The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin.
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.
Quadros
Edward V
EV
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
Nakayama
Yasumi
Y
Sequeira
Jeffrey M
JM
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*
D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014155:Transcobalamins; C028176:transcobalamin receptor; D014805:Vitamin B 12
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