View source for Ferritin

{{Short description|Iron-carrying protein}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox protein family
| Symbol = Ferritin
| Name = Ferritin
| image = Ferritin.png
| width =
| caption = Structure of the murine ferritin complex<ref name="pmid12459904">{{PDB|1lb3}}; {{cite journal | vauthors = Granier T, Langlois d'Estaintot B, Gallois B, Chevalier JM, Précigoux G, Santambrogio P, Arosio P | title = Structural description of the active sites of mouse L-chain ferritin at 1.2 A resolution | journal = Journal of Biological Inorganic Chemistry | volume = 8 | issue = 1–2 | pages = 105–111 | date = January 2003 | pmid = 12459904 | doi = 10.1007/s00775-002-0389-4 | s2cid = 20756710 }}</ref>
| Pfam = PF00210
| Pfam_clan = CL0044
| InterPro = IPR008331
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1fha
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{infobox protein
| Name = [[Ferritin light chain|ferritin, light polypeptide]]
| caption =
| image =
| width =
| HGNCid = 3999
| Symbol = [[Ferritin light chain|FTL]]
| AltSymbols =
| EntrezGene = 2512
| OMIM = 134790
| RefSeq = NM_000146
| UniProt = P02792
| PDB =
| ECnumber=
| Chromosome = 19
| Arm = q
| Band = 13.3–13.4
| LocusSupplementaryData =
}}
{{infobox protein
| Name = [[FTH1|ferritin, heavy polypeptide 1]]
| caption =
| image =
| width =
| HGNCid = 3976
| Symbol = [[FTH1]]
| AltSymbols = FTHL6
| EntrezGene = 2495
| OMIM = 134770
| RefSeq = NM_002032
| UniProt = P02794
| PDB =
| ECnumber =
| Chromosome = 11
| Arm = q
| Band = 13
| LocusSupplementaryData =
}}
{{infobox protein
| Name = ferritin mitochondrial
| caption = Crystallographic structure of mitochondrial ferritin.<ref name="pmid15201052">{{PDB|1r03}}; {{cite journal | vauthors = Langlois d'Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Précigoux G, Levi S, Arosio P | title = Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala | journal = Journal of Molecular Biology | volume = 340 | issue = 2 | pages = 277–293 | date = July 2004 | pmid = 15201052 | doi = 10.1016/j.jmb.2004.04.036 }}</ref>
| image = Mitochondrial_Ferritin.png
| width =
| HGNCid = 17345
| Symbol = FTMT
| AltSymbols =
| EntrezGene = 94033
| OMIM = 608847
| RefSeq = NM_177478
| UniProt = Q8N4E7
| PDB =
| ECnumber =
| Chromosome = 5
| Arm = q
| Band = 23.1
| LocusSupplementaryData =
}}

'''Ferritin''' is a universal intracellular and extracellular [[protein]] that stores [[iron]] and releases it in a controlled fashion. The protein is produced by almost all living organisms, including [[archaea]], [[bacteria]], [[algae]], [[higher plants]], and [[animal]]s. It is the primary ''intracellular iron-storage protein'' in both [[prokaryote]]s and [[eukaryote]]s, keeping iron in a soluble and non-toxic form. In humans, it acts as a buffer against [[iron deficiency]] and [[iron overload]].<ref>{{Cite web |title=Iron Use and Storage in the Body: Ferritin and Molecular Representations |url=http://www.chemistry.wustl.edu/~edudev/LabTutorials/Ferritin/Ferritin.html |publisher=Department of Chemistry, [[Washington University in St. Louis]] |vauthors=Casiday R, Frey R}}</ref>

Ferritin is found in most tissues as a [[cytosol]]ic protein, but small amounts are secreted into the [[serum (blood)|serum]] where it functions as an iron carrier. Plasma ferritin is also an indirect [[biomarker|marker]] of the total amount of iron stored in the body; hence, serum ferritin is used as a [[diagnostic test]] for [[iron-deficiency anemia]] and [[iron overload]].<ref name="pmid20304033">{{cite journal | vauthors = Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV | title = Serum ferritin: Past, present and future | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1800 | issue = 8 | pages = 760–769 | date = August 2010 | pmid = 20304033 | pmc = 2893236 | doi = 10.1016/j.bbagen.2010.03.011 }}</ref> Aggregated ferritin transforms into a water insoluble, crystalline and amorphous form of storage iron called [[hemosiderin]].<ref>{{cite journal | vauthors = MacKenzie EL, Iwasaki K, Tsuji Y | title = Intracellular iron transport and storage: from molecular mechanisms to health implications | journal = Antioxidants & Redox Signaling | volume = 10 | issue = 6 | pages = 997–1030 | date = June 2008 | pmid = 18327971 | pmc = 2932529 | doi = 10.1089/ars.2007.1893 }}</ref>

Ferritin is a [[globular protein]] complex consisting of 24 [[protein subunit]]s forming a hollow spherical nanocage with multiple metal–protein interactions.<ref name="Theil2012">{{cite journal | vauthors = Theil EC | title = Ferritin protein nanocages-the story | journal = Nanotechnology Perceptions | volume = 8 | issue = 1 | pages = 7–16 | date = 2012 | pmid = 24198751 | pmc = 3816979 | doi = 10.4024/N03TH12A.ntp.08.01 }}</ref> Ferritin with iron removed is called '''apoferritin'''.<ref name = "Kresge_2004" >{{cite journal | vauthors = Kresge N, Simoni RD, Hill RL | title=The Characterization of Ferritin and Apoferritin by Leonor Michaelis and Sam Granick | journal=Journal of Biological Chemistry | publisher=Elsevier BV | volume=279 | issue=49 | year=2004 | issn=0021-9258 | doi=10.1016/s0021-9258(20)69471-6 | doi-access=free | pages=e9–e11}}</ref>{{rp|e10}}

