Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice.
Hephaestin (Hp) plays an important role in intestinal iron absorption and is predicted to be a ferroxidase based on significant sequence identity to the serum multicopper ferroxidase ceruloplasmin. Here, we demonstrate that Hp has both amine oxidase and ferroxidase activity in cultured cells and primary intestinal enterocytes with the use of both gel and solution assays. The specificity of the activity is shown by immunoblotting, immunoprecipitation, and immunodepletion experiments. Surprisingly, the truncated hephaestin expressed in sex-linked anemia (sla) mice still has measurable, but decreased, oxidase activity. Molecular modeling of the truncated hephaestin suggests retention of a minimum catalytic core required for enzymatic activity. We suggest that hephaestin, by way of its ferroxidase activity, facilitates iron export from intestinal enterocytes, most likely in cooperation with the basolateral iron transporter, Ireg1.
Chen
Huijun
H
Department of Nutrition and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Attieh
Zouhair K
ZK
Su
Trent
T
Syed
Basharut A
BA
Gao
Hua
H
Alaeddine
Rima M
RM
Fox
Tama C
TC
Usta
Julnar
J
Naylor
Claire E
CE
Evans
Robert W
RW
McKie
Andrew T
AT
Anderson
Gregory J
GJ
Vulpe
Chris D
CD
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000595:Amino Acid Sequence; D000740:Anemia / Q000235:genetics*; D000818:Animals; D020134:Catalytic Domain; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000378:metabolism*; D020895:Enterocytes / Q000201:enzymology / Q000378:metabolism; D040181:Genetic Diseases, X-Linked; D007501:Iron / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D017384:Sequence Deletion
C117324:Heph protein, mouse; D008565:Membrane Proteins; D007501:Iron; D002570:Ceruloplasmin; D006631:Amine Oxidase (Copper-Containing)