Hephaestin

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Hephaestin
Identifiers
Symbol HEPH
Alt. symbols KIAA0698, CPL
Entrez 9843
HUGO 4866
OMIM 300167
RefSeq NM_138737
UniProt Q9BQS7
Other data
Locus Chr. X q11-q12

Hephaestin also known as HEPH is a protein which in humans is encoded by the HEPH gene.[1][2][3]

Function[edit]

Hephaestin is involved in the metabolism and homeostasis of iron and possibly copper.[4] 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.[5]

Discovery[edit]

Hephaestin was first identified by Dr. Christopher D. Vulpe of the University of California, Berkeley in 1999.[2] They named the newfound 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.[6] 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 Km of 2.1 μM for Fe(II).

See also[edit]

References[edit]

  1. ^ Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (June 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID 9734811. 
  2. ^ a b Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ (February 1999). "Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse". Nat. Genet. 21 (2): 195–9. doi:10.1038/5979. PMID 9988272. 
  3. ^ "Entrez Gene: Hephaestin". 
  4. ^ Chen H, Huang G, Su T, Gao H, Attieh ZK, McKie AT, Anderson GJ, Vulpe CD (May 2006). "Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency". J. Nutr. 136 (5): 1236–41. PMID 16614410. 
  5. ^ Chen H, Attieh ZK, Su T, Syed BA, Gao H, Alaeddine RM, Fox TC, Usta J, Naylor CE, Evans RW, McKie AT, Anderson GJ, Vulpe CD (May 2004). "Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice". Blood 103 (10): 3933–9. doi:10.1182/blood-2003-09-3139. PMID 14751926. 
  6. ^ Griffiths TA, Mauk AG, MacGillivray RT (November 2005). "Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity". Biochemistry 44 (45): 14725–31. doi:10.1021/bi051559k. PMID 16274220.