Full text data of FTH1
FTH1
(FTH, FTHL6)
[Confidence: low (only semi-automatic identification from reviews)]
Ferritin heavy chain; Ferritin H subunit; 1.16.3.1 (Cell proliferation-inducing gene 15 protein; Ferritin heavy chain, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ferritin heavy chain; Ferritin H subunit; 1.16.3.1 (Cell proliferation-inducing gene 15 protein; Ferritin heavy chain, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02794
ID FRIH_HUMAN Reviewed; 183 AA.
AC P02794; B3KNR5; Q3KRA8; Q3SWW1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Ferritin heavy chain;
DE Short=Ferritin H subunit;
DE EC=1.16.3.1;
DE AltName: Full=Cell proliferation-inducing gene 15 protein;
DE Contains:
DE RecName: Full=Ferritin heavy chain, N-terminally processed;
GN Name=FTH1; Synonyms=FTH, FTHL6; ORFNames=OK/SW-cl.84, PIG15;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hepatocyte;
RX PubMed=6323167;
RA Costanzo F., Santoro C., Colantuoni V., Bensi G., Raugei G.,
RA Romano V., Cortese R.;
RT "Cloning and sequencing of a full length cDNA coding for a human
RT apoferritin H chain: evidence for a multigene family.";
RL EMBO J. 3:23-27(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3840162;
RA Boyd D., Vecoli C., Belcher D.M., Jain S.K., Drysdale J.W.;
RT "Structural and functional relationships of human ferritin H and L
RT chains deduced from cDNA clones.";
RL J. Biol. Chem. 260:11755-11761(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3023856;
RA Chou C.-C., Gatti R.A., Fuller M.L., Concannon P., Wong A., Chada S.,
RA Davis R.C., Salser W.A.;
RT "Structure and expression of ferritin genes in a human promyelocytic
RT cell line that differentiates in vitro.";
RL Mol. Cell. Biol. 6:566-573(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3003694; DOI=10.1093/nar/14.2.721;
RA Costanzo F., Colombo M., Staempfli S., Santoro C., Marone M.,
RA Frank R., Delius H., Cortese R.;
RT "Structure of gene and pseudogenes of human apoferritin H.";
RL Nucleic Acids Res. 14:721-736(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3020541; DOI=10.1073/pnas.83.19.7226;
RA Hentze M.W., Keim S., Papadopoulos P., O'Brien S., Modi W.,
RA Drysdale J.W., Leonard W.J., Harford J.B., Klausner R.D.;
RT "Cloning, characterization, expression, and chromosomal localization
RT of a human ferritin heavy-chain gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7226-7230(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7916709; DOI=10.1016/0378-1119(93)90380-L;
RA Dhar M., Chauthaiwale V.M., Joshi J.G.;
RT "Sequence of a cDNA encoding the ferritin H-chain from an 11-week-old
RT human fetal brain.";
RL Gene 126:275-278(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Chauthaiwale V.M., Dhar M., McLachlan D.R., Joshi J.G.;
RT "Cloning of a novel full length cDNA for ferritin heavy chain from
RT normal adult human and Alzheimer's brain.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Franco A.V., Gray C.P., Myers K., Hersey P.;
RT "Detection of ferritin heavy chain by SEREX: a multifunctional
RT molecule in malignant tumour cells.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation gene 15.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Cervix, Colon, Lung, Ovary, Prostate, and
RC Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 128-183.
RX PubMed=6589621; DOI=10.1073/pnas.81.15.4751;
RA Boyd D., Jain S.K., Crampton J., Barrett K.J., Drysdale J.;
RT "Isolation and characterization of a cDNA clone for human ferritin
RT heavy chain.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4751-4755(1984).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179 AND SER-183, AND
RP MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=1992356; DOI=10.1038/349541a0;
RA Lawson D.M., Artymiuk P.J., Yewdall S.J., Smith J.M.A.,
RA Livingstone J.C., Treffry A., Luzzago A., Levi S., Arosio P.,
RA Cesarini G., Thomas C.D., Shaw W.V., Harrison P.M.;
RT "Solving the structure of human H ferritin by genetically engineering
RT intermolecular crystal contacts.";
RL Nature 349:541-544(1991).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=9159481; DOI=10.1006/jmbi.1997.0970;
RA Hempstead P.D., Yewdall S.J., Fernie A.R., Lawson D.M., Artymiuk P.J.,
RA Rice D.W., Ford G.C., Harrison P.M.;
RT "Comparison of the three-dimensional structures of recombinant human H
RT and horse L ferritins at high resolution.";
RL J. Mol. Biol. 268:424-448(1997).
CC -!- FUNCTION: Stores iron in a soluble, non-toxic, readily available
CC form. Important for iron homeostasis. Has ferroxidase activity.
CC Iron is taken up in the ferrous form and deposited as ferric
CC hydroxides after oxidation. Also plays a role in delivery of iron
CC to cells. Mediates iron uptake in capsule cells of the developing
CC kidney (By similarity).
CC -!- CATALYTIC ACTIVITY: 4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O.
CC -!- SUBUNIT: Oligomer of 24 subunits. There are two types of subunits:
CC L (light) chain and H (heavy) chain. The major chain can be light
CC or heavy, depending on the species and tissue type. The functional
CC molecule forms a roughly spherical shell with a diameter of 12 nm
CC and contains a central cavity into which the insoluble mineral
CC iron core is deposited.
CC -!- INTERACTION:
CC Q9UER7:DAXX; NbExp=5; IntAct=EBI-713259, EBI-77321;
CC P02792:FTL; NbExp=3; IntAct=EBI-713259, EBI-713279;
CC P61244:MAX; NbExp=2; IntAct=EBI-713259, EBI-751711;
CC -!- MISCELLANEOUS: In human liver the heavy chain is the major chain.
CC -!- SIMILARITY: Belongs to the ferritin family.
CC -!- SIMILARITY: Contains 1 ferritin-like diiron domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI05803.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ferritin entry;
CC URL="http://en.wikipedia.org/wiki/Ferritin";
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DR EMBL; X00318; CAA25086.1; -; mRNA.
DR EMBL; M11146; AAA52437.1; -; mRNA.
DR EMBL; M12937; AAA35830.1; -; mRNA.
DR EMBL; X03487; CAA27205.1; -; Genomic_DNA.
DR EMBL; X03488; CAA27205.1; JOINED; Genomic_DNA.
DR EMBL; M14212; AAA52438.1; -; Genomic_DNA.
DR EMBL; M14211; AAA52438.1; JOINED; Genomic_DNA.
DR EMBL; M97164; AAA35832.1; -; mRNA.
DR EMBL; L20941; AAA35833.1; -; mRNA.
DR EMBL; AF088851; AAF89523.1; -; mRNA.
DR EMBL; AY258285; AAP82230.1; -; mRNA.
DR EMBL; AB062402; BAB93489.1; -; mRNA.
DR EMBL; AK054816; BAG51427.1; -; mRNA.
DR EMBL; DQ496108; ABF47097.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW73989.1; -; Genomic_DNA.
DR EMBL; BC000857; AAH00857.1; -; mRNA.
DR EMBL; BC001399; AAH01399.1; -; mRNA.
DR EMBL; BC011359; AAH11359.1; -; mRNA.
DR EMBL; BC013724; AAH13724.1; -; mRNA.
