Journal of Molecular Evolution

, Volume 64, Issue 1, pp 113–128

Molecular Evolution of the Transferrin Receptor/Glutamate Carboxypeptidase II Family



The transferrin receptor family is represented by at least seven different homologous proteins in primates. Transferrin receptor (TfR1) is a type II membrane glycoprotein that, as a cell surface homodimer, binds iron-loaded transferrin as part of the process of iron transfer and uptake. Other family members include transferrin receptor 2 (TfR2), glutamate carboxypeptidase II (GCP2 or PSMA), N-acetylated α-linked acidic dipeptidase-like protein (NLDL), N-acetylated α-linked acidic dipeptidase 2 (NAALAD2), and prostate-specific membrane antigen-like protein (PMSAL/GCPIII). We compared 86 different sequences from 24 different species, from mammals to fungi. Through this comparison, we have identified several highly conserved residues specific to each family not previously associated with clinical mutations. The evolutionary history of the TfR/GCP2 family shows repeated episodes of duplications consistent with recent theories that nondispensable, slowly evolving genes are more likely to form multiple gene families.


Transferrin receptor Glutamate carboxypeptidase II Glutamate carboxypeptidase II N-Acetylated α-linked acidic dipiptidase 2 Gene duplicationI Iron homeostasis 


  1. Altschul S, Madden T, Schaffer A, Zhang J, Zhang Z, Miller W, Lipman D (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402PubMedGoogle Scholar
  2. Alvarez E, Girones N, Davis RJ (1989) Intermolecular disulfide bonds are not required for the expression of the dimeric state and functional activity of the transferrin receptor. EMBO J 8:2231–2240PubMedGoogle Scholar
  3. Alvarez E, Girones N, Davis RJ (1990a) Inhibition of the receptor-mediated endocytosis of diferric transferrin is associated with the covalent modification of the transferrin receptor with palmitic acid. J Biol Chem 265:16644–16655Google Scholar
  4. Alvarez E, Girones N, Davis RJ (1990b) A point mutation in the cytoplasmic domain of the transferrin receptor inhibits endocytosis. Biochem J 267:31–35Google Scholar
  5. Amores A, Force A, Yan YL, Joly L, Amemiya C, Fritz A, Ho RK, Langeland J, Prince V, Wang YL, Westerfield M, Ekker M, Postlethwait JH (1998) Zebrafish hox clusters and vertebrate genome evolution. Science 282:1711–1714PubMedGoogle Scholar
  6. Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795PubMedGoogle Scholar
  7. Bennett MJ, Lebron JA, Bjorkman PJ (2000) Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature 403:46–53PubMedGoogle Scholar
  8. Bruns CM, Nowalk AJ, Arvai AS, McTigue MA, Vaughan KG, Mietzner TA, McRee DE (1997) Structure of Haemophilus influenzae Fe(+3)-binding protein reveals convergent evolution within a superfamily. Nat Struct Biol 4:919–924PubMedGoogle Scholar
  9. Bruns CM, Anderson DS, Vaughan KG, Williams PA, Nowalk AJ, McRee DE, Mietzner TA (2001) Crystallographic and biochemical analyses of the metal-free Haemophilus influenzae Fe3+-binding protein. Biochemistry 40:15631–15637PubMedGoogle Scholar
  10. Buchegger F, Trowbridge IS, Liu LF, White S, Collawn JF (1996) Functional analysis of human/chicken transferrin receptor chimeras indicates that the carboxy-terminal region is important for ligand binding. Eur J Biochem 235:9–17PubMedGoogle Scholar
  11. Calzolari A, Deaglio S, Sposi NM, Petrucci E, Morsilli O, Gabbianelli M, Malavasi F, Peschle C, Testa U (2004) Transferrin receptor 2 protein is not expressed in normal erythroid cells. Biochem J 381:629–634PubMedGoogle Scholar
  12. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P (2000) The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25:14–15PubMedGoogle Scholar
  13. Carter RE, Feldman AR, Coyle JT (1996) Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc Natl Acad Sci USA 93:749–753PubMedGoogle Scholar
  14. Cheng Y, Mason AB, Woodworth RC (1995) pH dependence of specific divalent anion binding to the N-lobe of recombinant human transferrin. Biochemistry 34:14879–14884PubMedGoogle Scholar