== Gene ==

Ferritin genes are highly [[Conserved sequence|conserved]] between species. All vertebrate ferritin genes have three [[intron]]s and four [[exon]]s.<ref name="pmid11986201">{{cite journal | vauthors = Torti FM, Torti SV | title = Regulation of ferritin genes and protein | journal = Blood | volume = 99 | issue = 10 | pages = 3505–3516 | date = May 2002 | pmid = 11986201 | doi = 10.1182/blood.V99.10.3505 | doi-access = free }}</ref> In human ferritin, introns are present between [[amino acid]] [[Residue (chemistry)#Biochemistry|residue]]s 14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred [[untranslated region|untranslated base]]s at either end of the combined exons.<ref name=Theil1987/> The [[tyrosine]] residue at amino acid position 27 is thought to be associated with [[biomineralization]].<ref name="deZoysa2007">{{cite journal | vauthors = De Zoysa M, Lee J | title = Two ferritin subunits from disk abalone (Haliotis discus discus): cloning, characterization and expression analysis | journal = Fish & Shellfish Immunology | volume = 23 | issue = 3 | pages = 624–635 | date = September 2007 | pmid = 17442591 | doi = 10.1016/j.fsi.2007.01.013 | bibcode = 2007FSI....23..624D }}</ref>

== Protein structure ==

Ferritin is a hollow [[globular protein]] of mass 474&nbsp;[[Dalton (unit)|kDa]] and comprising 24 subunits. Typically it has internal and external diameters of about 8 and 12&nbsp;nm, respectively.<ref>{{Cite web |url=http://www.ugr.es/~josema/Structure.html |title=Ferritin Structure and Its Biomedical Implications |website=Metallic BioNano Particles |publisher=Universidad de Granada |archive-url=https://web.archive.org/web/20160827215820/http://www.ugr.es/~josema/Structure.html |archive-date=2016-08-27 |access-date=2016-01-16}}</ref> The nature of these subunits varies by class of organism:
* In [[vertebrate]]s, the subunits are of two types, [[Ferritin light chain|light (L)]] and [[FTH1|heavy (H)]], which have apparent molecular mass of 19&nbsp;kDa and 21&nbsp;kDa, respectively; their sequences are [[Sequence homology|homologous]] (about 50% identical).<ref name=Theil1987/>
* [[Amphibian]]s have an additional ("M") type of ferritin.<ref name=Andrews1992/>
* [[Plant]]s and [[bacteria]] have a single ferritin; it most closely resembles the vertebrate H-type.<ref name=Andrews1992/>
* In the [[gastropod]]s of the [[genus]] ''[[Lymnaea]]'', two types have been recovered, from [[somatic (biology)|somatic]] cells and the [[yolk]], respectively (see below).<ref name=Andrews1992/>
* In the pearl oyster ''[[Pinctada fucata]]'', an additional subunit resembling ''Lymnaea'' soma ferritin is associated with shell formation.<ref name="Zhang2003">{{cite journal | vauthors = Zhang Y, Meng Q, Jiang T, Wang H, Xie L, Zhang R | title = A novel ferritin subunit involved in shell formation from the pearl oyster (Pinctada fucata) | journal = Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology | volume = 135 | issue = 1 | pages = 43–54 | date = May 2003 | pmid = 12781972 | doi = 10.1016/S1096-4959(03)00050-2 }}</ref>
* In the parasite ''[[Schistosoma]]'', two types are present: one in males, the other in females.<ref name=Andrews1992/>

All the aforementioned ferritins are similar, in terms of their primary sequence, with the vertebrate H-type.<ref name=Andrews1992/> In ''E. coli'', a 20% similarity to human H-ferritin is observed.<ref name=Andrews1992/> Some ferritin complexes in vertebrates are [[hetero-oligomer]]s of two highly related [[gene]] products with slightly different [[physiological]] properties. The ratio of the two [[Homology (biology)|homologous]] proteins in the complex depends on the relative expression levels of the two genes.

''Cytosolic ferritin'' shell (apoferritin) is a heteropolymer of 24 subunits of heavy (H) and light (L) peptides that form a hollow spherical nanocage that covers an iron core composed of [[crystallite]]s together with [[phosphate]] and [[hydroxide]] ions. The resulting particle is similar to [[ferrihydrite]] (5Fe<sub>2</sub>O<sub>3</sub>·9H<sub>2</sub>O). Each ferritin complex can store about 4500 iron (Fe<sup>3+</sup>) ions.<ref name=Theil1987/><ref name="Andrews1992">{{cite journal | vauthors = Andrews SC, Arosio P, Bottke W, Briat JF, von Darl M, Harrison PM, Laulhère JP, Levi S, Lobreaux S, Yewdall SJ | title = Structure, function, and evolution of ferritins | journal = Journal of Inorganic Biochemistry | volume = 47 | issue = 3–4 | pages = 161–174 | year = 1992 | pmid = 1431878 | doi = 10.1016/0162-0134(92)84062-R }}</ref> The proportion of H to L subunits varies in ferritin from different tissues, explaining its heterogeneity on isoelectric focusing. L-rich ferritins (from spleen and liver) are more basic than H-rich ferritins (from heart and red blood cells).

''Serum ferritin'', which is typically iron-poor, consists almost exclusively of L subunits. Serum ferritin is heterogeneous due to glycosylation. The glycosylation and direct relationship of serum ferritin concentration to iron storage in macrophages suggest it is secreted by macrophages in response to changing iron levels.

''Human [[mitochondrial ferritin]]'', MtF, was found to express as a [[protein precursor|pro-protein]].<ref name="pmid11323407">{{cite journal | vauthors = Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J | title = A human mitochondrial ferritin encoded by an intronless gene | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 24437–24440 | date = July 2001 | pmid = 11323407 | doi = 10.1074/jbc.C100141200 | doi-access = free }}</ref> When a mitochondrion takes it up, it processes it into a mature protein similar to the ferritins found in the [[cytoplasm]], which it assembles to form functional ferritin shells. Unlike other human ferritins, it is a homopolymer of H type ferritin  and appears to have no introns (intronless) in its genetic code. The mitochondrial ferritin's [[Ramachandran plot]]<ref name="pmid12557186">{{cite journal | vauthors = Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC | title = Structure validation by Calpha geometry: phi,psi and Cbeta deviation | journal = Proteins | volume = 50 | issue = 3 | pages = 437–450 | date = February 2003 | pmid = 12557186 | doi = 10.1002/prot.10286 | url = http://www.rcsb.org/pdb/images/1R03_ram_m_500.pdf | quote = MolProbity Ramachandran analysis | s2cid = 8358424 | archive-url = https://web.archive.org/web/20121012105157/http://www.rcsb.org/pdb/images/1R03_ram_m_500.pdf | archive-date = 12 October 2012 }}</ref> shows its structure to be mainly [[alpha helix|alpha helical]] with a low prevalence of [[beta sheet]]s. It accumulates in large amounts in the erythroblasts of subjects with impaired heme synthesis.

