4F2 cell-surface antigen heavy chain (SLC3A2)
The protein contains 630 amino acids for an estimated molecular weight of 67994 Da.
Component of several heterodimeric complexes involved in amino acid transport (PubMed:11557028, PubMed:9829974, PubMed:9751058, PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:30341327). The precise substrate specificity depends on the other subunit in the heterodimer (PubMed:9829974, PubMed:9751058, PubMed:10391915, PubMed:10574970, PubMed:30867591, PubMed:10903140). The complexes function as amino acid exchangers (PubMed:11557028, PubMed:10903140, PubMed:12117417, PubMed:12225859, PubMed:30867591). The homodimer functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine, methionine and tryptophan (PubMed:9751058, PubMed:11557028, PubMed:11311135, PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:25998567, PubMed:30867591). The heterodimer formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7 mediates the uptake of dibasic amino acids (PubMed:9829974, PubMed:10903140). The heterodimer with SLC7A5/LAT1 mediates the transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694, PubMed:12225859). The heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). The heterodimer with SLC7A5/LAT1 is involved in the uptake of leucine (PubMed:25998567, PubMed:30341327). When associated with LAPTM4B, the h (updated: June 2, 2021)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Amino acid transport
Calcium ion transport
Carbohydrate metabolic process
L-alanine import across plasma membrane
L-alpha-amino acid transmembrane transport
L-leucine import across plasma membrane
Leucine import across plasma membrane
Leukocyte migration
Phenylalanine transport
Response to exogenous dsRNA
Tryptophan transport
Cellular Component
Amino acid transport complex
Apical plasma membrane
Basal plasma membrane
Basolateral plasma membrane
Cell junction
Cell surface
Cytosol
Extracellular exosome
Integral component of membrane
Lysosomal membrane
Melanosome
Membrane
Nucleoplasm
Nucleus
Plasma membrane
Molecular Function
Aromatic amino acid transmembrane transporter activity
Cadherin binding
Calcium:sodium antiporter activity
Catalytic activity
Double-stranded RNA binding
L-alanine transmembrane transporter activity
L-leucine transmembrane transporter activity
Neutral amino acid transmembrane transporter activity
RNA binding
The reference OMIM entry for this protein is 158070
Solute carrier family 3 (activator of dibasic and neutral amino acid transport), member 2; slc3a2
Mdu1
Antigen defined by monoclonal antibody 4f2, heavy chain
4f2 heavy chain; 4f2hc
Cd98 heavy chain; cd98; cd98hc monoclonal antibody 44d7, inc
CLONING
Haynes et al. (1981) defined a monoclonal antibody variously called 4F2 and MDU1. (MDU1 is derived from 'monoclonal, Duke University.') Lumadue et al. (1987) presented the cDNA-derived amino acid sequence of lymphocyte activation antigen 4F2. Their data indicate that the molecule is 529 amino acids long with an internal signal sequence and a single transmembrane domain. Because of the expression of the molecule on actively proliferating cells of various origins, including embryonic skin and lung, basal-layer keratinocytes, fibrosarcomas, osteosarcomas, and rhabdomyosarcomas, the 4F2 molecule may play a role in cell division. Hemler and Strominger (1982) showed that 4F2 recognizes a determinant on the 65-kD polypeptide backbone of the heavy chain of an approximately 120-kD cell surface glycoprotein that also has a 40-kD unglycosylated light chain (SLC7A5; 600182). Quackenbush et al. (1987) isolated a cDNA for the heavy chain. The sequence suggests that the heavy chain cDNA encodes a type II membrane glycoprotein. The cDNAs are derived from a single-copy gene that has been highly conserved during mammalian evolution. Regulation of expression of the heavy chain gene was studied by Lindsten et al. (1988).GENE FUNCTION
Posillico et al. (1985) demonstrated that the cell surface protein identified by 4F2 modulates intracellular calcium. It is a heteromeric glycoprotein with unique tissue distribution including activated T cells, neuroendocrine cells, and all malignant cell lines. Michalak et al. (1986) showed that both the 44D7 and the 4F2 monoclonal antibodies inhibit specifically the sodium-dependent calcium fluxes characteristic of Na+/Ca(2+) exchanges of cardiac and skeletal muscle. Quackenbush et al. (1987) reviewed the evidence pointing to a role of the 4F2 molecule in the regulation of intracellular calcium concentration and the concomitant control of growth, excitability, and endocrine secretion. Amino acid transport across cellular plasma membranes depends on several parallel-functioning transporters and exchangers. The widespread transport system L accounts for a sodium-independent exchange of large neutral amino acids, whereas the system y(+)L exchanges positively charged amino acids and/or neutral amino acids together with sodium. The 4F2 heavy chain alone facilitates amino acid transport through both the L-type and the y(+)L-type systems, depending on the cellular system. Mastroberardino et al. (1998) identified the permease-related protein E16 (600182) as the first light chain of the 4F2 heavy chain and showed that the resulting heterodimeric complex mediates L-type amino acid transport. They hypothesized that at least one other related light chain may associate with the 4F2 heavy chain to produce a heterodimeric transporter with y(+)L transport characteristics. The MDU1 gene is associated with endocrine cell function including that of pancreatic islet cells, thyroid C cells, and parathyroid cells (Posillico et al., 1987). Antibodies to the MDU1 cell surface glycoprotein modulate intracellular calcium and can stimulate parathyroid hormone secretion. Sato et al. (1999) determined that uptake of cystine in Xenopus oocytes increased substantially when mouse xCT (607933) cRNA was coinjected with 4f2hc cRNA. Injection of either cRNA alone did not enhance uptake of cystine and glutamate.GENE STRUCTURE
Gottesdiener et al. (1988) showed that the gene for the heavy chain of 4F2 spans 8 kb and is ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 158070 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).