DR EMBL; BC015156; AAH15156.1; -; mRNA.
DR EMBL; BC016009; AAH16009.1; -; mRNA.
DR EMBL; BC016857; AAH16857.1; -; mRNA.
DR EMBL; BC063514; AAH63514.1; -; mRNA.
DR EMBL; BC066961; AAH66961.1; -; mRNA.
DR EMBL; BC073750; AAH73750.1; -; mRNA.
DR EMBL; BC104643; AAI04644.1; -; mRNA.
DR EMBL; BC105802; AAI05803.1; ALT_INIT; mRNA.
DR EMBL; M15383; AAA52479.1; -; mRNA.
DR PIR; A23517; FRHUH.
DR RefSeq; NP_002023.2; NM_002032.2.
DR RefSeq; XP_005273922.1; XM_005273865.1.
DR UniGene; Hs.524910; -.
DR UniGene; Hs.645560; -.
DR PDB; 1FHA; X-ray; 2.40 A; A=1-183.
DR PDB; 2CEI; X-ray; 1.80 A; A=2-182.
DR PDB; 2CHI; X-ray; 1.60 A; A=2-182.
DR PDB; 2CIH; X-ray; 1.50 A; A=2-182.
DR PDB; 2CLU; X-ray; 2.10 A; A=2-182.
DR PDB; 2CN6; X-ray; 2.20 A; A=2-182.
DR PDB; 2CN7; X-ray; 1.75 A; A=2-182.
DR PDB; 2FHA; X-ray; 1.90 A; A=1-183.
DR PDB; 2IU2; X-ray; 1.80 A; A=2-182.
DR PDB; 2Z6M; X-ray; 2.72 A; A/B/C/D/E/F/G/H/I/J/K/L=2-177.
DR PDB; 3AJO; X-ray; 1.52 A; A=2-183.
DR PDB; 3AJP; X-ray; 1.90 A; A=2-183.
DR PDB; 3AJQ; X-ray; 1.58 A; A=2-183.
DR PDB; 3ERZ; X-ray; 3.06 A; A/B/C/D/E/F/G/H/I/J/K/L=1-183.
DR PDB; 3ES3; X-ray; 2.79 A; A=1-183.
DR PDB; 4DYX; X-ray; 1.85 A; A=6-177.
DR PDB; 4DYY; X-ray; 1.90 A; A=6-177.
DR PDB; 4DYZ; X-ray; 2.30 A; A=6-177.
DR PDB; 4DZ0; X-ray; 2.50 A; A=6-177.
DR PDBsum; 1FHA; -.
DR PDBsum; 2CEI; -.
DR PDBsum; 2CHI; -.
DR PDBsum; 2CIH; -.
DR PDBsum; 2CLU; -.
DR PDBsum; 2CN6; -.
DR PDBsum; 2CN7; -.
DR PDBsum; 2FHA; -.
DR PDBsum; 2IU2; -.
DR PDBsum; 2Z6M; -.
DR PDBsum; 3AJO; -.
DR PDBsum; 3AJP; -.
DR PDBsum; 3AJQ; -.
DR PDBsum; 3ERZ; -.
DR PDBsum; 3ES3; -.
DR PDBsum; 4DYX; -.
DR PDBsum; 4DYY; -.
DR PDBsum; 4DYZ; -.
DR PDBsum; 4DZ0; -.
DR ProteinModelPortal; P02794; -.
DR SMR; P02794; 6-177.
DR DIP; DIP-38301N; -.
DR IntAct; P02794; 28.
DR MINT; MINT-4822446; -.
DR STRING; 9606.ENSP00000273550; -.
DR DrugBank; DB00893; Iron Dextran.
DR PhosphoSite; P02794; -.
DR DMDM; 120516; -.
DR UCD-2DPAGE; P02794; -.
DR PaxDb; P02794; -.
DR PRIDE; P02794; -.
DR DNASU; 2495; -.
DR Ensembl; ENST00000273550; ENSP00000273550; ENSG00000167996.
DR GeneID; 2495; -.
DR KEGG; hsa:2495; -.
DR UCSC; uc001nsu.3; human.
DR CTD; 2495; -.
DR GeneCards; GC11M061731; -.
DR H-InvDB; HIX0128677; -.
DR H-InvDB; HIX0200367; -.
DR HGNC; HGNC:3976; FTH1.
DR HPA; CAB008623; -.
DR HPA; HPA043650; -.
DR MIM; 134770; gene+phenotype.
DR neXtProt; NX_P02794; -.
DR Orphanet; 247790; FTH1-related iron overload.
DR PharmGKB; PA28392; -.
DR eggNOG; COG1528; -.
DR HOVERGEN; HBG000410; -.
DR InParanoid; P02794; -.
DR KO; K00522; -.
DR OMA; AMAYHFD; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR ChiTaRS; FTH1; human.
DR EvolutionaryTrace; P02794; -.
DR GeneWiki; FTH1; -.
DR GenomeRNAi; 2495; -.
DR NextBio; 9857; -.
DR PRO; PR:P02794; -.
DR ArrayExpress; P02794; -.
DR Bgee; P02794; -.
DR CleanEx; HS_FTH1; -.
DR Genevestigator; P02794; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008043; C:intracellular ferritin complex; TAS:ProtInc.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0008199; F:ferric iron binding; IEA:InterPro.
DR GO; GO:0004322; F:ferroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR GO; GO:0006880; P:intracellular sequestering of iron ion; IDA:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; IEA:InterPro.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR Gene3D; 1.20.1260.10; -; 1.
DR InterPro; IPR001519; Ferritin.
DR InterPro; IPR009040; Ferritin-like_diiron.
DR InterPro; IPR009078; Ferritin-like_SF.
DR InterPro; IPR012347; Ferritin-rel.
DR InterPro; IPR014034; Ferritin_CS.
DR InterPro; IPR008331; Ferritin_DPS_dom.
DR PANTHER; PTHR11431; PTHR11431; 1.
DR Pfam; PF00210; Ferritin; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00540; FERRITIN_1; 1.
DR PROSITE; PS00204; FERRITIN_2; 1.
DR PROSITE; PS50905; FERRITIN_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Iron; Iron storage;
KW Metal-binding; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1 183 Ferritin heavy chain.
FT /FTId=PRO_0000201048.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 183 Ferritin heavy chain, N-terminally
FT processed.
FT /FTId=PRO_0000424472.
FT DOMAIN 11 160 Ferritin-like diiron.
FT METAL 28 28 Iron 1.
FT METAL 63 63 Iron 1.
FT METAL 63 63 Iron 2.
FT METAL 66 66 Iron 1.
FT METAL 108 108 Iron 2.
FT METAL 142 142 Iron 2.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Ferritin heavy
FT chain, N-terminally processed.
FT MOD_RES 179 179 Phosphoserine.
FT MOD_RES 183 183 Phosphoserine.
FT CONFLICT 176 183 LGDSDNES -> WETVIMKAKPRANFP (in Ref. 1;
FT CAA25086).
