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J Biol Chem, Vol. 274, Issue 30, 20826-20832, July 23, 1999
From the Cedars-Sinai Medical Center, Department of Medicine,
Division of Hematology/Oncology, Burns and Allen Research Institute,
University of California Los Angeles School of Medicine, Los Angeles,
California 90048
Transferrin receptor (TfR) plays a major role in
cellular iron uptake through binding and internalizing a carrier
protein transferrin (Tf). We have cloned, sequenced, and mapped a human gene homologous to TfR, termed TfR2. Two
transcripts were expressed from this gene: 
(~2.9 kilobase pairs),
and 
(~2.5 kilobase pairs). The predicted amino acid sequence
revealed that the TfR2- protein was a type II membrane protein and
shared a 45% identity and 66% similarity in its extracellular domain
with TfR. The TfR2- protein lacked the amino-terminal portion of the
TfR2- protein including the putative transmembrane domain. Northern
blot analysis showed that the transcript was predominantly
expressed in the liver. In addition, high expression occurred in K562,
an erythromegakaryocytic cell line. To analyze the function of TfR2,
Chinese hamster ovary TfR-deficient cells (CHO-TRVb cells) were stably
transfected with FLAG-tagged TfR2-. These cells showed an increase
in biotinylated Tf binding to the cell surface, which was competed by
nonlabeled Tf, but not by lactoferrin. Also, these cells had a marked
increase in Tf-bound 55Fe uptake. Taken together,
TfR2- may be a second transferrin receptor that can mediate cellular
iron transport.
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|
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|
|
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