Transcobalamin receptor polypeptides, nucleic acids, and modulators thereof, and related methods of use in modulating cell growth and treating cancer and cobalamin deficiency

A method of identifying a modulator of cobalamin uptake into a cell, comprising:

• (a) contacting a cell comprising an exogenous polynucleotide that encodes a transcobalamin receptor polypeptide or a fragment thereof comprising the extracellular region of the transcobalamin receptor with transcobalamin in the presence of a candidate modulator;
• (b) determining an amount of the transcobalamin taken up by the cell;
• and
• (c) comparing the amount of transcobalamin taken up by the cell to an amount taken up in the absence of the candidate modulator,
• wherein a decreased or increased amount of transcobalamin taken up by the cell in the presence of the candidate modulator as compared to in the absence of the candidate modulator indicates that the candidate modulator is a modulator of cobalamin uptake into a cell.

A method of identifying a human antibody that inhibits cobalamin uptake into a cell, comprising:

• (a) contacting an isolated recombinantly-produced transcobalamin receptor polypeptide, or a fragment thereof comprising the extracellular region of the transcobalamin receptor, with transcobalamin in the presence of a human antibody specific for a transcobalamin receptor;
• (b) determining an amount of the transcobalamin bound to the transcobalamin receptor or fragment thereof;
• and
• (c) comparing the amount of bound transcobalamin to an amount bound in the absence of the antibody,
• wherein a decreased amount of bound transcobalamin in the presence of the antibody indicates that the antibody inhibits cobalamin uptake into a cell.

A method of identifying a human antibody that inhibits cobalamin uptake into a cell, comprising:

• (a) contacting a cell expressing an exogenous transcobalamin receptor polypeptide, or a fragment thereof comprising the extracellular region of the transcobalam receptor, with transcobalamin in the presence of a human antibody that specifically binds the transcobalamin receptor polypeptide;
• (b) determining an amount of the transcobalamin taken up by the cell;
• and
• (c) comparing the amount of transcobalamin taken up by the cell to an amount taken up in the absence of the antibody,
• wherein a decreased amount of transcobalamin taken up by the cell indicates that the antibody is an inhibitor of cobalamin uptake into a cell.