FT HELIX 15 42
FT TURN 45 47
FT HELIX 50 77
FT HELIX 97 124
FT HELIX 128 137
FT HELIX 139 159
FT TURN 160 163
FT HELIX 165 174
SQ SEQUENCE 183 AA; 21226 MW; FEF75640A29CCF56 CRC64;
MTTASTSQVR QNYHQDSEAA INRQINLELY ASYVYLSMSY YFDRDDVALK NFAKYFLHQS
HEEREHAEKL MKLQNQRGGR IFLQDIKKPD CDDWESGLNA MECALHLEKN VNQSLLELHK
LATDKNDPHL CDFIETHYLN EQVKAIKELG DHVTNLRKMG APESGLAEYL FDKHTLGDSD
NES
//
ID FRIH_HUMAN Reviewed; 183 AA.
AC P02794; B3KNR5; Q3KRA8; Q3SWW1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Ferritin heavy chain;
DE Short=Ferritin H subunit;
DE EC=1.16.3.1;
DE AltName: Full=Cell proliferation-inducing gene 15 protein;
DE Contains:
DE RecName: Full=Ferritin heavy chain, N-terminally processed;
GN Name=FTH1; Synonyms=FTH, FTHL6; ORFNames=OK/SW-cl.84, PIG15;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hepatocyte;
RX PubMed=6323167;
RA Costanzo F., Santoro C., Colantuoni V., Bensi G., Raugei G.,
RA Romano V., Cortese R.;
RT "Cloning and sequencing of a full length cDNA coding for a human
RT apoferritin H chain: evidence for a multigene family.";
RL EMBO J. 3:23-27(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3840162;
RA Boyd D., Vecoli C., Belcher D.M., Jain S.K., Drysdale J.W.;
RT "Structural and functional relationships of human ferritin H and L
RT chains deduced from cDNA clones.";
RL J. Biol. Chem. 260:11755-11761(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3023856;
RA Chou C.-C., Gatti R.A., Fuller M.L., Concannon P., Wong A., Chada S.,
RA Davis R.C., Salser W.A.;
RT "Structure and expression of ferritin genes in a human promyelocytic
RT cell line that differentiates in vitro.";
RL Mol. Cell. Biol. 6:566-573(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3003694; DOI=10.1093/nar/14.2.721;
RA Costanzo F., Colombo M., Staempfli S., Santoro C., Marone M.,
RA Frank R., Delius H., Cortese R.;
RT "Structure of gene and pseudogenes of human apoferritin H.";
RL Nucleic Acids Res. 14:721-736(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3020541; DOI=10.1073/pnas.83.19.7226;
RA Hentze M.W., Keim S., Papadopoulos P., O'Brien S., Modi W.,
RA Drysdale J.W., Leonard W.J., Harford J.B., Klausner R.D.;
RT "Cloning, characterization, expression, and chromosomal localization
RT of a human ferritin heavy-chain gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7226-7230(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7916709; DOI=10.1016/0378-1119(93)90380-L;
RA Dhar M., Chauthaiwale V.M., Joshi J.G.;
RT "Sequence of a cDNA encoding the ferritin H-chain from an 11-week-old
RT human fetal brain.";
RL Gene 126:275-278(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Chauthaiwale V.M., Dhar M., McLachlan D.R., Joshi J.G.;
RT "Cloning of a novel full length cDNA for ferritin heavy chain from
RT normal adult human and Alzheimer's brain.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Franco A.V., Gray C.P., Myers K., Hersey P.;
RT "Detection of ferritin heavy chain by SEREX: a multifunctional
RT molecule in malignant tumour cells.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation gene 15.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Cervix, Colon, Lung, Ovary, Prostate, and
RC Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 128-183.
RX PubMed=6589621; DOI=10.1073/pnas.81.15.4751;
RA Boyd D., Jain S.K., Crampton J., Barrett K.J., Drysdale J.;
RT "Isolation and characterization of a cDNA clone for human ferritin
RT heavy chain.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4751-4755(1984).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179 AND SER-183, AND
RP MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=1992356; DOI=10.1038/349541a0;
RA Lawson D.M., Artymiuk P.J., Yewdall S.J., Smith J.M.A.,
RA Livingstone J.C., Treffry A., Luzzago A., Levi S., Arosio P.,
RA Cesarini G., Thomas C.D., Shaw W.V., Harrison P.M.;
RT "Solving the structure of human H ferritin by genetically engineering
RT intermolecular crystal contacts.";
RL Nature 349:541-544(1991).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=9159481; DOI=10.1006/jmbi.1997.0970;
RA Hempstead P.D., Yewdall S.J., Fernie A.R., Lawson D.M., Artymiuk P.J.,
RA Rice D.W., Ford G.C., Harrison P.M.;
RT "Comparison of the three-dimensional structures of recombinant human H
RT and horse L ferritins at high resolution.";
RL J. Mol. Biol. 268:424-448(1997).
CC -!- FUNCTION: Stores iron in a soluble, non-toxic, readily available
CC form. Important for iron homeostasis. Has ferroxidase activity.
CC Iron is taken up in the ferrous form and deposited as ferric
CC hydroxides after oxidation. Also plays a role in delivery of iron
CC to cells. Mediates iron uptake in capsule cells of the developing
CC kidney (By similarity).
CC -!- CATALYTIC ACTIVITY: 4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O.
CC -!- SUBUNIT: Oligomer of 24 subunits. There are two types of subunits:
CC L (light) chain and H (heavy) chain. The major chain can be light
CC or heavy, depending on the species and tissue type. The functional
CC molecule forms a roughly spherical shell with a diameter of 12 nm
CC and contains a central cavity into which the insoluble mineral
CC iron core is deposited.
CC -!- INTERACTION:
CC Q9UER7:DAXX; NbExp=5; IntAct=EBI-713259, EBI-77321;
CC P02792:FTL; NbExp=3; IntAct=EBI-713259, EBI-713279;
CC P61244:MAX; NbExp=2; IntAct=EBI-713259, EBI-751711;
CC -!- MISCELLANEOUS: In human liver the heavy chain is the major chain.
CC -!- SIMILARITY: Belongs to the ferritin family.
CC -!- SIMILARITY: Contains 1 ferritin-like diiron domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI05803.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ferritin entry;
CC URL="http://en.wikipedia.org/wiki/Ferritin";
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DR EMBL; X00318; CAA25086.1; -; mRNA.
DR EMBL; M11146; AAA52437.1; -; mRNA.
DR EMBL; M12937; AAA35830.1; -; mRNA.
DR EMBL; X03487; CAA27205.1; -; Genomic_DNA.
DR EMBL; X03488; CAA27205.1; JOINED; Genomic_DNA.
DR EMBL; M14212; AAA52438.1; -; Genomic_DNA.
DR EMBL; M14211; AAA52438.1; JOINED; Genomic_DNA.
DR EMBL; M97164; AAA35832.1; -; mRNA.
DR EMBL; L20941; AAA35833.1; -; mRNA.
DR EMBL; AF088851; AAF89523.1; -; mRNA.
DR EMBL; AY258285; AAP82230.1; -; mRNA.
DR EMBL; AB062402; BAB93489.1; -; mRNA.
DR EMBL; AK054816; BAG51427.1; -; mRNA.
DR EMBL; DQ496108; ABF47097.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW73989.1; -; Genomic_DNA.
DR EMBL; BC000857; AAH00857.1; -; mRNA.
DR EMBL; BC001399; AAH01399.1; -; mRNA.
DR EMBL; BC011359; AAH11359.1; -; mRNA.
DR EMBL; BC013724; AAH13724.1; -; mRNA.