  15. Collawn JF, Stangel M, Kuhn LA, Esekogwu V, Jing SQ, Trowbridge IS, Tainer JA (1990) Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis. Cell 63:1061–1072PubMedGoogle Scholar
  16. Collawn JF, Lai A, Domingo D, Fitch M, Hatton S, Trowbridge IS (1993) YTRF is the conserved internalization signal of the transferrin receptor, and a second YTRF signal at position 31–34 enhances endocytosis. J Biol Chem 268:21686–21692PubMedGoogle Scholar
  17. Cornelissen CN (2003) Transferrin–iron uptake by Gram–negative bacteria. Front Biosci 8:d836–d847PubMedGoogle Scholar
  18. Davis JC, Petrov DA (2004) Preferential duplication of conserved proteins in eukaryotic genomes. PLoS Biol 2:E55PubMedGoogle Scholar
  19. Davis MI, Bennett MJ, Thomas LM, Bjorkman PJ (2005) Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proc Natl Acad Sci USA 102:5981–5986PubMedGoogle Scholar
  20. Devlin AM, Ling EH, Peerson JM, Fernando S, Clarke R, Smith AD, Halsted CH (2000) Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Hum Mol Genet 9:2837–2844PubMedGoogle Scholar
  21. Dubljevic V, Sali A, Goding JW (1999) A conserved RGD (Arg-Gly-Asp) motif in the transferrin receptor is required for binding to transferrin. Biochem J 341(Pt 1):11–14PubMedGoogle Scholar
  22. Dunkov B, Georgieva T (2006) Insect iron binding proteins: insights from the genomes. Insect Biochem Mol Biol 36:300–309PubMedGoogle Scholar
  23. Ebner B, Burmester T, Hankeln T (2003) Globin genes are present in Ciona intestinalis. Mol Biol Evol 20:1521–1525PubMedGoogle Scholar
  24. Elgamal AA, Holmes EH, Su SL, Tino WT, Simmons SJ, Peterson M, Greene TG, Boynton AL, Murphy GP (2000) Prostate-specific membrane antigen (PSMA): current benefits and future value. Semin Surg Oncol 18:10–16PubMedGoogle Scholar
  25. Evans P, Kemp J (1997) Exon/intron structure of the human transferrin receptor gene. Gene 199:123–131PubMedGoogle Scholar
  26. Fleming RE, Ahmann JR, Migas MC, Waheed A, Koeffler HP, Kawabata H, Britton RS, Bacon BR, Sly WS (2002) Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci USA 99:10653–10658PubMedGoogle Scholar
  27. Fodinger M, Dierkes J, Skoupy S, Rohrer C, Hagen W, Puttinger H, Hauser AC, Vychytil A, Sunder-Plassmann G (2003) Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients. J Am Soc Nephrol 14:1314–1319PubMedGoogle Scholar
  28. Ghadge GD, Slusher BS, Bodner A, Canto MD, Wozniak K, Thomas AG, Rojas C, Tsukamoto T, Majer P, Miller RJ, Monti AL, Roos RP (2003) Glutamate carboxypeptidase II inhibition protects motor neurons from death in familial amyotrophic lateral sclerosis models. Proc Natl Acad Sci USA 100:9554–9559PubMedGoogle Scholar
  29. Ghose S, Weickert CS, Colvin SM, Coyle JT, Herman MM, Hyde TM, Kleinman JE (2004) Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophrenia. Neuropsychopharmacology 29:117–125PubMedGoogle Scholar
  30. Giannetti AM, Snow PM, Zak O, Bjorkman PJ (2003) Mechanism for multiple ligand recognition by the human transferrin receptor. PLoS Biol 1:E51PubMedGoogle Scholar
  31. Girelli D, Bozzini C, Roetto A, Alberti F, Daraio F, Colombari R, Olivieri O, Corrocher R, Camaschella C (2002) Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology 122:1295–1302PubMedGoogle Scholar
  32. Goswami T, Andrews NC (2006) Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem 39:28494–28498Google Scholar
  33. Griffiths WJ, Cox TM (2003) Co-localization of the mammalian hemochromatosis gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells. J Histochem Cytochem 51:613–624PubMedGoogle Scholar
  34. Hayes GR, Enns CA, Lucas JJ (1992) Identification of the O-linked glycosylation site of the human transferrin receptor. Glycobiology 2:355–359PubMedGoogle Scholar
  35. Helliwell CA, Chin-Atkins AN, Wilson IW, Chapple R, Dennis ES, Chaudhury A (2001) The Arabidopsis AMP1 gene encodes a putative glutamate carboxypeptidase. Plant Cell 13:2115–2125PubMedGoogle Scholar
  36. Heston WD, (1997) Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. Urology 49:104–112PubMedGoogle Scholar
