Melanotransferrin Explained

Melanotransferrin is a protein that in humans is encoded by the MFI2 gene. MFI2 has also recently been designated CD228 (cluster of differentiation 228).

The protein encoded by this gene is a cell-surface glycoprotein found on melanoma cells. The protein shares sequence similarity and iron-binding properties with members of the transferrin superfamily. The importance of the iron binding function has not yet been identified. This gene resides in the same region of chromosome 3 as members of the transferrin superfamily. Alternative splicing results in two transcript variants.^[1] It is part of neural crest tissue, often present in melanotic neuroectodermal tumor of infancy.

Further reading

• Suryo Rahmanto Y, Dunn LL, Richardson DR . The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark--from iron metabolism to tumorigenesis. . Oncogene . 26 . 42 . 6113–24 . 2007 . 17452986 . 10.1038/sj.onc.1210442 . 35884470 .
• Baker EN, Baker HM, Smith CA, etal . Human melanotransferrin (p97) has only one functional iron-binding site. . FEBS Lett. . 298 . 2–3 . 215–8 . 1992 . 1544447 . 10.1016/0014-5793(92)80060-T . 21022972 . 1992FEBSL.298..215B .
• Garratt RC, Jhotí H . A molecular model for the tumour-associated antigen, p97, suggests a Zn-binding function. . FEBS Lett. . 305 . 1 . 55–61 . 1992 . 1633859 . 10.1016/0014-5793(92)80654-Y . 23569786 . free . 1992FEBSL.305...55G .
• Rose TM, Plowman GD, Teplow DB, etal . Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 5 . 1261–5 . 1986 . 2419904 . 10.1073/pnas.83.5.1261 . 323055 . 1986PNAS...83.1261R . free .
• Furukawa KS, Furukawa K, Real FX, etal . A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97. . J. Exp. Med. . 169 . 2 . 585–90 . 1989 . 2463331 . 10.1084/jem.169.2.585 . 2189208 .
• Sciot R, de Vos R, van Eyken P, etal . In situ localization of melanotransferrin (melanoma-associated antigen P97) in human liver. A light- and electronmicroscopic immunohistochemical study. . Liver . 9 . 2 . 110–9 . 1989 . 2540389 . 10.1111/j.1600-0676.1989.tb00387.x.
• Seligman PA, Butler CD, Massey EJ, etal . The p97 antigen is mapped to the q24-qter region of chromosome 3; the same region as the transferrin receptor. . Am. J. Hum. Genet. . 38 . 4 . 540–8 . 1986 . 3010712 . 1684788 .
• Le Beau MM, Diaz MO, Plowman GD, etal . Chromosomal sublocalization of the human p97 melanoma antigen. . Hum. Genet. . 72 . 4 . 294–6 . 1986 . 3754536 . 10.1007/BF00290951 . 38961040 .
• Plowman GD, Brown JP, Enns CA, etal . Assignment of the gene for human melanoma-associated antigen p97 to chromosome 3. . Nature . 303 . 5912 . 70–2 . 1983 . 6843660 . 10.1038/303070a0 . 1983Natur.303...70P . 4332107 .
• Kennard ML, Richardson DR, Gabathuler R, etal . A novel iron uptake mechanism mediated by GPI-anchored human p97. . EMBO J. . 14 . 17 . 4178–86 . 1995 . 7556058 . 10.1002/j.1460-2075.1995.tb00091.x. 394500 .
• Food MR, Rothenberger S, Gabathuler R, etal . Transport and expression in human melanomas of a transferrin-like glycosylphosphatidylinositol-anchored protein. . J. Biol. Chem. . 269 . 4 . 3034–40 . 1994 . 10.1016/S0021-9258(17)42043-6 . 8300636 . free .
• Rothenberger S, Food MR, Gabathuler R, etal . Coincident expression and distribution of melanotransferrin and transferrin receptor in human brain capillary endothelium. . Brain Res. . 712 . 1 . 117–21 . 1996 . 8705293 . 10.1016/0006-8993(96)88505-2 . 45470799 .
• Chi DD, Merchant RE, Rand R, etal . Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas. . Am. J. Pathol. . 150 . 6 . 2143–52 . 1997 . 9176405 . 1858329 .
• Richardson DR . The role of the membrane-bound tumour antigen, melanotransferrin (p97), in iron uptake by the human malignant melanoma cell. . Eur. J. Biochem. . 267 . 5 . 1290–8 . 2000 . 10691965 . 10.1046/j.1432-1327.2000.01079.x .
• Dias Neto E, Correa RG, Verjovski-Almeida S, etal . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3491–6 . 2000 . 10737800 . 10.1073/pnas.97.7.3491 . 16267 . 2000PNAS...97.3491D . free .
• Suzuki Y, Tsunoda T, Sese J, etal . Identification and characterization of the potential promoter regions of 1031 kinds of human genes. . Genome Res. . 11 . 5 . 677–84 . 2001 . 11337467 . 10.1101/gr.gr-1640r. 311086 .
• Sekyere E, Food MR, Richardson DR . A second melanotransferrin gene (MTf2) and a novel protein isoform: explanation for the membrane-bound and soluble forms of melanotransferrin? . FEBS Lett. . 512 . 1–3 . 350–2 . 2002 . 11852110 . 10.1016/S0014-5793(02)02248-2 . 38104056 . 2002FEBSL.512..350S .
• Food MR, Sekyere EO, Richardson DR . The soluble form of the membrane-bound transferrin homologue, melanotransferrin, inefficiently donates iron to cells via nonspecific internalization and degradation of the protein. . Eur. J. Biochem. . 269 . 18 . 4435–45 . 2002 . 12230555 . 10.1046/j.1432-1033.2002.03140.x . 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 .
• Guo J, Wen DR, Huang RR, etal . Detection of multiple melanoma-associated markers in melanoma cell lines by RT in situ PCR. . Exp. Mol. Pathol. . 74 . 2 . 140–7 . 2003 . 12710945 . 10.1016/S0014-4800(03)00012-1 .

Notes and References

1. Web site: Entrez Gene: MFI2 antigen p97 (melanoma associated) identified by monoclonal antibodies 133.2 and 96.5.