DR EMBL; BC015156; AAH15156.1; -; mRNA.
DR EMBL; BC016009; AAH16009.1; -; mRNA.
DR EMBL; BC016857; AAH16857.1; -; mRNA.
DR EMBL; BC063514; AAH63514.1; -; mRNA.
DR EMBL; BC066961; AAH66961.1; -; mRNA.
DR EMBL; BC073750; AAH73750.1; -; mRNA.
DR EMBL; BC104643; AAI04644.1; -; mRNA.
DR EMBL; BC105802; AAI05803.1; ALT_INIT; mRNA.
DR EMBL; M15383; AAA52479.1; -; mRNA.
DR PIR; A23517; FRHUH.
DR RefSeq; NP_002023.2; NM_002032.2.
DR RefSeq; XP_005273922.1; XM_005273865.1.
DR UniGene; Hs.524910; -.
DR UniGene; Hs.645560; -.
DR PDB; 1FHA; X-ray; 2.40 A; A=1-183.
DR PDB; 2CEI; X-ray; 1.80 A; A=2-182.
DR PDB; 2CHI; X-ray; 1.60 A; A=2-182.
DR PDB; 2CIH; X-ray; 1.50 A; A=2-182.
DR PDB; 2CLU; X-ray; 2.10 A; A=2-182.
DR PDB; 2CN6; X-ray; 2.20 A; A=2-182.
DR PDB; 2CN7; X-ray; 1.75 A; A=2-182.
DR PDB; 2FHA; X-ray; 1.90 A; A=1-183.
DR PDB; 2IU2; X-ray; 1.80 A; A=2-182.
DR PDB; 2Z6M; X-ray; 2.72 A; A/B/C/D/E/F/G/H/I/J/K/L=2-177.
DR PDB; 3AJO; X-ray; 1.52 A; A=2-183.
DR PDB; 3AJP; X-ray; 1.90 A; A=2-183.
DR PDB; 3AJQ; X-ray; 1.58 A; A=2-183.
DR PDB; 3ERZ; X-ray; 3.06 A; A/B/C/D/E/F/G/H/I/J/K/L=1-183.
DR PDB; 3ES3; X-ray; 2.79 A; A=1-183.
DR PDB; 4DYX; X-ray; 1.85 A; A=6-177.
DR PDB; 4DYY; X-ray; 1.90 A; A=6-177.
DR PDB; 4DYZ; X-ray; 2.30 A; A=6-177.
DR PDB; 4DZ0; X-ray; 2.50 A; A=6-177.
DR PDBsum; 1FHA; -.
DR PDBsum; 2CEI; -.
DR PDBsum; 2CHI; -.
DR PDBsum; 2CIH; -.
DR PDBsum; 2CLU; -.
DR PDBsum; 2CN6; -.
DR PDBsum; 2CN7; -.
DR PDBsum; 2FHA; -.
DR PDBsum; 2IU2; -.
DR PDBsum; 2Z6M; -.
DR PDBsum; 3AJO; -.
DR PDBsum; 3AJP; -.
DR PDBsum; 3AJQ; -.
DR PDBsum; 3ERZ; -.
DR PDBsum; 3ES3; -.
DR PDBsum; 4DYX; -.
DR PDBsum; 4DYY; -.
DR PDBsum; 4DYZ; -.
DR PDBsum; 4DZ0; -.
DR ProteinModelPortal; P02794; -.
DR SMR; P02794; 6-177.
DR DIP; DIP-38301N; -.
DR IntAct; P02794; 28.
DR MINT; MINT-4822446; -.
DR STRING; 9606.ENSP00000273550; -.
DR DrugBank; DB00893; Iron Dextran.
DR PhosphoSite; P02794; -.
DR DMDM; 120516; -.
DR UCD-2DPAGE; P02794; -.
DR PaxDb; P02794; -.
DR PRIDE; P02794; -.
DR DNASU; 2495; -.
DR Ensembl; ENST00000273550; ENSP00000273550; ENSG00000167996.
DR GeneID; 2495; -.
DR KEGG; hsa:2495; -.
DR UCSC; uc001nsu.3; human.
DR CTD; 2495; -.
DR GeneCards; GC11M061731; -.
DR H-InvDB; HIX0128677; -.
DR H-InvDB; HIX0200367; -.
DR HGNC; HGNC:3976; FTH1.
DR HPA; CAB008623; -.
DR HPA; HPA043650; -.
DR MIM; 134770; gene+phenotype.
DR neXtProt; NX_P02794; -.
DR Orphanet; 247790; FTH1-related iron overload.
DR PharmGKB; PA28392; -.
DR eggNOG; COG1528; -.
DR HOVERGEN; HBG000410; -.
DR InParanoid; P02794; -.
DR KO; K00522; -.
DR OMA; AMAYHFD; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR ChiTaRS; FTH1; human.
DR EvolutionaryTrace; P02794; -.
DR GeneWiki; FTH1; -.
DR GenomeRNAi; 2495; -.
DR NextBio; 9857; -.
DR PRO; PR:P02794; -.
DR ArrayExpress; P02794; -.
DR Bgee; P02794; -.
DR CleanEx; HS_FTH1; -.
DR Genevestigator; P02794; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008043; C:intracellular ferritin complex; TAS:ProtInc.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0008199; F:ferric iron binding; IEA:InterPro.
DR GO; GO:0004322; F:ferroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR GO; GO:0006880; P:intracellular sequestering of iron ion; IDA:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; IEA:InterPro.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR Gene3D; 1.20.1260.10; -; 1.
DR InterPro; IPR001519; Ferritin.
DR InterPro; IPR009040; Ferritin-like_diiron.
DR InterPro; IPR009078; Ferritin-like_SF.
DR InterPro; IPR012347; Ferritin-rel.
DR InterPro; IPR014034; Ferritin_CS.
DR InterPro; IPR008331; Ferritin_DPS_dom.
DR PANTHER; PTHR11431; PTHR11431; 1.
DR Pfam; PF00210; Ferritin; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00540; FERRITIN_1; 1.
DR PROSITE; PS00204; FERRITIN_2; 1.
DR PROSITE; PS50905; FERRITIN_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Iron; Iron storage;
KW Metal-binding; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1 183 Ferritin heavy chain.
FT /FTId=PRO_0000201048.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 183 Ferritin heavy chain, N-terminally
FT processed.
FT /FTId=PRO_0000424472.
FT DOMAIN 11 160 Ferritin-like diiron.
FT METAL 28 28 Iron 1.
FT METAL 63 63 Iron 1.
FT METAL 63 63 Iron 2.
FT METAL 66 66 Iron 1.
FT METAL 108 108 Iron 2.
FT METAL 142 142 Iron 2.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Ferritin heavy
FT chain, N-terminally processed.
FT MOD_RES 179 179 Phosphoserine.
FT MOD_RES 183 183 Phosphoserine.
FT CONFLICT 176 183 LGDSDNES -> WETVIMKAKPRANFP (in Ref. 1;
FT CAA25086).
