Transferrin receptor 2 explained

Transferrin receptor 2 (TfR2) is a protein that in humans is encoded by the TFR2 gene.^{[1] [2]} This protein is involved in the uptake of transferrin-bound iron into cells by endocytosis, although its role is minor compared to transferrin receptor 1.

Function

This gene is a member of the transferrin receptor-like family and encodes a single-pass type II membrane protein with a protease associated (PA) domain, an M28 peptidase domain and a transferrin receptor-like dimerization domain. This protein mediates cellular uptake of transferrin-bound iron and mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.^[3]

See also

• Transferrin receptor 1
• Transferrin

Further reading

• Subramaniam VN, Summerville L, Wallace DF . Molecular and cellular characterization of transferrin receptor 2 . Cell Biochem. Biophys. . 36 . 2–3 . 235–9 . 2003 . 12139409 . 10.1385/CBB:36:2-3:235 . 278321 .
• Trinder D, Baker E . Transferrin receptor 2: a new molecule in iron metabolism . Int. J. Biochem. Cell Biol. . 35 . 3 . 292–6 . 2003 . 12531241 . 10.1016/S1357-2725(02)00258-3 .
• Franchini M . Hereditary iron overload: update on pathophysiology, diagnosis, and treatment . Am. J. Hematol. . 81 . 3 . 202–9 . 2006 . 16493621 . 10.1002/ajh.20493 . 40950367 . free .
• Deicher R, Hörl WH . New insights into the regulation of iron homeostasis . Eur. J. Clin. Invest. . 36 . 5 . 301–9 . 2006 . 16634833 . 10.1111/j.1365-2362.2006.01633.x . 1726652 . free .
• Feder JN, Penny DM, Irrinki A, etal . The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding . Proc. Natl. Acad. Sci. U.S.A. . 95 . 4 . 1472–7 . 1998 . 9465039 . 10.1073/pnas.95.4.1472 . 19050 . 1998PNAS...95.1472F . free .
• Kawabata H, Yang R, Hirama T, etal . Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family . J. Biol. Chem. . 274 . 30 . 20826–32 . 1999 . 10409623 . 10.1074/jbc.274.30.20826 . free .
• Bennett MJ, Lebrón JA, Bjorkman PJ . Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor . Nature . 403 . 6765 . 46–53 . 2000 . 10638746 . 10.1038/47417 . 4427272 .
• Kawabata H, Germain RS, Vuong PT, etal . Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo . J. Biol. Chem. . 275 . 22 . 16618–25 . 2000 . 10748106 . 10.1074/jbc.M908846199 . free .
• Camaschella C, Roetto A, Calì A, etal . The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22 . Nat. Genet. . 25 . 1 . 14–5 . 2000 . 10802645 . 10.1038/75534 . 9227077 .
• West AP, Bennett MJ, Sellers VM, etal . Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE . J. Biol. Chem. . 275 . 49 . 38135–8 . 2001 . 11027676 . 10.1074/jbc.C000664200 . 14295069 . free .
• Roetto A, Totaro A, Piperno A, etal . New mutations inactivating transferrin receptor 2 in hemochromatosis type 3 . Blood . 97 . 9 . 2555–60 . 2001 . 11313241 . 10.1182/blood.V97.9.2555 . 36015072 . free .
• Kawabata H, Nakamaki T, Ikonomi P, etal . Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells . Blood . 98 . 9 . 2714–9 . 2001 . 11675342 . 10.1182/blood.V98.9.2714 . free .
• Fleming RE, Ahmann JR, Migas MC, etal . Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis . Proc. Natl. Acad. Sci. U.S.A. . 99 . 16 . 10653–8 . 2002 . 12134060 . 10.1073/pnas.162360699 . 125003 . free .
• Hofmann WK, Tong XJ, Ajioka RS, etal . Mutation analysis of transferrin-receptor 2 in patients with atypical hemochromatosis . Blood . 100 . 3 . 1099–100 . 2002 . 12150153 . 10.1182/blood-2002-04-1077 . free .
• Deaglio S, Capobianco A, Calì A, etal . Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum . Blood . 100 . 10 . 3782–9 . 2003 . 12393650 . 10.1182/blood-2002-01-0076 . free .
• Vogt TM, Blackwell AD, Giannetti AM, etal . Heterotypic interactions between transferrin receptor and transferrin receptor 2 . Blood . 101 . 5 . 2008–14 . 2003 . 12406888 . 10.1182/blood-2002-09-2742 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .

External links

• GeneReviews/NIH/NCBI/UW entry on TFR2-Related or Type 3 Hereditary Hemochromatosis

Notes and References

1. Glockner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A . Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes . Genome Res . 8 . 10 . 1060–73 . Dec 1998 . 9799793 . 310788 . 10.1101/gr.8.10.1060.
2. Mattman A, Huntsman D, Lockitch G, Langlois S, Buskard N, Ralston D, Butterfield Y, Rodrigues P, Jones S, Porto G, Marra M, De Sousa M, Vatcher G . Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation . Blood . 100 . 3 . 1075–7 . Jul 2002 . 12130528 . 10.1182/blood-2002-01-0133 . 10400.16/826 . free . free .
3. Web site: Entrez Gene: TFR2 transferrin receptor 2.