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338663; ENSP00000340815; ENSG00000168003.
ENST00000377889; ENSP00000367121; ENSG00000168003.
ENST00000377890; ENSP00000367122; ENSG00000168003.
ENST00000377892; ENSP00000367124; ENSG00000168003.

GeneID

6520.

KEGG

hsa:6520.

UCSC

uc001nwc.3. human.
uc001nwd.3. human.
uc001nwf.3. human.

Organism-specific databases

CTD

6520.

GeneCards

GC11P062623.

HGNC

HGNC:11026. SLC3A2.

HPA

CAB010455.
HPA017980.

MIM

158070. gene.

neXtProt

NX_P08195.

PharmGKB

PA35894.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0366.

HOGENOM

HOG000233529.

HOVERGEN

HBG000023.

InParanoid

P08195.

KO

K06519.

OMA

NMTVKGQ.

OrthoDB

EOG4S7JPP.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000168003-MONOMER.

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.

Reactome

REACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P08195.

Bgee

P08195.

CleanEx

HS_SLC3A2.

Genevestigator

P08195.

Family and domain databases

Gene3D

2.60.40.1180. 1 hit.
3.20.20.80. 1 hit.

InterPro

IPR015902. 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]

PANTHER

PTHR10357. PTHR10357. 1 hit.

Pfam

PF00128. Alpha-amylase. 1 hit.
[Graphical view]

SUPFAM

SSF51445. Glyco_hydro_cat. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

SLC3A2. human.

EvolutionaryTrace

P08195.

GenomeRNAi

6520.

NextBio

25353.

SOURCE

Search...

Entry information

Entry name

4F2_HUMAN

Accession

Primary (citable) accession number: P08195
Secondary accession number(s): Q13543

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	September 1, 2009
Last modified:	May 1, 2013
This is version 154 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.