FT HELIX 15 42
FT TURN 45 47
FT HELIX 50 77
FT HELIX 97 124
FT HELIX 128 137
FT HELIX 139 159
FT TURN 160 163
FT HELIX 165 174
SQ SEQUENCE 183 AA; 21226 MW; FEF75640A29CCF56 CRC64;
MTTASTSQVR QNYHQDSEAA INRQINLELY ASYVYLSMSY YFDRDDVALK NFAKYFLHQS
HEEREHAEKL MKLQNQRGGR IFLQDIKKPD CDDWESGLNA MECALHLEKN VNQSLLELHK
LATDKNDPHL CDFIETHYLN EQVKAIKELG DHVTNLRKMG APESGLAEYL FDKHTLGDSD
NES
//
MIM
134770
*RECORD*
*FIELD* NO
134770
*FIELD* TI
*134770 FERRITIN HEAVY CHAIN 1; FTH1
;;FTH;;
FHC;;
FTHL6
*FIELD* TX
See ferritin light chain (134790).
read more
CLONING
Murray et al. (1987) demonstrated that the rat has a single H-subunit
gene. Near the cap region of the 5-prime untranslated region, this
subunit shows a 28-nucleotide sequence that is almost totally conserved
in human, bullfrog, and chicken H mRNA and is also faithfully
represented in the rat and human L-subunit mRNAs. This sequence is a
prime candidate for involvement in the known translational regulation of
both subunits by iron, which induces synthesis of the subunits by
causing latent mRNAs present in the cytosol to become
polyribosome-associated and translationally active.
Hentze et al. (1986) isolated a genomic phage clone containing a
full-length copy of the gene for ferritin heavy chain. The functionality
of the gene was demonstrated by the fact that both transient
transfectants and stable transformants of mouse fibroblasts actively
transcribed human ferritin heavy-chain mRNA.
GENE STRUCTURE
Hentze et al. (1986) determined that the FTH1 gene consists of 4 exons
and spans approximately 3 kb.
From genomic analysis, using a cDNA clone, Boyd et al. (1984) concluded
that the ferritin heavy chains are either encoded by a multigene family
or that the gene has an unusually large number of exons.
MAPPING
By study of hamster-human and mouse-human hybrid cells, some with
translocations involving chromosome 19, Worwood et al. (1985) concluded
that light subunits of ferritin (rich in human spleen ferritin) are
coded by a gene in segment 19q13.3-qter and that the gene for the heavy
subunit (rich in human heart ferritin) is located on chromosome 11.
By study of DNA extracted from rodent-human cell hybrids, Cragg et al.
(1985) found sequences homologous to a probe for the H subunit of human
ferritin on at least 8 chromosomes: 1, 2, 3, 6p21-6cen, 11, 14, 20, and
Xq23-Xqter. Only the gene on chromosome 11 appeared to be expressed in
these hybrids.
Hentze et al. (1986) assigned the human FTH1 gene to chromosome 11 by
analysis of genomic DNA from rodent-human cell hybrids.
Gatti et al. (1987) concluded that the heavy-subunit family includes 15
to 20 genes or pseudogenes and that the light-subunit family includes at
least 3 genes. They confirmed and extended the chromosomal localization
of the heavy-subunit 'genes' to chromosomes 1-6, 8, 9, 11, 13, 14, 17,
and X. They identified and characterized a BamHI RFLP of FTH located on
chromosome 3. Two alleles were identified and the polymorphic
information content was calculated to be 0.34. Gatti et al. (1987)
discussed the possibility that gene-family probes that hybridize to many
discrete members of dispersed gene families might be useful in
conjunction with pulsed- or inverted-field gels to screen a large number
of specific genomic regions for microdeletions.
Using in situ hybridization, Yachou et al. (1991) demonstrated that
mouse ferritin H-related sequences map to murine chromosomes 3, 6, and
19. Syntenic homology suggested that the chromosome 19 sequence
corresponds to the structural H gene. Yachou et al. (1991) demonstrated
that ferritin H represents a multigene family, that it is polymorphic,
and that there is a single multiallelic functional gene on mouse
chromosome 19 in a region of conserved synteny with human chromosome
11q. Richard et al. (1991) described a high resolution radiation hybrid
map of 11q12-q13, which placed FTH1 between the PGA cluster (see 169710)
and COX8 (123870). In pulsed field gel electrophoresis studies, Gailani
et al. (1991) found that C1NH (606860) and FTH1 lie in the same DNA
fragment that is less than or equal to 48 kb. Papadopoulos et al. (1992)
identified a second ferritin heavy chain gene on chromosome 11, FTH2,
which in situ hybridization indicated lies close to FTH1. Whether this
is a functional gene remained to be determined.
Courseaux et al. (1996) used a combination of methods to refine maps of
an approximately 5-Mb region of 11q13. They proposed the following gene
order:
cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM,
ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel.
GENE FUNCTION
Wu et al. (1999) demonstrated that c-myc (190080) represses the
expression of ferritin-H.
Pham et al. (2004) identified FTH1, the primary iron storage factor, as
an essential mediator of the antioxidant and protective activities of
nuclear factor kappa-B (NFKB; see 164011). They determined that FTH1 is
induced downstream of NFKB and is required to prevent sustained JNK (see
601158) activation and, thereby, apoptosis triggered by tumor necrosis
factor (TNF; 191160). FTH1-mediated inhibition of JNK signaling depended
on suppressing reactive oxygen species accumulation and was achieved
through iron sequestration.
Human ferritins expressed in yeast normally contain little iron, which
led Shi et al. (2008) to hypothesize that yeast, which do not express
ferritins, might also lack the requisite iron chaperones needed for
delivery of iron to ferritin. In a genetic screen to identify human
genes that, when expressed in yeast, could increase the amount of iron
loaded into ferritin, Shi et al. (2008) identified poly(rC) binding
protein-1 (PCBP1; 601209). PCBP1 bound to ferritin in vivo and bound
iron and facilitated iron loading into ferritin in vitro. Depletion of
PCBP1 in human cells inhibited ferritin iron loading and increased
cytosolic iron pools. Thus, Shi et al. (2008) concluded that PCBP1 can
function as a cytosolic iron chaperone in the delivery of iron to
ferritin.
For a review of the ferritins, including their molecular properties,
iron storage function, and cellular regulation, see Harrison and Arosio
(1996).
MOLECULAR GENETICS
Synthesis of both the H- and L-ferritin subunits is controlled by a
common cytosolic protein, iron regulatory protein (IRP), which binds to
the iron-responsive element (IRE) in the 5-prime untranslated region of
the H- and L-ferritin mRNAs (Leibold and Munro, 1988; Eisenstein, 2000).
In 4 of 7 members of a Japanese family affected by dominantly inherited
iron overload, Kato et al. (2001) found a single point mutation
(134770.0001) in the IRE motif of H ferritin mRNA. Gel-shift mobility
assay and Scatchard-plot analysis revealed that a mutated IRE probe had
a higher binding affinity to IRP than did the wildtype probe. When
mutated H subunit was overexpressed in COS-1 cells, suppression of
H-subunit synthesis and of the increment of radiolabeled iron uptake
were observed. These data suggested that the point mutation in the IRE
of H-subunit is responsible for tissue iron deposition and is a novel
cause of hereditary iron overload, most likely related to impairment of
the ferroxidase activity generated by H subunit.