  37. Horoszewicz JS, Kawinski E, Murphy GP (1987) Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 7:927–935PubMedGoogle Scholar
  38. Horvath JE, Gulden CL, Vallente RU, Eichler MY, Ventura M, McPherson JD, Graves TA, Wilson RK, Schwartz S, Rocchi M, Eichler EE (2005) Punctuated duplication seeding events during the evolution of human chromosome 2p11. Genome Res 15:914–927PubMedGoogle Scholar
  39. Hueffer K, Parker JS, Weichert WS, Geisel RE, Sgro JY, Parrish CR (2003) The natural host range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferrin receptor. J Virol 77:1718–1726PubMedGoogle Scholar
  40. Immesberger A, Burmester T (2004) Putative phenoloxidases in the tunicate Ciona intestinalis and the origin of the arthropod hemocyanin superfamily. J Comp Physiol [B] 174:169–180Google Scholar
  41. Israeli RS, Powell CT, Fair WR, Heston WD (1993) Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res 53:227–230PubMedGoogle Scholar
  42. Jing SQ, Trowbridge IS (1987) Identification of the intermolecular disulfide bonds of the human transferrin receptor and its lipid-attachment site. EMBO J 6:327–331PubMedGoogle Scholar
  43. Julenius K, Molgaard A, Gupta R, Brunak S (2005) Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites. Glycobiology 15:153–164PubMedGoogle Scholar
  44. Kaup M, Dassler K, Weise C, Fuchs H (2002) Shedding of the transferrin receptor is mediated constitutively by an integral membrane metalloprotease sensitive to tumor necrosis factor alpha protease inhibitor-2. J Biol Chem 277:38494–38502PubMedGoogle Scholar
  45. Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, Gombart AF, Koeffler HP (1999) Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 274:20826–20832PubMedGoogle Scholar
  46. Kawabata H, Germain RS, Vuong PT, Nakamaki T, Said JW, Koeffler HP (2000) Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J Biol Chem 275:16618–16625PubMedGoogle Scholar
  47. Kawabata H, Germain RS, Ikezoe T, Tong X, Green EM, Gombart AF, Koeffler HP (2001) Regulation of expression of murine transferrin receptor 2. Blood 98:1949–1954PubMedGoogle Scholar
  48. Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M (2005) Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci USA 102:1324–1328PubMedGoogle Scholar
  49. Kohgo Y, Nishisato T, Kondo H, Tsushima N, Niitsu Y, Urushizaki I (1986) Circulating transferrin receptor in human serum. Br J Haematol 64:277–281PubMedGoogle Scholar
  50. Koyama C, Wakusawa S, Hayashi H, Suzuki R, Yano M, Yoshioka K, Kozuru M, Takayamam Y, Okada T, Mabuchi H (2005) Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis. Haematologica 90:302–307PubMedGoogle Scholar
  51. Kumar S, Tamura K, Nei M (2004) MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163PubMedGoogle Scholar
  52. Lambert LA, Perri H, Meehan TJ (2005) Evolution of duplications in the transferrin family of proteins. Comp Biochem Physiol B Biochem Mol Biol 140:11–25PubMedGoogle Scholar
  53. Lapidus RG, Tiffany CW, Isaacs JT, Slusher BS (2000) Prostate-specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells. Prostate 45:350–354PubMedGoogle Scholar
  54. Lawrence CM, Ray S, Babyonyshev M, Galluser R, Borhani DW, Harrison SC (1999) Crystal structure of the ectodomain of human transferrin receptor. Science 286:779–782PubMedGoogle Scholar
  55. Lee PL, Barton JC (2006) Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. Acta Haematol 115:102–105PubMedGoogle Scholar
  56. Le Gac G, Ferec C (2005) The molecular genetics of haemochromatosis. Eur J Hum Genet 13:1172–1185PubMedGoogle Scholar
  57. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC (1999) Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet 21:396–399PubMedGoogle Scholar
  58. Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155PubMedGoogle Scholar
  59. Mahadevan D, Saldanha JW (1999) The extracellular regions of PSMA and the transferrin receptor contain an aminopeptidase domain: implications for drug design. Protein Sci 8:2546–2549PubMedGoogle Scholar