== Function ==

=== Iron storage ===
[[File:Ferritin 3foldchannel.png|thumb|Iron uptake through the 3-fold channel of ferritin]]
Ferritin is present in every cell type.<ref name=Theil1987/> It serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required.<ref>{{Cite journal |vauthors=Seckback J |year=1982 |title=Ferreting out the secrets of plant ferritin - A review |journal=Journal of Plant Nutrition |volume=5 |issue=4–7 |pages=369–394 |doi=10.1080/01904168209362966|bibcode=1982JPlaN...5..369S }}</ref> The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of [[messenger RNA]] (mRNA), but also by changes in how the mRNA is stored and how efficiently it is transcribed.<ref name="Theil1987">{{cite journal | vauthors = Theil EC | title = Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms | journal = Annual Review of Biochemistry | volume = 56 | issue = 1 | pages = 289–315 | year = 1987 | pmid = 3304136 | doi = 10.1146/annurev.bi.56.070187.001445 }}</ref> One major trigger for the production of many ferritins is the mere presence of iron;<ref name=Theil1987/> an exception is the yolk ferritin of ''Lymnaea sp.'', which lacks an iron-responsive unit.<ref name=Andrews1992/>

Free iron is [[toxic]] to [[Cell (biology)|cells]] as it acts as a [[catalyst]] in the formation of [[free radical]]s from [[reactive oxygen species]] via the [[Fenton reaction]].<ref>{{cite journal | vauthors = Orino K, Lehman L, Tsuji Y, Ayaki H, Torti SV, Torti FM | title = Ferritin and the response to oxidative stress | journal = The Biochemical Journal | volume = 357 | issue = Pt 1 | pages = 241–247 | date = July 2001 | pmid = 11415455 | pmc = 1221947 | doi = 10.1042/0264-6021:3570241 }}</ref> Hence vertebrates have an elaborate set of protective mechanisms to bind iron in various [[Biological tissue|tissue]] compartments{{discuss}}. Within cells, iron is stored in a protein complex as ferritin or the related complex [[hemosiderin]]. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the [[reticuloendothelial system]], protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells, although hemosiderin is less readily available. Under [[steady state|steady-state]] conditions, the level of ferritin in the [[blood serum]] correlates with total body stores of iron; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.{{citation needed|date=July 2020}}

Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as [[mollusc]]s to control the concentration and distribution of iron, thus sculpting shell morphology and colouration.<ref name="Jackson2007">{{cite journal | vauthors = Jackson DJ, Wörheide G, Degnan BM | title = Dynamic expression of ancient and novel molluscan shell genes during ecological transitions | journal = BMC Evolutionary Biology | volume = 7 | issue = 1 | article-number = 160 | date = September 2007 | pmid = 17845714 | pmc = 2034539 | doi = 10.1186/1471-2148-7-160 | doi-access = free | bibcode = 2007BMCEE...7..160J }}</ref><ref>{{cite journal | vauthors = Yano M, Nagai K, Morimoto K, Miyamoto H | title = Shematrin: a family of glycine-rich structural proteins in the shell of the pearl oyster Pinctada fucata | journal = Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology | volume = 144 | issue = 2 | pages = 254–262 | date = June 2006 | pmid = 16626988 | doi = 10.1016/j.cbpb.2006.03.004 }}</ref> It also plays a role in the [[haemolymph]] of the [[polyplacophora]], where it serves to rapidly transport iron to the mineralizing [[radula]].<ref>{{Cite journal |vauthors=Kyung-Suk K, Webb J, Macey D |year=1986 |title=Properties and role of ferritin in the hemolymph of the chiton Clavarizona hirtosa |journal=Biochimica et Biophysica Acta (BBA) - General Subjects |volume=884 |issue=3 |pages=387–394 |doi=10.1016/0304-4165(86)90188-1}}</ref>

Iron is released from ferritin for use by ferritin degradation, which is performed mainly by [[lysosome]]s.<ref name="pmid20406137">{{cite journal | vauthors = Zhang Y, Mikhael M, Xu D, Li Y, Soe-Lin S, Ning B, Li W, Nie G, Zhao Y, Ponka P | title = Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit | journal = Antioxidants & Redox Signaling | volume = 13 | issue = 7 | pages = 999–1009 | date = October 2010 | pmid = 20406137 | doi = 10.1089/ars.2010.3129 }}</ref>

=== Ferroxidase activity ===

Vertebrate ferritin consists of two or three subunits which are named based on their molecular weight: L "light", H "heavy", and M "middle" subunits. The M subunit has only been reported in bullfrogs. In bacteria and archaea, ferritin consists of one subunit type.<ref name="ReferenceA">{{cite journal | vauthors = Honarmand Ebrahimi K, Hagedoorn PL, Hagen WR | title = Unity in the biochemistry of the iron-storage proteins ferritin and bacterioferritin | journal = Chemical Reviews | volume = 115 | issue = 1 | pages = 295–326 | date = January 2015 | pmid = 25418839 | doi = 10.1021/cr5004908 | doi-access = free }}</ref> H and M subunits of eukaryotic ferritin and all subunits of bacterial and archaeal ferritin are H-type and have ferroxidase activity, which means they are able to convert iron from the ferrous (Fe<sup>2+</sup>) to ferric (Fe<sup>3+</sup>) forms. This limits the deleterious reaction which occurs between ferrous iron and [[hydrogen peroxide]] known as the Fenton reaction which produces the highly damaging [[hydroxyl radical]]. The ferroxidase activity occurs at a diiron binding site in the middle of each H-type subunits.<ref name="ReferenceA" /><ref name="ReferenceB">{{cite journal | vauthors = Honarmand Ebrahimi K, Bill E, Hagedoorn PL, Hagen WR | title = The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement | journal = Nature Chemical Biology | volume = 8 | issue = 11 | pages = 941–948 | date = November 2012 | pmid = 23001032 | doi = 10.1038/nchembio.1071 }}</ref> After oxidation of Fe(II), the Fe(III) product stays metastably in the ferroxidase center and is displaced by Fe(II),<ref name="ReferenceB"/><ref>{{cite journal | vauthors = Watt RK | title = A unified model for ferritin iron loading by the catalytic center: implications for controlling "free iron" during oxidative stress | journal = ChemBioChem | volume = 14 | issue = 4 | pages = 415–419 | date = March 2013 | pmid = 23404831 | doi = 10.1002/cbic.201200783 | s2cid = 41485685 }}</ref> a mechanism that appears to be common among ferritins of all three domains of life.<ref name="ReferenceA"/> The light chain of ferritin has no ferroxidase activity but may be responsible for the electron transfer across the protein cage.<ref
name="pmid25348725">{{cite journal | vauthors = Carmona U, Li L, Zhang L, Knez M | title = Ferritin light-chain subunits: key elements for the electron transfer across the protein cage | journal = Chemical Communications | volume = 50 | issue = 97 | pages = 15358–15361 | date = December 2014 | pmid = 25348725 | doi = 10.1039/c4cc07996e }}</ref>