ANIMAL MODEL
Ferreira et al. (2000) disrupted the H ferritin gene in mice by
homologous recombination. Heterozygous mice were healthy, fertile, and
did not differ significantly from their control littermates. However,
Fth -/- embryos died between 3.5 and 9.5 days of development, suggesting
that there is no functional redundancy between the 2 ferritin subunits
and that, in the absence of H subunits, L ferritin homopolymers are not
able to maintain iron in a bioavailable and nontoxic form. The pattern
of expression of the wildtype Fth gene in 9.5-day embryos is restricted
to the developing heart and central nervous system.
The results of an analysis of H ferritin knockout mice by Ferreira et
al. (2001) raised the possibility that reduced H ferritin expression may
be responsible for unexplained human cases of hyperferritinemia in the
absence of iron overload where the hereditary hyperferritinemia-cataract
syndrome (600886) has been excluded. Heterozygous H ferritin knockout
mice had slightly elevated tissue L ferritin content and 7- to 10-fold
more L ferritin in the serum than normal mice, but their serum iron
remained unchanged. H ferritin synthesis from the remaining allele was
not upregulated.
HISTORY
Ferritin of liver and spleen contains mostly L subunits. Antibodies to
liver or spleen ferritin are not likely to detect ferritin containing
only H subunits. This may explain the conclusion of Caskey et al. (1983)
that both subunits are coded by chromosome 19. Heart ferritin contains a
preponderance of H subunits. (According to Costanzo et al. (1986), the 2
types of apoferritin subunits were designated H and L for heart and
liver, respectively.) Contrary to the earlier impression that both the
heavy and light chains of ferritin are encoded by chromosome 19, McGill
et al. (1984) by in situ hybridization localized the L gene to 19 (as
previously) and the H gene to 1p.
Using a heavy chain probe of Boyd et al. (1984), Youssoufian et al.
(1988) concluded that one FTH gene is in the segment 1q32.3-q42.3. In a
patient with deletion of this segment, a reduced hybridization signal
with the FTH probe was observed. The gene may be nonfunctional (i.e., a
pseudogene).
*FIELD* AV
.0001
HEMOCHROMATOSIS, TYPE 5 (1 family)
FTH1, 5-PRIME UTR, A-T, +49
Kato et al. (2001) studied a Japanese family segregating autosomal
dominant primary iron overload (HFE5; 615517). The proband was a
56-year-old woman who was incidentally found to have iron overload. A
brother, 2 sisters, and a daughter of 1 of the sisters were affected.
The father of the 3 affected sibs was deceased; the mother was
apparently unaffected. After excluding other causes of iron overload,
they sequenced H- and L-ferritin cDNAs. In the sequence of H subunit
mRNA, they found a heterozygous single A-to-U conversion at position 49
in the second residue of the 5-base IRE loop sequence. The mutation was
found in the genomic DNA of the 4 affected members of the family but not
in 42 unrelated normal subjects.
*FIELD* RF
1. Boyd, D.; Jain, S. K.; Crampton, J.; Barrett, K. J.; Drysdale,
J.: Isolation and characterization of a cDNA clone for human ferritin
heavy chain. Proc. Nat. Acad. Sci. 81: 4751-4755, 1984.
2. Caskey, J. H.; Jones, C.; Miller, Y. E.; Seligman, P. A.: Human
ferritin gene is assigned to chromosome 19. Proc. Nat. Acad. Sci. 80:
482-486, 1983.
3. Costanzo, F.; Colombo, M.; Staempfli, S.; Santoro, C.; Marone,
M.; Frank, R.; Delius, H.; Cortese, R.: Structure of gene and pseudogenes
of human apoferritin H. Nucleic Acids Res. 14: 721-736, 1986.
4. Courseaux, A.; Grosgeorge, J.; Gaudray, P.; Pannett, A. A. J.;
Forbes, S. A.; Williamson, C.; Bassett, D.; Thakker, R. V.; Teh, B.
T.; Farnebo, F.; Shepherd, J.; Skogseid, B.; Larsson, C.; Giraud,
S.; Zhang, C. X.; Salandre, J.; Calender, A.: Definition of the minimal
MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. Genomics 37:
354-365, 1996.
5. Cragg, S. J.; Drysdale, J.; Worwood, M.: Genes for the 'H' subunit
of human ferritin are present on a number of human chromosomes. Hum.
Genet. 71: 108-112, 1985.
6. Eisenstein, R. S.: Iron regulatory proteins and the molecular
control of mammalian iron metabolism. Annu. Rev. Nutr. 20: 627-662,
2000.
7. Ferreira, C.; Bucchini, D.; Martin, M.-E.; Levi, S.; Arosio, P.;
Grandchamp, B.; Beaumont, C.: Early embryonic lethality of H ferritin
gene deletion in mice. J. Biol. Chem. 275: 3021-3024, 2000.
8. Ferreira, C.; Santambrogio, P.; Martin, M.-E.; Andrieu, V.; Feldmann,
G.; Henin, D.; Beaumont, C.: H ferritin knockout mice: a model of
hyperferritinemia in the absence of iron overload. Blood 98: 525-532,
2001.
9. Gailani, M. R.; Petty, E. M.; Horsthemke, B.; Arnold, A.; Marx,
S. J.; Bale, A. E.: Physical mapping of chromosome 11q12-13 by pulsed
field gel electrophoresis (PFGE). (Abstract) Cytogenet. Cell Genet. 58:
1959 only, 1991.
10. Gatti, R. A.; Shaked, R.; Mohandas, T. K.; Salser, W.: Human
ferritin genes: chromosomal assignments and polymorphisms. Am. J.
Hum. Genet. 41: 654-667, 1987.
11. Harrison, P. M.; Arosio, P.: The ferritins: molecular properties,
iron storage function and cellular regulation. Biochim. Biophys.
Acta 1275: 161-203, 1996.
12. Hentze, M. W.; Keim, S.; Papadopoulos, P.; O'Brien, S.; Modi,
W.; Drysdale, J.; Leonard, W. J.; Harford, J. B.; Klausner, R. D.
: Cloning, characterization, expression, and chromosomal localization
of a human ferritin heavy-chain gene. Proc. Nat. Acad. Sci. 83:
7226-7230, 1986.
13. Kato, J.; Fujikawa, K.; Kanda, M.; Fukuda, N.; Sasaki, K.; Takayama,
T.; Kobune, M.; Takada, K.; Takimoto, R.; Hamada, H.; Ikeda, T.; Niitsu,
Y.: A mutation, in the iron-responsive element of H ferritin mRNA,
causing autosomal dominant iron overload. Am. J. Hum. Genet. 69:
191-197, 2001.
14. Leibold, E. A.; Munro, H. N.: Cytoplasmic protein binds in vitro
to a highly conserved sequence in the 5-prime untranslated region
of ferritin heavy- and light-subunit mRNAs. Proc. Nat. Acad. Sci. 85:
2171-2175, 1988.
15. McGill, J. R.; Boyd, D.; Barrett, K. J.; Drysdale, J. W.; Moore,
C. M.: Localization of human ferritin H (heavy) and L (light) subunits
by in situ hybridization. (Abstract) Am. J. Hum. Genet. 36: 146S
only, 1984.
16. Murray, M. T.; White, K.; Munro, H. N.: Conservation of ferritin
heavy subunit gene structure: implications for the regulation of ferritin
gene expression. Proc. Nat. Acad. Sci. 84: 7438-7442, 1987.
17. Papadopoulos, P.; Bhavsar, D.; Zappone, E.; David, V.; Jones,
C.; Worwood, M.; Drysdale, J.: A second human ferritin H locus on
chromosome 11. Cytogenet. Cell Genet. 61: 107-108, 1992.
