Hephaestin

protein
Name = Hephaestin
caption =


width =
HGNCid = 4866
Symbol = HEPH
AltSymbols =
EntrezGene = 9843
OMIM = 300167
RefSeq =
UniProt = Q9BQS7
PDB =
ECnumber =
Chromosome = X
Arm = q
Band = 11-12
LocusSupplementaryData =

Hephaestin is a protein involved in the metabolism and homeostasis of iron and possibly copper. It is a transmembrane copper-dependent ferroxidase responsible for transporting dietary iron from intestinal enterocytes into the circulatory system. The highest expression of hephaestin is found in small intestine. It is limited to enterocytes of the villi (where the iron absorption takes place), being almost absent in crypt cells. Hephaestin converts iron(II) state, Fe²⁺ to iron(III) state, Fe³⁺ and mediates iron efflux most likely in cooperation with the basolateral iron transporter, "ferroportin 1". To a lesser extent hephaestin has been detected in colon, spleen, kidney, breast, placenta and bone trabecular cells but its role in these tissues remains to be established. Hephaestin presents homology with ceruloplasmin, a serum dehydrogenase protein involved in copper detoxification and storage.

Hephaestin is a protein of 1135 aminoacids formed from a precursor of 1158 aminoacids and is 130.4 kDa. It is predicted to bind 6 copper ions per monomer.

Hephaestin was first identified by Dr. Christopher D. Vulpe of the University of California, Berkeley in 1999 [ [http://www.nature.com/ng/journal/v21/n2/abs/ng0299_195.html Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. "Nature Genetics" 1999 Feb;21(2):195-9.] ] . They named the new found protein after Hephaestus, the Greek god of metal working.

Human hephaestin, lacking the putative transmembrane domain, was first recombinantly expressed in 2005 by Drs. Tanya Griffiths, Grant Mauk, and Ross MacGillivray at the University of British Columbia [ [http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2005/44/i45/abs/bi051559k.html Griffiths TAM, Mauk AG, MacGillivray RTA. Recombinant Expression and Functional Characterization of Human Hephaestin: A Multicopper Oxidase with Ferroxidase Activity. "Biochemistry" 2005 Oct; 44(45):14725 -14731.] ] . They demonstrated that recombinant human hephaestin (rhHp) bound copper (determined by inductively coupled plasma mass spectrometry) and exhibited an absorption maximum at ~610 nm consistent with other blue multicopper oxidases such as ceruloplasmin. By using ferrous ammonium sulfate as a substrate, rhHp was shown to have ferroxidase activity with a K_m of 2.1 μM for Fe(II).

ee also

*Human iron metabolism
*Ceruloplasmin

References