  60. Mahon P, Bateman A (2000) The PA domain: a protease-associated domain. Protein Sci 9:1930–1934PubMedCrossRefGoogle Scholar
  61. Makalowski W (2001) Are we polyploids? A brief history of one hypothesis. Genome Res 11:667–670PubMedGoogle Scholar
  62. 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 (2002) Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood 100:1075–1077PubMedGoogle Scholar
  63. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093PubMedGoogle Scholar
  64. Nicholas K, Nicholas HJ, Deerfield DI (1997) GeneDoc: analysis and visualization of genetic variation. EMBNEW NEWS 4:14Google Scholar
  65. O’Keefe DS, Su SL, Bacich DJ, Horiguchi Y, Luo Y, Powell CT, Zandvliet D, Russell PJ, Molloy PL, Nowak NJ, Shows TB, Mullins C, Vonder Haar RA, Fair WR, Heston WD (1998) Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. Biochim Biophys Acta 1443:113–127PubMedGoogle Scholar
  66. O’Keefe DS, Bacich DJ, Heston WD (2004) Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene. Prostate 58:200–210PubMedGoogle Scholar
  67. Odorizzi G, Trowbridge IS (1997) Structural requirements for basolateral sorting of the human transferrin receptor in the biosynthetic and endocytic pathways of Madin-Darby canine kidney cells. J Cell Biol 137:1255–1264PubMedGoogle Scholar
  68. Ohno S (1970) Evolution by gene duplication. Springer-Verlag, BerlinGoogle Scholar
  69. Ohno S (1993) Patterns in genome evolution. Curr Opin Genet Dev 3:911–914PubMedGoogle Scholar
  70. Palermo LM, Hueffer K, Parrish CR (2003) Residues in the apical domain of the feline and canine transferrin receptors control host-specific binding and cell infection of canine and feline parvoviruses. J Virol 77:8915–8923PubMedGoogle Scholar
  71. Pangalos MN, Neefs JM, Somers M, Verhasselt P, Bekkers M, van der Helm L, Fraiponts E, Ashton D, Gordon RD (1999) Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. J Biol Chem 274:8470–8483PubMedGoogle Scholar
  72. Park CH, Valore EV, Waring AJ, Ganz T (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810PubMedGoogle Scholar
  73. Parker JS, Murphy WJ, Wang D, O’Brien SJ, Parrish CR (2001) Canine and feline parvoviruses can use human or feline transferrin receptors to bind, enter, and infect cells. J Virol 75:3896–3902PubMedGoogle Scholar
  74. Parkkila S, Waheed A, Britton RS, Bacon BR, Zhou XY, Tomatsu S, Fleming RE, Sly WS (1997) Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 94:13198–13202PubMedGoogle Scholar
  75. Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B, Heston WD (1996) Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res 2:1445–1451PubMedGoogle Scholar
  76. Rajasekaran SA, Anilkumar G, Oshima E, Bowie JU, Liu H, Heston W, Bander NH, Rajasekaran AK (2003) A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol Biol Cell 14:4835–4845PubMedGoogle Scholar
  77. Rawlings ND, Barrett AJ (1995) Evolutionary families of metallopeptidases. Methods Enzymol 248:183–228PubMedCrossRefGoogle Scholar
  78. Relton CL, Wilding CS, Jonas PA, Lynch SA, Tawn EJ, Burn J (2003) Genetic susceptibility to neural tube defect pregnancy varies with offspring phenotype. Clin Genet 64:424–428PubMedGoogle Scholar
  79. Riegert P, Wanner V, Bahram S (1998) Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene. J Immunol 161:4066–4077PubMedGoogle Scholar
  80. Robb AD, Ericsson M, Wessling–Resnick M (2004) Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies. Am J Physiol Cell Physiol 287:C1769–C1775PubMedGoogle Scholar
  81. Roetto A, Totaro A, Piperno A, Piga A, Longo F, Garozzo G, Cali A, De Gobbi M, Gasparini P, Camaschella C (2001) New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood 97:2555–2560PubMedGoogle Scholar
  82. Rutledge EA, Green FA, Enns CA (1994a) Generation of the soluble transferrin receptor requires cycling through an endosomal compartment. J Biol Chem 269:31864–31868Google Scholar
  83. Rutledge EA, Root BJ, Lucas JJ, Enns CA (1994b) Elimination of the O-linked glycosylation site at Thr 104 results in the generation of a soluble human-transferrin receptor. Blood 83:580–586Google Scholar