18. Pham, C. G.; Bubici, C.; Zazzeroni, F.; Papa, S.; Jones, J.; Alvarez,
K.; Jayawardena, S.; De Smaele, E.; Cong, R.; Beaumont, C.; Torti,
F. M.; Torti, S. V.; Franzoso, G.: Ferritin heavy chain upregulation
by NF-kappa-B inhibits TNF-alpha-induced apoptosis by suppressing
reactive oxygen species. Cell 119: 529-542, 2004.
19. Richard, C. W.; Withers, D. A.; Meeker, T. C.; Myers, R. M.:
A radiation hybrid map of the proximal long arm of human chromosome
11 containing the MEN-1 and bcl-1 disease locus. (Abstract) Cytogenet.
Cell Genet. 58: 1970 only, 1991.
20. Shi, H.; Bencze, K. Z.; Stemmler, T. L.; Philpott, C. C.: A cytosolic
iron chaperone that delivers iron to ferritin. Science 320: 1207-1210,
2008.
21. Worwood, M.; Brook, J. D.; Cragg, S. J.; Hellkuhl, B.; Jones,
B. M.; Perera, P.; Roberts, S. H.; Shaw, D. J.: Assignment of human
ferritin genes to chromosomes 11 and 19q13.3-19qter. Hum. Genet. 69:
371-374, 1985.
22. Wu, K.-J.; Polack, A.; Dalla-Favera, R.: Coordinated regulation
of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283:
676-679, 1999.
23. Yachou, A.; Mattei, M. G.; Roeckel, N.; Grandchamp, B.; Beaumont,
C.: Mouse ferritin H sequences map to chromosomes 3, 6, and 19. Genomics 9:
204-206, 1991.
24. Yachou, A.-K.; Renaudie, F.; Guenet, J.-L.; Simon-Chazottes, D.;
Jones, R.; Grandchamp, B.; Beaumont, C.: Mouse ferritin H multigene
family is polymorphic and contains a single multiallelic functional
gene located on chromosome 19. Genomics 10: 531-538, 1991.
25. Youssoufian, H.; Chance, P.; Tuck-Muller, C. M.; Jabs, E. W.:
Association of a new chromosomal deletion [del(1)(q32q42)] with diaphragmatic
hernia: assignment of a human ferritin gene. Hum. Genet. 78: 267-270,
1988.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/6/2013
Ada Hamosh - updated: 6/10/2008
Stylianos E. Antonarakis - updated: 1/4/2005
Victor A. McKusick - updated: 12/5/2001
Victor A. McKusick - updated: 8/16/2001
Ada Hamosh - updated: 2/11/2000
Ada Hamosh - updated: 3/4/1999
Ada Hamosh - updated: 1/29/1999
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/06/2013
carol: 11/6/2013
carol: 11/4/2013
carol: 2/9/2011
alopez: 6/12/2008
terry: 6/10/2008
mgross: 1/4/2005
terry: 7/19/2004
mgross: 3/17/2004
terry: 6/26/2002
carol: 4/25/2002
carol: 12/10/2001
mcapotos: 12/5/2001
cwells: 9/7/2001
cwells: 8/27/2001
terry: 8/16/2001
alopez: 2/15/2000
terry: 2/11/2000
alopez: 3/4/1999
alopez: 1/29/1999
joanna: 8/6/1997
terry: 8/5/1997
mimadm: 9/24/1994
carol: 12/21/1992
supermim: 3/16/1992
carol: 3/4/1992
carol: 2/22/1992
carol: 10/10/1991
*RECORD*
*FIELD* NO
134770
*FIELD* TI
*134770 FERRITIN HEAVY CHAIN 1; FTH1
;;FTH;;
FHC;;
FTHL6
*FIELD* TX
See ferritin light chain (134790).
read more
CLONING
Murray et al. (1987) demonstrated that the rat has a single H-subunit
gene. Near the cap region of the 5-prime untranslated region, this
subunit shows a 28-nucleotide sequence that is almost totally conserved
in human, bullfrog, and chicken H mRNA and is also faithfully
represented in the rat and human L-subunit mRNAs. This sequence is a
prime candidate for involvement in the known translational regulation of
both subunits by iron, which induces synthesis of the subunits by
causing latent mRNAs present in the cytosol to become
polyribosome-associated and translationally active.
Hentze et al. (1986) isolated a genomic phage clone containing a
full-length copy of the gene for ferritin heavy chain. The functionality
of the gene was demonstrated by the fact that both transient
transfectants and stable transformants of mouse fibroblasts actively
transcribed human ferritin heavy-chain mRNA.
GENE STRUCTURE
Hentze et al. (1986) determined that the FTH1 gene consists of 4 exons
and spans approximately 3 kb.
From genomic analysis, using a cDNA clone, Boyd et al. (1984) concluded
that the ferritin heavy chains are either encoded by a multigene family
or that the gene has an unusually large number of exons.
MAPPING
By study of hamster-human and mouse-human hybrid cells, some with
translocations involving chromosome 19, Worwood et al. (1985) concluded
that light subunits of ferritin (rich in human spleen ferritin) are
coded by a gene in segment 19q13.3-qter and that the gene for the heavy
subunit (rich in human heart ferritin) is located on chromosome 11.
By study of DNA extracted from rodent-human cell hybrids, Cragg et al.
(1985) found sequences homologous to a probe for the H subunit of human
ferritin on at least 8 chromosomes: 1, 2, 3, 6p21-6cen, 11, 14, 20, and
Xq23-Xqter. Only the gene on chromosome 11 appeared to be expressed in
these hybrids.
Hentze et al. (1986) assigned the human FTH1 gene to chromosome 11 by
analysis of genomic DNA from rodent-human cell hybrids.
Gatti et al. (1987) concluded that the heavy-subunit family includes 15
to 20 genes or pseudogenes and that the light-subunit family includes at
least 3 genes. They confirmed and extended the chromosomal localization
of the heavy-subunit 'genes' to chromosomes 1-6, 8, 9, 11, 13, 14, 17,
and X. They identified and characterized a BamHI RFLP of FTH located on
chromosome 3. Two alleles were identified and the polymorphic
information content was calculated to be 0.34. Gatti et al. (1987)
discussed the possibility that gene-family probes that hybridize to many
discrete members of dispersed gene families might be useful in
conjunction with pulsed- or inverted-field gels to screen a large number
of specific genomic regions for microdeletions.
Using in situ hybridization, Yachou et al. (1991) demonstrated that
mouse ferritin H-related sequences map to murine chromosomes 3, 6, and
19. Syntenic homology suggested that the chromosome 19 sequence
corresponds to the structural H gene. Yachou et al. (1991) demonstrated
that ferritin H represents a multigene family, that it is polymorphic,
and that there is a single multiallelic functional gene on mouse
chromosome 19 in a region of conserved synteny with human chromosome
11q. Richard et al. (1991) described a high resolution radiation hybrid
map of 11q12-q13, which placed FTH1 between the PGA cluster (see 169710)
and COX8 (123870). In pulsed field gel electrophoresis studies, Gailani
et al. (1991) found that C1NH (606860) and FTH1 lie in the same DNA
fragment that is less than or equal to 48 kb. Papadopoulos et al. (1992)
identified a second ferritin heavy chain gene on chromosome 11, FTH2,
which in situ hybridization indicated lies close to FTH1. Whether this
is a functional gene remained to be determined.
