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P08195

- 4F2_HUMAN

UniProt

P08195 - 4F2_HUMAN

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Protein

4F2 cell-surface antigen heavy chain

Gene

SLC3A2

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. calcium:sodium antiporter activity Source: UniProtKB
  2. catalytic activity Source: InterPro
  3. cation binding Source: InterPro
  4. double-stranded RNA binding Source: MGI
  5. neutral amino acid transmembrane transporter activity Source: UniProtKB
  6. poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  1. amino acid transport Source: UniProtKB
  2. blood coagulation Source: Reactome
  3. calcium ion transport Source: UniProtKB
  4. carbohydrate metabolic process Source: InterPro
  5. cell growth Source: UniProtKB
  6. ion transport Source: Reactome
  7. leucine import Source: UniProtKB
  8. leukocyte migration Source: Reactome
  9. response to exogenous dsRNA Source: MGI
  10. sodium ion transmembrane transport Source: GOC
  11. transmembrane transport Source: Reactome
  12. 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: 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

  1. cell junction Source: HPA
  2. cell surface Source: UniProtKB
  3. cytoplasm Source: HPA
  4. extracellular vesicular exosome Source: UniProtKB
  5. integral component of membrane Source: UniProtKB
  6. membrane Source: UniProtKB
  7. nucleus Source: HPA
  8. 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 6306304F2 cell-surface antigen heavy chainPRO_0000064383Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine2 Publications
Modified residuei103 – 1031Phosphoserine1 Publication
Modified residuei134 – 1341Phosphoserine1 Publication
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

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.3 Publications

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.
GenevestigatoriP08195.

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. 31 interactions.
IntActiP08195. 11 interactions.
MINTiMINT-4999018.
STRINGi9606.ENSP00000367124.

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.
OMAiNMTVKGQ.
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.

This entry describes 4 isoformsi produced by alternative splicing. Align

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. [P08195-1]
GeneIDi6520.
KEGGihsa:6520.
UCSCiuc001nwd.3. human. [P08195-1]
uc001nwf.3. human. [P08195-3]

Polymorphism databases

DMDMi257051063.

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.
CCDSi CCDS31589.1. [P08195-3 ]
CCDS31590.1. [P08195-2 ]
CCDS8039.2. [P08195-1 ]
PIRi A28455. SAHU4F.
RefSeqi NP_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 ]
UniGenei Hs.502769.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2DH2 X-ray 2.10 A 212-630 [» ]
2DH3 X-ray 2.80 A/B 212-630 [» ]
ProteinModelPortali P08195.
SMRi P08195. Positions 212-630.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112411. 31 interactions.
IntActi P08195. 11 interactions.
MINTi MINT-4999018.
STRINGi 9606.ENSP00000367124.

Protein family/group databases

CAZyi GH13. Glycoside Hydrolase Family 13.
TCDBi 8.A.9.2.2. the rbat transport accessory protein (rbat) family.

PTM databases

PhosphoSitei P08195.

Polymorphism databases

DMDMi 257051063.

Proteomic databases

MaxQBi P08195.
PaxDbi P08195.
PRIDEi P08195.

Protocols and materials databases

DNASUi 6520.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000338663 ; ENSP00000340815 ; ENSG00000168003 . [P08195-2 ]
ENST00000377889 ; ENSP00000367121 ; ENSG00000168003 . [P08195-3 ]
ENST00000377890 ; ENSP00000367122 ; ENSG00000168003 . [P08195-1 ]
GeneIDi 6520.
KEGGi hsa:6520.
UCSCi uc001nwd.3. human. [P08195-1 ]
uc001nwf.3. human. [P08195-3 ]

Organism-specific databases

CTDi 6520.
GeneCardsi GC11P062623.
HGNCi HGNC:11026. SLC3A2.
HPAi CAB010455.
HPA017980.
MIMi 158070. gene.
neXtProti NX_P08195.
PharmGKBi PA35894.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0366.
GeneTreei ENSGT00530000063127.
HOGENOMi HOG000233529.
HOVERGENi HBG000023.
InParanoidi P08195.
KOi K06519.
OMAi NMTVKGQ.
OrthoDBi EOG7ZSHSV.
PhylomeDBi P08195.

Enzyme and pathway databases

BioCyci MetaCyc:ENSG00000168003-MONOMER.
Reactomei REACT_12560. Basigin interactions.
REACT_13796. Amino acid transport across the plasma membrane.
SABIO-RK P08195.

Miscellaneous databases

ChiTaRSi SLC3A2. human.
EvolutionaryTracei P08195.
GeneWikii SLC3A2.
GenomeRNAii 6520.
NextBioi 25353.
PROi P08195.
SOURCEi Search...

Gene expression databases

Bgeei P08195.
CleanExi HS_SLC3A2.
ExpressionAtlasi P08195. baseline and differential.
Genevestigatori P08195.

Family and domain databases

Gene3Di 2.60.40.1180. 1 hit.
3.20.20.80. 1 hit.
InterProi 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 ]
PANTHERi PTHR10357. PTHR10357. 1 hit.
Pfami PF00128. Alpha-amylase. 2 hits.
[Graphical view ]
SUPFAMi SSF51445. SSF51445. 1 hit.
ProtoNeti Search...

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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-134, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  43. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  44. "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: November 26, 2014
This is version 172 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