  84. Shih YJ, Baynes RD, Hudson BG, Flowers CH, Skikne BS, Cook JD (1990) Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem 265:19077–19081PubMedGoogle Scholar
  85. Shneider BL, Thevananther S, Moyer MS, Walters HC, Rinaldo P, Devarajan P, Sun AQ, Dawson PA, Ananthanarayanan M (1997) Cloning and characterization of a novel peptidase from rat and human ileum. J Biol Chem 272:31006–31015PubMedGoogle Scholar
  86. Sonnhammer EL, von Heijne G, Krogh A (1998) A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol 6:175–182PubMedGoogle Scholar
  87. Speno HS, Luthi-Carter R, Macias WL, Valentine SL, Joshi AR, Coyle JT (1999) Site-directed mutagenesis of predicted active site residues in glutamate carboxypeptidase II. Mol Pharmacol 55:179–185PubMedGoogle Scholar
  88. Steverding D, Stierhof YD, Fuchs H, Tauber R, Overath P (1995) Transferrin-binding protein complex is the receptor for transferrin uptake in Trypanosoma brucei. J Cell Biol 131:1173–1182PubMedGoogle Scholar
  89. Stimpson HE, Lewis MJ, Pelham HR (2006) Transferrin receptor-like proteins control the degradation of a yeast metal transporter. EMBO J 25:662–672PubMedGoogle Scholar
  90. Subramaniam S (1998) The Biology Workbench––a seamless database and analysis environment for the biologist. Proteins 32:1–2PubMedGoogle Scholar
  91. Sullivan AL, Grasso JA, Weintraub LR (1976) Micropinocytosis of transferrin by developing red cells: an electron-microscopic study utilizing ferritin-conjugated transferrin and ferritin-conjugated antibodies to transferrin. Blood 47:133–143PubMedGoogle Scholar
  92. Tajima F (1993) Simple methods for testing the molecular evolutionary clock hypothesis. Genetics 135:599–607PubMedGoogle Scholar
  93. Thompson GJ, Crozier YC, Crozier RH (2003) Isolation and characterization of a termite transferrin gene up-regulated on infection. Insect Mol Biol 12:1–7PubMedGoogle Scholar
  94. Tonkin ET, Smith M, Eichhorn P, Jones S, Imamwerdi B, Lindsay S, Jackson M, Wang TJ, Ireland M, Burn J, Krantz ID, Carr P, Strachan T (2004) A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3. Hum Genet 115:139–148PubMedGoogle Scholar
  95. Troyer JK, Beckett ML, Wright GL Jr (1995) Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer 62:552–558PubMedGoogle Scholar
  96. Tsai G, Dunham KS, Drager U, Grier A, Anderson C, Collura J, Coyle JT (2003) Early embryonic death of glutamate carboxypeptidase II (NAALADase) homozygous mutants. Synapse 50:285–292PubMedGoogle Scholar
  97. Wessels HP, Geffen I, Spiess M (1989) A hepatocyte-specific basolateral membrane protein is targeted to the same domain when expressed in Madin-Darby canine kidney cells. J Biol Chem 264:17–20PubMedGoogle Scholar
  98. West AP Jr, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ (2000) Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 275:38135–38138PubMedGoogle Scholar
  99. West AP Jr, Giannetti AM, Herr AB, Bennett MJ, Nangiana JS, Pierce JR, Weiner LP, Snow PM, Bjorkman PJ (2001) Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites. J Mol Biol 313:385–397PubMedGoogle Scholar
  100. Wingert RA, Brownlie A, Galloway JL, Dooley K, Fraenkel P, Axe JL, Davidson AJ, Barut B, Noriega L, Sheng X, Zhou Y, Zon LI (2004) The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1. Development 131:6225–6235PubMedGoogle Scholar
  101. Yang S, Gu B, Xiao Z, Wang Y (1992) Analysis of the direction of fertility change for Chinese women. Chin J Popul Sci 4:105–118PubMedGoogle Scholar
  102. Yeh KY, Yeh M, Glass J (2004) Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. Am J Physiol Gastrointest Liver Physiol 286:G385–G394PubMedGoogle Scholar
  103. Zhang J, Qin S, Sait SN, Haley LL, Henry WM, Higgins MJ, Nowak NJ, Shows TB, Gerhard DS (2001) The pericentromeric region of human chromosome 11: evidence for a chromosome-specific duplication. Cytogenet Cell Genet 94:137–141PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of BiologyChatham CollegePittsburghUSA

Personalised recommendations