Courseaux et al. (1996) used a combination of methods to refine maps of
an approximately 5-Mb region of 11q13. They proposed the following gene
order:
cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM,
ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel.
GENE FUNCTION
Wu et al. (1999) demonstrated that c-myc (190080) represses the
expression of ferritin-H.
Pham et al. (2004) identified FTH1, the primary iron storage factor, as
an essential mediator of the antioxidant and protective activities of
nuclear factor kappa-B (NFKB; see 164011). They determined that FTH1 is
induced downstream of NFKB and is required to prevent sustained JNK (see
601158) activation and, thereby, apoptosis triggered by tumor necrosis
factor (TNF; 191160). FTH1-mediated inhibition of JNK signaling depended
on suppressing reactive oxygen species accumulation and was achieved
through iron sequestration.
Human ferritins expressed in yeast normally contain little iron, which
led Shi et al. (2008) to hypothesize that yeast, which do not express
ferritins, might also lack the requisite iron chaperones needed for
delivery of iron to ferritin. In a genetic screen to identify human
genes that, when expressed in yeast, could increase the amount of iron
loaded into ferritin, Shi et al. (2008) identified poly(rC) binding
protein-1 (PCBP1; 601209). PCBP1 bound to ferritin in vivo and bound
iron and facilitated iron loading into ferritin in vitro. Depletion of
PCBP1 in human cells inhibited ferritin iron loading and increased
cytosolic iron pools. Thus, Shi et al. (2008) concluded that PCBP1 can
function as a cytosolic iron chaperone in the delivery of iron to
ferritin.
For a review of the ferritins, including their molecular properties,
iron storage function, and cellular regulation, see Harrison and Arosio
(1996).
MOLECULAR GENETICS
Synthesis of both the H- and L-ferritin subunits is controlled by a
common cytosolic protein, iron regulatory protein (IRP), which binds to
the iron-responsive element (IRE) in the 5-prime untranslated region of
the H- and L-ferritin mRNAs (Leibold and Munro, 1988; Eisenstein, 2000).
In 4 of 7 members of a Japanese family affected by dominantly inherited
iron overload, Kato et al. (2001) found a single point mutation
(134770.0001) in the IRE motif of H ferritin mRNA. Gel-shift mobility
assay and Scatchard-plot analysis revealed that a mutated IRE probe had
a higher binding affinity to IRP than did the wildtype probe. When
mutated H subunit was overexpressed in COS-1 cells, suppression of
H-subunit synthesis and of the increment of radiolabeled iron uptake
were observed. These data suggested that the point mutation in the IRE
of H-subunit is responsible for tissue iron deposition and is a novel
cause of hereditary iron overload, most likely related to impairment of
the ferroxidase activity generated by H subunit.
ANIMAL MODEL
Ferreira et al. (2000) disrupted the H ferritin gene in mice by
homologous recombination. Heterozygous mice were healthy, fertile, and
did not differ significantly from their control littermates. However,
Fth -/- embryos died between 3.5 and 9.5 days of development, suggesting
that there is no functional redundancy between the 2 ferritin subunits
and that, in the absence of H subunits, L ferritin homopolymers are not
able to maintain iron in a bioavailable and nontoxic form. The pattern
of expression of the wildtype Fth gene in 9.5-day embryos is restricted
to the developing heart and central nervous system.
The results of an analysis of H ferritin knockout mice by Ferreira et
al. (2001) raised the possibility that reduced H ferritin expression may
be responsible for unexplained human cases of hyperferritinemia in the
absence of iron overload where the hereditary hyperferritinemia-cataract
syndrome (600886) has been excluded. Heterozygous H ferritin knockout
mice had slightly elevated tissue L ferritin content and 7- to 10-fold
more L ferritin in the serum than normal mice, but their serum iron
remained unchanged. H ferritin synthesis from the remaining allele was
not upregulated.
HISTORY
Ferritin of liver and spleen contains mostly L subunits. Antibodies to
liver or spleen ferritin are not likely to detect ferritin containing
only H subunits. This may explain the conclusion of Caskey et al. (1983)
that both subunits are coded by chromosome 19. Heart ferritin contains a
preponderance of H subunits. (According to Costanzo et al. (1986), the 2
types of apoferritin subunits were designated H and L for heart and
liver, respectively.) Contrary to the earlier impression that both the
heavy and light chains of ferritin are encoded by chromosome 19, McGill
et al. (1984) by in situ hybridization localized the L gene to 19 (as
previously) and the H gene to 1p.
Using a heavy chain probe of Boyd et al. (1984), Youssoufian et al.
(1988) concluded that one FTH gene is in the segment 1q32.3-q42.3. In a
patient with deletion of this segment, a reduced hybridization signal
with the FTH probe was observed. The gene may be nonfunctional (i.e., a
pseudogene).
*FIELD* AV
.0001
HEMOCHROMATOSIS, TYPE 5 (1 family)
FTH1, 5-PRIME UTR, A-T, +49
Kato et al. (2001) studied a Japanese family segregating autosomal
dominant primary iron overload (HFE5; 615517). The proband was a
56-year-old woman who was incidentally found to have iron overload. A
brother, 2 sisters, and a daughter of 1 of the sisters were affected.
The father of the 3 affected sibs was deceased; the mother was
apparently unaffected. After excluding other causes of iron overload,
they sequenced H- and L-ferritin cDNAs. In the sequence of H subunit
mRNA, they found a heterozygous single A-to-U conversion at position 49
in the second residue of the 5-base IRE loop sequence. The mutation was
found in the genomic DNA of the 4 affected members of the family but not
in 42 unrelated normal subjects.
*FIELD* RF
1. Boyd, D.; Jain, S. K.; Crampton, J.; Barrett, K. J.; Drysdale,
J.: Isolation and characterization of a cDNA clone for human ferritin
heavy chain. Proc. Nat. Acad. Sci. 81: 4751-4755, 1984.
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*FIELD* CN
Marla J. F. O'Neill - updated: 11/6/2013
Ada Hamosh - updated: 6/10/2008
Stylianos E. Antonarakis - updated: 1/4/2005
Victor A. McKusick - updated: 12/5/2001
Victor A. McKusick - updated: 8/16/2001
Ada Hamosh - updated: 2/11/2000
Ada Hamosh - updated: 3/4/1999
Ada Hamosh - updated: 1/29/1999
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/06/2013
carol: 11/6/2013
carol: 11/4/2013
carol: 2/9/2011
alopez: 6/12/2008
terry: 6/10/2008
mgross: 1/4/2005
terry: 7/19/2004
mgross: 3/17/2004
terry: 6/26/2002
carol: 4/25/2002
carol: 12/10/2001
mcapotos: 12/5/2001
cwells: 9/7/2001
cwells: 8/27/2001
terry: 8/16/2001
alopez: 2/15/2000
terry: 2/11/2000
alopez: 3/4/1999
alopez: 1/29/1999
joanna: 8/6/1997
terry: 8/5/1997
mimadm: 9/24/1994
carol: 12/21/1992
supermim: 3/16/1992
carol: 3/4/1992
carol: 2/22/1992
carol: 10/10/1991