===Immune response===

Ferritin concentrations increase drastically in the presence of an infection or cancer. [[Endotoxins]] are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as ''Pseudomonas'', although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism.<ref name=Ong2005>{{cite journal | vauthors = Ong DS, Wang L, Zhu Y, Ho B, Ding JL | title = The response of ferritin to LPS and acute phase of Pseudomonas infection | journal = Journal of Endotoxin Research | volume = 11 | issue = 5 | pages = 267–280 | year = 2005 | pmid = 16262999 | doi = 10.1179/096805105X58698 }}</ref>

=== Stress response ===

The concentration of ferritin has been shown to increase in response to stresses such as [[Hypoxia (medical)|anoxia]],<ref>{{cite journal | vauthors = Larade K, Storey KB | title = Accumulation and translation of ferritin heavy chain transcripts following anoxia exposure in a marine invertebrate | journal = The Journal of Experimental Biology | volume = 207 | issue = Pt 8 | pages = 1353–1360 | date = March 2004 | pmid = 15010486 | doi = 10.1242/jeb.00872 | doi-access = free | bibcode = 2004JExpB.207.1353L }}</ref> which implies that it is an [[acute phase protein]].<ref>{{cite journal | vauthors = Beck G, Ellis TW, Habicht GS, Schluter SF, Marchalonis JJ | title = Evolution of the acute phase response: iron release by echinoderm (Asterias forbesi) coelomocytes, and cloning of an echinoderm ferritin molecule | journal = Developmental and Comparative Immunology | volume = 26 | issue = 1 | pages = 11–26 | date = January 2002 | pmid = 11687259 | doi = 10.1016/S0145-305X(01)00051-9 }}</ref>

=== Mitochondria ===

[[Mitochondrial ferritin]] has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.{{citation needed|date=July 2020}}

=== Yolk ===

In some snails, the protein component of the egg yolk is primarily ferritin.<ref name=Bottke1988>{{cite journal | vauthors = Bottke W, Burschyk M, Volmer J | title = On the origin of the yolk protein ferritin in snails | journal = Roux's Archives of Developmental Biology | volume = 197 | issue = 7 | pages = 377–382 | date = December 1988 | pmid = 28305744 | doi = 10.1007/BF00398988 | s2cid = 34033340 }}</ref> This is a different ferritin, with a different genetic sequence, from the somatic ferritin.  It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs.<ref name=Bottke1988/>

== Tissue distribution ==

In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma.<ref name=Ong2005/>

== Diagnostic uses ==

[[blood plasma|Serum]] ferritin levels are measured in [[medical laboratory|medical laboratories]] as part of the iron studies workup for [[iron-deficiency anemia]].<ref name=Theil2012/> They are measured in nanograms per milliliter (ng/mL) or micrograms per liter (μg/L); the two units are equivalent.

The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of [[anemia of chronic disease]], where ferritin is elevated in its capacity as an inflammatory [[acute phase protein]] and not as a marker for iron overload.{{citation needed|date=November 2021}}

=== Normal ranges ===
A normal ferritin blood level, referred to as the [[reference interval]] is determined by many [[Medical laboratory|testing laboratories]]. The ranges for ferritin can vary between laboratories but typical ranges would be between 40 and 300&nbsp;ng/mL (=μg/L) for males, and 20–200&nbsp;ng/mL (=μg/L) for females.<ref name="NEJM_Camaschella2015" />
{| class="wikitable"
|+ Normal ferritin blood levels according to sex and age{{Citation needed|date=February 2023}}
|-
| '''Adult males''' || 40–300&nbsp;ng/mL (μg/L)<ref name="NEJM_Camaschella2015" />
|-
| '''Adult females''' || 20–200&nbsp;ng/mL (μg/L)<ref name="NEJM_Camaschella2015" />
|-
| '''Children''' (6 months to 15 years) || 50–140&nbsp;ng/mL (μg/L)
|-
| '''Infants''' (1 to 5 months) || 50–200&nbsp;ng/mL (μg/L)
|-
| '''Neonates''' || 25–200&nbsp;ng/mL (μg/L)
|}

=== Deficiency ===
According to a 2014 review in the ''New England Journal of Medicine'' stated that a ferritin level below 30&nbsp;ng/mL indicates [[iron deficiency]], while a level below 10&nbsp;ng/mL indicates iron-deficiency anemia.<ref name="NEJM_Camaschella2015">{{cite journal | vauthors = Camaschella C | title = Iron-deficiency anemia | journal = The New England Journal of Medicine | volume = 372 | issue = 19 | pages = 1832–1843 | date = May 2015 | pmid = 25946282 | doi = 10.1056/NEJMra1401038 | s2cid = 17628280 | veditors = Longo DL }}</ref> A 2020 World Health Organization guideline states that ferritin indicates iron deficiency below 12&nbsp;ng/mL in apparently-healthy children under 5 and 15&nbsp;ng/mL in apparently-healthy individuals of 5 and over.<ref>{{Cite book | publisher = World Health Organization |title=WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. |date=2020 |isbn=978-92-4-000012-4 |location=Geneva, Switzerland |oclc=1265083396}}</ref>

