Hephaestin also known as HEPH is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the HEPH gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Function

Hephaestin is involved in the metabolism and homeostasis of iron

Iron

Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 and possibly copper

Copper

Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

. It is a transmembrane copper-dependent ferroxidase

Ferroxidase

Ferroxidase also known as Fe:oxygen oxidoreductase is an enzyme that catalyzes the oxidization of iron II to iron III:- Examples :Human genes encoding proteins with ferroxidase activity include:* CP – Ceruloplasmin* FTH1 – Ferritin heavy chain...

 responsible for transporting dietary iron from intestinal enterocyte

Enterocyte

Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...

s into the circulatory system. The highest expression of hephaestin is found in small intestine

Small intestine

The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

. It is limited to enterocytes of the villi

Villus

Intestinal villi are tiny, finger-like projections that protrude from the epithelial lining of the intestinal wall. Each villus is approximately 0.5-1.6 mm in length and has many microvilli , each of which are much smaller than a single villus...

 (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

Ceruloplasmin

Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...

, 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

Atomic mass unit

The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

. It is predicted to bind 6 copper ions per monomer.

Discovery

Hephaestin was first identified by Dr. Christopher D. Vulpe of the University of California, Berkeley in 1999. They named the new found protein after Hephaestus

Hephaestus

Hephaestus was a Greek god whose Roman equivalent was Vulcan. He is the son of Zeus and Hera, the King and Queen of the Gods - or else, according to some accounts, of Hera alone. He was the god of technology, blacksmiths, craftsmen, artisans, sculptors, metals, metallurgy, fire and volcanoes...

, 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. 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

Multicopper oxidase

In molecular biology, multicopper oxidases are enzymes which oxidise their substrate by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced to two...

 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).