title: The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin.
abstract: The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC- cobalamin (Cbl) and internalizes the complex by endocytosis. This receptor was purified from human placental membranes by affinity chromatography. Tryptic digest of the protein extracted from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel and subjected to liquid chromatography/mass spectrometry identified 4 peptides that matched with a membrane protein in the data bank. TCblR belongs to the low-density lipoprotein receptor family, with 2 low-density lipoprotein receptor type A domains separated by a complement-like cysteine-rich region. The 282-amino acid sequence includes a signal peptide of 31 residues, extracellular domain of 198 residues, a transmembrane region of 21 residues, and a cytoplasmic domain of 32 residues. The binding of TC-Cbl does not require the cytoplasmic domain or its orientation in the plasma membrane because the recombinant extracellular domain binds TC-Cbl with high affinity and specificity. The protein is heavily glycosylated and accounts for the 58-kDa size by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The human gene first identified as 8D6A and more recently as CD 320 encoding TCblR is located at p13.2 on the short arm of chromosome 19, spans a length of 6.224 kb, and is composed of 5 exons and 4 introns.
authors.affiliation: Departments of Medicine and Cell Biology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. Edward.Quadros@downstate.edu
authors.forename: Edward V
authors.initials: EV
authors.lastname: Quadros
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D004705:Endocytosis / Q000502:physiology; D005260:Female; D006801:Humans; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014155:Transcobalamins / Q000378:metabolism*; D014162:Transfection; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014155:Transcobalamins; C028176:transcobalamin receptor; D014805:Vitamin B 12
references.citation: Arch Biochem Biophys. 2003 Mar 15;411(2):204-14
references.pmid: 12623069
references.citation: Nature. 1961 Jul 22;191:393-5
references.pmid: 13695298
references.citation: J Immunol. 2001 Jul 1;167(1):49-56
references.pmid: 11418631
references.citation: Vitam Horm. 1970;28:415-40
references.pmid: 4947477
references.citation: J Biol Chem. 1991 Apr 25;266(12):7860-3
references.pmid: 1708393
references.citation: J Membr Biol. 2003 May 1;193(1):57-66
references.pmid: 12879166
references.citation: J Biol Chem. 1995 Apr 7;270(14):8152-7
references.pmid: 7713919
references.citation: J Biol Chem. 1997 Feb 7;272(6):3538-43
references.pmid: 9013602
references.citation: Arch Biochem Biophys. 1994 Jan;308(1):192-9
references.pmid: 8311452
references.citation: Br Med J. 1978 Jun 3;1(6125):1453-5
references.pmid: 647333
references.citation: J Biol Chem. 1978 Mar 25;253(6):1766-72
references.pmid: 632241
references.citation: J Biol Chem. 1986 Nov 25;261(33):15455-60
references.pmid: 3782074
references.citation: Arch Biochem Biophys. 1975 Jun;168(2):386-93
references.pmid: 237480
references.citation: Baillieres Clin Haematol. 1995 Sep;8(3):499-514
references.pmid: 8534959
references.citation: Blood. 2004 Aug 1;104(3):815-21
references.pmid: 15090445
references.citation: J Biol Chem. 1997 Aug 15;272(33):20920-8
references.pmid: 9252420
references.citation: Bioconjug Chem. 1996 Mar-Apr;7(2):217-32
references.pmid: 8983344
references.citation: Am J Physiol. 1999 Jul;277(1):G161-6
references.pmid: 10409163
references.citation: Exp Cell Res. 1979 Jan;118(1):127-34
references.pmid: 759210
references.citation: Blood. 1995 May 15;85(10):2711-9
references.pmid: 7742531
references.citation: Blood. 1990 Oct 1;76(7):1380-6
references.pmid: 2169922
references.citation: J Biol Chem. 1996 May 17;271(20):11718-25
references.pmid: 8662615
references.citation: Biochem Biophys Res Commun. 2005 Feb 25;327(4):1006-10
references.pmid: 15652495
references.citation: Blood. 1993 Mar 1;81(5):1239-45
references.pmid: 8443384
references.citation: Biochim Biophys Acta. 1995 Jun 9;1244(2-3):395-403
references.pmid: 7599160
references.citation: Methods Enzymol. 1986;123:28-36
references.pmid: 3702721
references.citation: Methods Enzymol. 1997;281:281-9
references.pmid: 9250992
references.citation: Am J Physiol. 1989 Feb;256(2 Pt 1):C296-303
references.pmid: 2493194
references.citation: J Biol Chem. 1996 Feb 23;271(8):4195-200
references.pmid: 8626762
references.citation: J Exp Med. 2000 Mar 20;191(6):1077-84
references.pmid: 10727470