Some studies suggest that women with [[fatigue]] and ferritin below 50&nbsp;ng/mL see reduced fatigue after iron supplementation.<ref>{{cite journal | vauthors = Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pécoud A, Favrat B | title = Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial | journal = BMJ | volume = 326 | issue = 7399 | pages = 1124–0 | date = May 2003 | pmid = 12763985 | pmc = 156009 | doi = 10.1136/bmj.326.7399.1124 }}</ref><ref>{{cite journal | vauthors = Vaucher P, Druais PL, Waldvogel S, Favrat B | title = Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial | journal = CMAJ | volume = 184 | issue = 11 | pages = 1247–1254 | date = August 2012 | pmid = 22777991 | pmc = 3414597 | doi = 10.1503/cmaj.110950 }}</ref>

In the setting of anemia, low serum ferritin is the most specific lab finding for [[iron-deficiency anemia]].<ref>{{cite journal | vauthors = Guyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R | title = Diagnosis of iron-deficiency anemia in the elderly | journal = The American Journal of Medicine | volume = 88 | issue = 3 | pages = 205–209 | date = March 1990 | pmid = 2178409 | doi = 10.1016/0002-9343(90)90143-2 }}</ref> However it is less sensitive, since its levels are increased in the blood by infection or any type of chronic inflammation,<ref name=Firkin1997>{{cite journal | url = http://www.australianprescriber.com/magazine/20/3/74/6 | title = Interpretation of biochemical tests for iron deficiency: diagnostic difficulties related to limitations of individual tests | archive-url = https://web.archive.org/web/20120325192442/http://www.australianprescriber.com/magazine/20/3/74/6/ | archive-date=2012-03-25 | vauthors = Firkin F, Rush B | journal = Australian Prescriber | date = 1997 | volume = 20 | pages = 74–6 | doi = 10.18773/austprescr.1997.063 | url-status = usurped | doi-access = free }}</ref> and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range. A ''falsely low'' blood ferritin (equivalent to a [[false positive]] test) is very uncommon,<ref name="Firkin1997" /> but can result from a [[hook effect]] of the measuring tools in extreme cases.<ref>{{cite book |url=https://books.google.com/books?id=9VBFVkMX3N0C&pg=PA236 |title=The Science of Laboratory Diagnosis |vauthors=Burnett D, Crocker JR |publisher=ISIS Medical Media |year=1999 |isbn=978-1-899066-62-9 |page=341}}</ref>

Low ferritin may also indicate [[hypothyroidism]],<ref>{{cite journal | vauthors = R V, Dhiman P, Kollipaka R, P S, V H | title = Association of Hypothyroidism With Low Serum Ferritin Levels and Iron-Deficiency Anemia During the First Trimester of Pregnancy | journal = Cureus | volume = 14 | issue = 8 | article-number = e28307 | date = August 2022 | pmid = 36158423 | pmc = 9498961 | doi = 10.7759/cureus.28307 | doi-access = free }}</ref> [[Scurvy|vitamin C deficiency]] or [[celiac disease]].{{citation needed|date=April 2022}}

Low serum ferritin levels are seen in some patients with [[restless legs syndrome]], not necessarily related to anemia, but perhaps due to low iron stores short of anemia.<ref name="sleepmed3">{{cite journal | vauthors = Kryger MH, Otake K, Foerster J | title = Low body stores of iron and restless legs syndrome: a correctable cause of insomnia in adolescents and teenagers | journal = Sleep Medicine | volume = 3 | issue = 2 | pages = 127–132 | date = March 2002 | pmid = 14592231 | doi = 10.1016/S1389-9457(01)00160-5 }}
</ref><ref>{{cite journal | vauthors = Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J | title = CSF iron, ferritin and transferrin levels in restless legs syndrome | journal = Journal of Sleep Research | volume = 14 | issue = 1 | pages = 43–47 | date = March 2005 | pmid = 15743333 | doi = 10.1111/j.1365-2869.2004.00403.x | s2cid = 12959227 | doi-access = free }}</ref>

[[Vegetarianism]] is not a cause of low serum ferritin levels, according to the American Dietetic Association's position in 2009: "Incidence of iron-deficiency anemia among vegetarians is similar to that of non-vegetarians. Although vegetarian adults have lower iron stores than non-vegetarians, their serum ferritin levels are usually within the normal range."<ref>{{cite journal | vauthors = Craig WJ, Mangels AR | title = Position of the American Dietetic Association: vegetarian diets | journal = Journal of the American Dietetic Association | volume = 109 | issue = 7 | pages = 1266–1282 | date = July 2009 | pmid = 19562864 | doi = 10.1016/j.jada.2009.05.027 | s2cid = 7906168 }}</ref>

=== Excess ===

If  ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload.

Ferritin is also used as a [[Biomarker|marker]] for [[Iron overload|iron overload disorder]]s, such as [[hemochromatosis]] or [[hemosiderosis]]. [[Adult-onset Still's disease]], some [[porphyrias]], and [[hemophagocytic lymphohistiocytosis]]/[[macrophage activation syndrome]] are diseases in which the ferritin level may be abnormally raised.

As ferritin is also an [[acute phase proteins|acute-phase reactant]], it is often elevated in the course of disease. A normal [[C-reactive protein]] can be used to exclude elevated ferritin caused by acute phase reactions. {{Citation needed|date=October 2017}}

