Editing Transferrin (section)

== Occurrence and function ==

Transferrins are glycoproteins that are often found in biological fluids of vertebrates. When a transferrin protein loaded with iron encounters a [[transferrin receptor]] on the surface of a [[cell (biology)|cell]], e.g., erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a [[vesicle (biology)|vesicle]] by [[receptor-mediated endocytosis]].<ref name="Halbrooks_2003">{{cite journal | vauthors = Halbrooks PJ, He QY, Briggs SK, Everse SJ, Smith VC, MacGillivray RT, Mason AB | title = Investigation of the mechanism of iron release from the C-lobe of human serum transferrin: mutational analysis of the role of a pH sensitive triad | journal = Biochemistry | volume = 42 | issue = 13 | pages = 3701–7 | date = April 2003 | pmid = 12667060 | doi = 10.1021/bi027071q }}</ref> The pH of the vesicle is reduced by hydrogen ion pumps ([[V-ATPase|{{chem|H|+}} ATPases]]) to about 5.5, causing transferrin to release its iron ions.<ref name="MacGillivray_1998" /> Iron release rate is dependent on several factors including pH levels, interactions between lobes, temperature, salt, and chelator.<ref name="Halbrooks_2003" /> The receptor with its [[ligand]] bound transferrin is then transported through the [[endocytic cycle]] back to the cell surface, ready for another round of iron uptake.
Each transferrin molecule has the ability to carry two iron ions in the [[ferric]] form ({{chem|Fe|3+}}).<ref name="Baker_1992" />

=== Humans and other mammals ===
The [[liver]] is the main site of transferrin synthesis but other tissues and organs, including the brain, also produce transferrin. A major source of transferrin secretion in the brain is the [[choroid plexus]] in the [[ventricular system]].<ref name="Moos">{{cite journal | vauthors = Moos T | title = Brain iron homeostasis | journal = Danish Medical Bulletin | volume = 49 | issue = 4 | pages = 279–301 | date = November 2002 | pmid = 12553165 }}</ref> The main role of transferrin is to deliver iron from absorption centers in the [[duodenum]] and white blood cell [[macrophages]] to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur.<ref name="pmid18473900" /> The receptor helps maintain iron [[homeostasis]] in the cells by controlling iron concentrations.<ref name="pmid18473900" />

The [[gene]] coding for transferrin in humans is located in [[chromosome]] band 3q21.<ref name="pmid6585826" />

Medical professionals may check serum transferrin level in [[Iron deficiency (medicine)|iron deficiency]] and in [[iron overload disorder]]s such as [[hemochromatosis]].

=== Other species ===
''[[Drosophila melanogaster]]'' has three transferrin genes and is highly divergent from all other model clades, ''[[Ciona intestinalis]]'' one, ''[[Danio rerio]]'' has three highly divergent from each other, as do ''[[Takifugu rubripes]]'' and ''[[Xenopus tropicalis]]'' and ''[[Gallus gallus]]'', while ''[[Monodelphis domestica]]'' has two divergent [[ortholog]]s, and ''[[Mus musculus]]'' has two relatively close and one more distant ortholog. Relatedness and orthology/[[paralog]]y data are also available for ''[[Dictyostelium discoideum]]'', ''[[Arabidopsis thaliana]]'', and ''[[Pseudomonas aeruginosa]]''.<ref name="Gabaldon-Koonin-2013">{{cite journal | vauthors = Gabaldón T, Koonin EV | title = Functional and evolutionary implications of gene orthology | journal = Nature Reviews. Genetics | volume = 14 | issue = 5 | pages = 360–6 | date = May 2013 | pmid = 23552219 | doi = 10.1038/nrg3456 | publisher = [[Nature Portfolio]] | author2-link = Eugene Koonin | pmc = 5877793 }}</ref>