Ferritin has been shown to be elevated in some cases of [[COVID-19]] and may correlate with worse clinical outcome.<ref>{{cite journal | vauthors = Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q | title = Clinical and immunological features of severe and moderate coronavirus disease 2019 | journal = The Journal of Clinical Investigation | volume = 130 | issue = 5 | pages = 2620–2629 | date = May 2020 | pmid = 32217835 | pmc = 7190990 | doi = 10.1172/JCI137244 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zachariah M, Maamoun H, Milano L, Rayman MP, Meira LB, Agouni A | title = Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium | journal = Journal of Cellular Physiology | volume = 236 | issue = 6 | pages = 4348–4359 | date = June 2021 | pmc = 8108185 | doi = 10.1080/20905068.2020.1870788 | doi-access = free | pmid = 33241572 }}</ref> Ferritin and [[Interleukin 6|IL-6]] are considered to be possible immunological biomarkers for severe and fatal cases of COVID-19. Ferritin and C-reactive protein may be possible screening tools for early diagnosis of [[systemic inflammatory response syndrome]] in cases of COVID-19.<ref name="Melo">{{cite journal | vauthors = Melo AK, Milby KM, Caparroz AL, Pinto AC, Santos RR, Rocha AP, Ferreira GA, Souza VA, Valadares LD, Vieira RM, Pileggi GS, Trevisani VF | title = Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis | journal = PLOS ONE | volume = 16 | issue = 6 | article-number = e0253894 | date = 29 June 2021 | pmid = 34185801 | pmc = 8241122 | doi = 10.1371/journal.pone.0253894 | doi-access = free | bibcode = 2021PLoSO..1653894M }}</ref><ref name="Dance">{{cite news | vauthors = Dance A | date= 10 April 2020 |title=What is a cytokine storm? |url=https://knowablemagazine.org/article/health-disease/2020/what-cytokine-storm |website=Knowable Magazine |publisher=Annual Reviews |access-date=9 August 2021}}</ref>

According to a study of [[anorexia nervosa]] patients, ferritin can be elevated during periods of acute [[malnutrition|malnourishment]], perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls.<ref>{{cite journal | vauthors = Kennedy A, Kohn M, Lammi A, Clarke S | title = Iron status and haematological changes in adolescent female inpatients with anorexia nervosa | journal = Journal of Paediatrics and Child Health | volume = 40 | issue = 8 | pages = 430–432 | date = August 2004 | pmid = 15265182 | doi = 10.1111/j.1440-1754.2004.00432.x | s2cid = 26269832 }}</ref>

Another study suggests that due to the catabolic nature of anorexia nervosa, isoferritins may be released. Furthermore, ferritin has significant non-storage roles within the body, such as protection from [[oxidative damage]]. The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through [[immunoassay]] or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status.<ref>{{cite journal | vauthors = Tran J, Story C, Moore D, Metz M | title = Unexpected increased ferritin concentration in patients with anorexia nervosa | journal = Annals of Clinical Biochemistry | volume = 50 | issue = Pt 5 | pages = 504–506 | date = September 2013 | pmid = 23897102 | doi = 10.1177/0004563213490289 | s2cid = 9927714 | doi-access = free }}</ref>

Studies reveal that a transferrin saturation (serum iron concentration ÷ total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism ([[hereditary hemochromatosis]], heterozygotes, and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of hereditary hemochromatosis, especially while serum ferritin still remains low. The retained iron in hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relative low in hereditary hemochromatosis, while transferrin saturation is high.<ref name="pmid21452290">{{cite journal | vauthors = Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS | title = Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases | journal = Hepatology | volume = 54 | issue = 1 | pages = 328–343 | date = July 2011 | pmid = 21452290 | pmc = 3149125 | doi = 10.1002/hep.24330 }}</ref><ref>{{cite web | title = Hemochromatosis | url = http://eguideline.guidelinecentral.com/i/98549-aasld-hemochromatosis/2 | work = guidelinecentral.com }}</ref>

=== In chronic liver diseases ===
Hematological abnormalities often associate with chronic liver diseases. Both iron overload and iron deficient anemia have been reported in patients with liver cirrhosis.<ref>{{cite journal | vauthors = Cotler SJ, Bronner MP, Press RD, Carlson TH, Perkins JD, Emond MJ, Kowdley KV | title = End-stage liver disease without hemochromatosis associated with elevated hepatic iron index | language = English | journal = Journal of Hepatology | volume = 29 | issue = 2 | pages = 257–262 | date = August 1998 | pmid = 9722207 | doi = 10.1016/S0168-8278(98)80011-1 }}</ref><ref>{{cite journal | vauthors = Gkamprela E, Deutsch M, Pectasides D | title = Iron deficiency anemia in chronic liver disease: etiopathogenesis, diagnosis and treatment | journal = Annals of Gastroenterology | volume = 30 | issue = 4 | pages = 405–413 | date = 2017 | pmid = 28655976 | pmc = 5479992 | doi = 10.20524/aog.2017.0152 | doi-access = free }}</ref> The former is mainly due to reduced [[hepcidin]] level caused by the decreased synthetic capacity of the liver, while the latter is due to acute and chronic bleeding caused by [[portal hypertension]]. Inflammation is also present in patients with advanced chronic liver disease. As a consequence, elevated hepatic and serum ferritin levels are consistently reported in chronic liver diseases.<ref>{{cite journal | vauthors = Guyader D, Thirouard AS, Erdtmann L, Rakba N, Jacquelinet S, Danielou H, Perrin M, Jouanolle AM, Brissot P, Deugnier Y | title = Liver iron is a surrogate marker of severe fibrosis in chronic hepatitis C | journal = Journal of Hepatology | volume = 46 | issue = 4 | pages = 587–595 | date = April 2007 | pmid = 17156889 | doi = 10.1016/j.jhep.2006.09.021 }}</ref><ref>{{cite journal | vauthors = Adams PC | title = Iron overload in viral and alcoholic liver disease | journal = Journal of Hepatology | volume = 28 | issue = Suppl 1 | pages = 19–20 | date = 1998 | pmid = 9575444 | doi = 10.1016/S0168-8278(98)80370-X }}</ref><ref>{{cite journal | vauthors = Eng SC, Taylor SL, Reyes V, Raaka S, Berger J, Kowdley KV | title = Hepatic iron overload in alcoholic end-stage liver disease is associated with iron deposition in other organs in the absence of HFE-1 hemochromatosis | journal = Liver International | volume = 25 | issue = 3 | pages = 513–517 | date = June 2005 | pmid = 15910487 | doi = 10.1111/j.1478-3231.2005.01004.x | s2cid = 23125116 }}</ref>

Studies showed association between high serum ferritin levels and increased risk of short-term mortality in cirrhotic patients with acute decompensation<ref>{{cite journal | vauthors = Maiwall R, Kumar S, Chaudhary AK, Maras J, Wani Z, Kumar C, Rastogi A, Bihari C, Vashisht C, Sarin SK | title = Serum ferritin predicts early mortality in patients with decompensated cirrhosis | journal = Journal of Hepatology | volume = 61 | issue = 1 | pages = 43–50 | date = July 2014 | pmid = 24681346 | doi = 10.1016/j.jhep.2014.03.027 }}</ref> and acute-on-chronic liver failure.<ref>{{cite journal | vauthors = Maras JS, Maiwall R, Harsha HC, Das S, Hussain MS, Kumar C, Bihari C, Rastogi A, Kumar M, Trehanpati N, Sharma S, Pandey A, Sarin SK | title = Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute-on-chronic liver failure | journal = Hepatology | volume = 61 | issue = 4 | pages = 1306–1320 | date = April 2015 | pmid = 25475192 | doi = 10.1002/hep.27636 | doi-access = free }}</ref> An other study found association between high serum ferritin levels and increased risk of long-term mortality in compensated and stable decompensated cirrhotic patients.<ref name=":0">{{cite journal | vauthors = Tornai D, Antal-Szalmas P, Tornai T, Papp M, Tornai I, Sipeki N, Janka T, Balogh B, Vitalis Z | title = Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients: a cohort study | journal = BMC Gastroenterology | volume = 21 | issue = 1 | article-number = 94 | date = March 2021 | pmid = 33653274 | pmc = 7923668 | doi = 10.1186/s12876-021-01669-w | doi-access = free }}</ref> The same study demonstrated that increased serum ferritin levels could predict the development of bacterial infection in stable decompensated cirrhotic patients, while in compensated cirrhotic patients the appearance of the very first acute decompensation episode showed higher incidence in patients with low serum ferritin levels. This latter finding was explained by the association between chronic bleeding and increased portal pressure.<ref name=":0" />

== Discovery ==
Ferritin was discovered in 1937 by the [[Czechoslovakia]]n scientist {{ill|Vilém Laufberger|cs}}.<ref>{{cite journal | vauthors = Laufberger V |title=Sur la Cristallisation de la Ferritine |journal=Bulletin de la Société de Chimie Biologique |date=1937 |volume=19 |pages=1575–1582 | issn=0037-9042}}</ref><ref name = "Kresge_2004"  />{{rp|e9}} [[Sam Granick]] and [[Leonor Michaelis]] produced apoferritin in 1942<ref name = "Kresge_2004"  />{{rp|e10}}

== Applications ==

Ferritin is used in [[materials science]] as a precursor in making iron [[nanoparticle]]s (NP) for [[carbon nanotube]] growth by [[chemical vapor deposition]].  It has also been shown to effectively store electrons for hours and <ref>{{Cite journal |last1=Wolszczak |first1=Marian |last2=Gajda |first2=Joanna |date=2010-08-17 |title=Iron release from ferritin induced by light and ionizing radiation |journal=Research on Chemical Intermediates |volume=36 |issue=5 |pages=549–563 |doi=10.1007/s11164-010-0155-0 |issn=0922-6168|doi-access=free }}</ref> to facilitate electron tunneling under ambient conditions,<ref>{{Cite journal |last1=Kumar |first1=Karuppannan Senthil |last2=Pasula |first2=Rupali Reddy |last3=Lim |first3=Sierin |last4=Nijhuis |first4=Christian A. |date=2015-12-28 |title=Long-Range Tunneling Processes across Ferritin-Based Junctions |journal=Advanced Materials |volume=28 |issue=9 |pages=1824–1830 |doi=10.1002/adma.201504402 |pmid=26708136 |issn=0935-9648}}</ref> properties that may be involved in biological processes.<ref>{{Cite journal |last1=Perez |first1=Ismael Diez |last2=Lim |first2=Sierin |last3=Nijhuis |first3=Christian A. |last4=Pluchery |first4=Olivier |last5=Rourk |first5=Christopher J. |date=June 2023 |title=Electron Tunneling in Ferritin and Associated Biosystems |journal=IEEE Transactions on Molecular, Biological and Multi-Scale Communications |volume=9 |issue=2 |pages=263–272 |doi=10.1109/tmbmc.2023.3275793 |bibcode=2023ITMBM...9..263P |issn=2372-2061|hdl=10356/174271 |hdl-access=free }}</ref>

Cavities formed by ferritin and mini-ferritins ([[Dps (DNA-binding proteins from starved cells)|Dps]]) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles.<ref>{{cite journal | vauthors = Kasyutich O, Ilari A, Fiorillo A, Tatchev D, Hoell A, Ceci P | title = Silver ion incorporation and nanoparticle formation inside the cavity of Pyrococcus furiosus ferritin: structural and size-distribution analyses | journal = Journal of the American Chemical Society | volume = 132 | issue = 10 | pages = 3621–3627 | date = March 2010 | pmid = 20170158 | doi = 10.1021/ja910918b | bibcode = 2010JAChS.132.3621K }}</ref><ref>{{cite journal | vauthors = Uchida M, Flenniken ML, Allen M, Willits DA, Crowley BE, Brumfield S, Willis AF, Jackiw L, Jutila M, Young MJ, Douglas T | title = Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles | journal = Journal of the American Chemical Society | volume = 128 | issue = 51 | pages = 16626–16633 | date = December 2006 | pmid = 17177411 | doi = 10.1021/ja0655690 | bibcode = 2006JAChS.12816626U }}</ref><ref>{{cite journal | vauthors = Li M, Viravaidya C, Mann S | title = Polymer-mediated synthesis of ferritin-encapsulated inorganic nanoparticles | journal = Small | volume = 3 | issue = 9 | pages = 1477–1481 | date = September 2007 | pmid = 17768776 | doi = 10.1002/smll.200700199 }}</ref><ref>{{cite journal | vauthors = Ueno T, Suzuki M, Goto T, Matsumoto T, Nagayama K, Watanabe Y | title = Size-selective olefin hydrogenation by a Pd nanocluster provided in an apo-ferritin cage | journal = Angewandte Chemie | volume = 43 | issue = 19 | pages = 2527–2530 | date = May 2004 | pmid = 15127443 | doi = 10.1002/anie.200353436 }}</ref> [[Protein]] shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications.<ref name="Theil2012" /><ref>[https://scitechdaily.com/stanfords-single-dose-nanoparticle-vaccine-for-covid-19/ Stanford's Single-Dose Nanoparticle Vaccine for COVID-19]. On: SciTechDaily. January 10, 2021. Source: Stanford University</ref>

Experimental COVID-19 vaccines have been produced that display the [[coronavirus spike protein|spike protein]]'s receptor binding domain on the surface of ferritin nanoparticles.<ref>{{cite journal | vauthors = Wang W, Huang B, Zhu Y, Tan W, Zhu M | title = Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice | journal = Cellular & Molecular Immunology | volume = 18 | issue = 3 | pages = 749–751 | date = March 2021 | pmid = 33580169 | pmc = 7880661 | doi = 10.1038/s41423-021-00643-6 }}</ref>

Apoferritin is also the most commonly-used protein to test resolution in Cryogenic Electron Microscopy (Cryo-EM) single particle analysis, due to its highly symmetrical shape and ease of sample preparation.<ref>{{Cite journal |last1=Premageetha |first1=Gowtham ThambraRajan |last2=Vinothkumar |first2=Kutti R. |last3=Bose |first3=Sucharita |date=2024-04-01 |title=Exploring advances in single particle CryoEM with apoferritin: From blobs to true atomic resolution |url=https://www.sciencedirect.com/science/article/pii/S135727252400027X |journal=The International Journal of Biochemistry & Cell Biology |volume=169 |article-number=106536 |doi=10.1016/j.biocel.2024.106536 |pmid=38307321 |issn=1357-2725|url-access=subscription }}</ref><ref>{{Citation |last1=Diebolder |first1=Christoph A. |title=From Tube to Structure: SPA Cryo-EM Workflow Using Apoferritin as an Example |date=2021 |work=Structural Proteomics: High-Throughput Methods |pages=229–256 |editor-last=Owens |editor-first=Raymond J. |place=New York, NY |publisher=Springer US |language=en |doi=10.1007/978-1-0716-1406-8_12 |isbn=978-1-0716-1406-8 |last2=Dillard |first2=Rebecca S. |last3=Renault |first3=Ludovic |pmid=33950393 }}</ref> Apoferritin holds the current record for the highest resolution structure determined by cryo-EM at around 1.1-1.2 Å.<ref>{{Cite journal |last1=Nakane |first1=Takanori |last2=Kotecha |first2=Abhay |last3=Sente |first3=Andrija |last4=McMullan |first4=Greg |last5=Masiulis |first5=Simonas |last6=Brown |first6=Patricia M. G. E. |last7=Grigoras |first7=Ioana T. |last8=Malinauskaite |first8=Lina |last9=Malinauskas |first9=Tomas |last10=Miehling |first10=Jonas |last11=Uchański |first11=Tomasz |last12=Yu |first12=Lingbo |last13=Karia |first13=Dimple |last14=Pechnikova |first14=Evgeniya V. |last15=de Jong |first15=Erwin |date=November 2020 |title=Single-particle cryo-EM at atomic resolution |journal=Nature |language=en |volume=587 |issue=7832 |pages=152–156 |doi=10.1038/s41586-020-2829-0 |pmid=33087931 |pmc=7611073 |bibcode=2020Natur.587..152N |issn=1476-4687}}</ref><ref>{{Cite journal |last1=Yip |first1=Ka Man |last2=Fischer |first2=Niels |last3=Paknia |first3=Elham |last4=Chari |first4=Ashwin |last5=Stark |first5=Holger |date=November 2020 |title=Atomic-resolution protein structure determination by cryo-EM |url=https://www.nature.com/articles/s41586-020-2833-4 |journal=Nature |language=en |volume=587 |issue=7832 |pages=157–161 |doi=10.1038/s41586-020-2833-4 |pmid=33087927 |bibcode=2020Natur.587..157Y |issn=1476-4687|url-access=subscription }}</ref><ref>{{Cite journal |last1=Küçükoğlu |first1=Berk |last2=Mohammed |first2=Inayathulla |last3=Guerrero-Ferreira |first3=Ricardo C. |last4=Ribet |first4=Stephanie M. |last5=Varnavides |first5=Georgios |last6=Leidl |first6=Max Leo |last7=Lau |first7=Kelvin |last8=Nazarov |first8=Sergey |last9=Myasnikov |first9=Alexander |last10=Kube |first10=Massimo |last11=Radecke |first11=Julika |last12=Sachse |first12=Carsten |last13=Müller-Caspary |first13=Knut |last14=Ophus |first14=Colin |last15=Stahlberg |first15=Henning |date=2024-09-14 |title=Low-dose cryo-electron ptychography of proteins at sub-nanometer resolution |journal=Nature Communications |language=en |volume=15 |issue=1 |page=8062 |doi=10.1038/s41467-024-52403-5 |pmid=39277607 |pmc=11401879 |bibcode=2024NatCo..15.8062K |issn=2041-1723}}</ref>

== Notes ==
The primary peptide sequence of human ferritin is:<ref>{{cite web | url=https://www.uniprot.org/uniprot/Q8TD27 | title=Ferritin - Homo sapiens (Human) | work = UniProt | id = Q8TD27 }}</ref>
<syntaxhighlight lang="text">
MTTASTSQVR QNYHQDSEAA INRQINLELY ASYVYLSMSY YFDRDDVALK NFAKYFLHQS HEEREHAEKL MKLQNQRGGR IFLQDIKKPD CDDWESGLNA MECALHLEKN VNQSLLEFPS PISPSPSCWH HYTTNRPQPQ HHLLRPRRRK RPHSIPTPIL IFRSP.
</syntaxhighlight>

== See also ==
* [[Bacterioferritin]]
* [[DNA-binding protein from starved cells]]
* [[Ferritin light chain]]
* [[Transferrin]]

== References ==
{{reflist|30em}}

== External links ==
{{Wiktionary|ferritin|apoferritin}}
* {{MeshName|Ferritins}}
* [http://labtestsonline.org/understanding/analytes/ferritin/tab/test Ferritin] at Lab Tests Online
* {{PDBe-KB2|P02792|Ferritin light chain}}
* {{PDBe-KB2|P02794|Ferritin heavy chain}}
* {{PDBe-KB2|Q8N4E7|Ferritin, mitochondrial}}

{{Iron-binding proteins}}
{{Metal metabolism}}
{{Blood tests}}

[[Category:Iron metabolism]]
[[Category:Blood tests]]
[[Category:Chemical pathology]]
[[Category:Acute-phase proteins]]
[[Category:Storage proteins]]