P02794 (FRIH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ferritin heavy chain
Short name=Ferritin H subunit
EC=1.16.3.1

Alternative name(s):
Cell proliferation-inducing gene 15 protein

Gene names

Name:	FTH1
Synonyms:	FTH, FTHL6
ORF Names:	OK/SW-cl.84, PIG15

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	183 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney By similarity.
Catalytic activity	4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O.
Subunit structure	Oligomer of 24 subunits. There are two types of subunits: L (light) chain and H (heavy) chain. The major chain can be light or heavy, depending on the species and tissue type. The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited.
Miscellaneous	In human liver the heavy chain is the major chain.
Sequence similarities	Belongs to the ferritin family. Contains 1 ferritin-like diiron domain.
Sequence caution	The sequence AAI05803.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Iron storage
Ligand	Iron Metal-binding
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome immune response Inferred from sequence or structural similarity. Source: UniProtKB intracellular sequestering of iron ion Inferred from direct assay PubMed 9924025. Source: UniProtKB iron ion transport Inferred from electronic annotation. Source: InterPro negative regulation of fibroblast proliferation Inferred from direct assay PubMed 9924025. Source: UniProtKB post-Golgi vesicle-mediated transport Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome intracellular ferritin complex Traceable author statement Ref.15. Source: ProtInc mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	ferric iron binding Inferred from electronic annotation. Source: InterPro ferroxidase activity Inferred from electronic annotation. Source: EC iron ion binding Traceable author statement Ref.5. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	5	EBI-713259,EBI-77321
MAX	P61244	2	EBI-713259,EBI-751711

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 183

183

Ferritin heavy chain

PRO_0000201048

Regions

Domain

11 – 160

150

Ferritin-like diiron

Sites

Metal binding

28

1

Iron 1

Metal binding

63

1

Iron 1

Metal binding

63

1

Iron 2

Metal binding

66

1

Iron 1

Metal binding

108

1

Iron 2

Metal binding

142

1

Iron 2

Amino acid modifications

Modified residue

179

1

Phosphoserine Ref.16 Ref.18 Ref.19 Ref.21

Modified residue

183

1

Phosphoserine Ref.18

Experimental info

Sequence conflict

176 – 183

8

LGDSDNES → WETVIMKAKPRANFP in CAA25086. Ref.1

Secondary structure

1

.

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.

.

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.

.

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.

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.

.

.

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183

Helix Strand Turn

Details...

Helix

15 – 42

28

Turn

45 – 47

3

Helix

50 – 77

28

Helix

97 – 124

28

Helix

128 – 137

10

Helix

139 – 159

21

Turn

160 – 163

4

Helix

165 – 174

10

Sequences

	Sequence		Length	Mass (Da)
	P02794 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: FEF75640A29CCF56	FASTA	183	21,226
	10 20 30 40 50 60 MTTASTSQVR QNYHQDSEAA INRQINLELY ASYVYLSMSY YFDRDDVALK NFAKYFLHQS 70 80 90 100 110 120 HEEREHAEKL MKLQNQRGGR IFLQDIKKPD CDDWESGLNA MECALHLEKN VNQSLLELHK 130 140 150 160 170 180 LATDKNDPHL CDFIETHYLN EQVKAIKELG DHVTNLRKMG APESGLAEYL FDKHTLGDSD NES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a full length cDNA coding for a human apoferritin H chain: evidence for a multigene family." Costanzo F., Santoro C., Colantuoni V., Bensi G., Raugei G., Romano V., Cortese R. EMBO J. 3:23-27(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hepatocyte.
[2]	"Structural and functional relationships of human ferritin H and L chains deduced from cDNA clones." Boyd D., Vecoli C., Belcher D.M., Jain S.K., Drysdale J.W. J. Biol. Chem. 260:11755-11761(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure and expression of ferritin genes in a human promyelocytic cell line that differentiates in vitro." Chou C.-C., Gatti R.A., Fuller M.L., Concannon P., Wong A., Chada S., Davis R.C., Salser W.A. Mol. Cell. Biol. 6:566-573(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structure of gene and pseudogenes of human apoferritin H." Costanzo F., Colombo M., Staempfli S., Santoro C., Marone M., Frank R., Delius H., Cortese R. Nucleic Acids Res. 14:721-736(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Cloning, characterization, expression, and chromosomal localization of a human ferritin heavy-chain gene." Hentze M.W., Keim S., Papadopoulos P., O'Brien S., Modi W., Drysdale J.W., Leonard W.J., Harford J.B., Klausner R.D. Proc. Natl. Acad. Sci. U.S.A. 83:7226-7230(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Sequence of a cDNA encoding the ferritin H-chain from an 11-week-old human fetal brain." Dhar M., Chauthaiwale V.M., Joshi J.G. Gene 126:275-278(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[7]	"Cloning of a novel full length cDNA for ferritin heavy chain from normal adult human and Alzheimer's brain." Chauthaiwale V.M., Dhar M., McLachlan D.R., Joshi J.G. Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[8]	"Detection of ferritin heavy chain by SEREX: a multifunctional molecule in malignant tumour cells." Franco A.V., Gray C.P., Myers K., Hersey P. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[9]	"Identification of a human cell proliferation gene 15." Kim J.W. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon adenocarcinoma.
[11]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[12]	NHLBI resequencing and genotyping service (RS&G) Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[13]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Cervix, Colon, Lung, Ovary, Prostate and Salivary gland.
[15]	"Isolation and characterization of a cDNA clone for human ferritin heavy chain." Boyd D., Jain S.K., Crampton J., Barrett K.J., Drysdale J. Proc. Natl. Acad. Sci. U.S.A. 81:4751-4755(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 128-183.
[16]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[18]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179 AND SER-183, MASS SPECTROMETRY. Tissue: Liver.
[19]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, MASS SPECTROMETRY.
[22]	"Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts." Lawson D.M., Artymiuk P.J., Yewdall S.J., Smith J.M.A., Livingstone J.C., Treffry A., Luzzago A., Levi S., Arosio P., Cesarini G., Thomas C.D., Shaw W.V., Harrison P.M. Nature 349:541-544(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[23]	"Comparison of the three-dimensional structures of recombinant human H and horse L ferritins at high resolution." Hempstead P.D., Yewdall S.J., Fernie A.R., Lawson D.M., Artymiuk P.J., Rice D.W., Ford G.C., Harrison P.M. J. Mol. Biol. 268:424-448(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Wikipedia

Ferritin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00318 mRNA. Translation: CAA25086.1.
M11146 mRNA. Translation: AAA52437.1.
M12937 mRNA. Translation: AAA35830.1.
X03487, X03488 Genomic DNA. Translation: CAA27205.1.
M14212, M14211 Genomic DNA. Translation: AAA52438.1.
M97164 mRNA. Translation: AAA35832.1.
L20941 mRNA. Translation: AAA35833.1.
AF088851 mRNA. Translation: AAF89523.1.
AY258285 mRNA. Translation: AAP82230.1.
AB062402 mRNA. Translation: BAB93489.1.
AK054816 mRNA. Translation: BAG51427.1.
DQ496108 Genomic DNA. Translation: ABF47097.1.
CH471076 Genomic DNA. Translation: EAW73989.1.
BC000857 mRNA. Translation: AAH00857.1.
BC001399 mRNA. Translation: AAH01399.1.
BC011359 mRNA. Translation: AAH11359.1.
BC013724 mRNA. Translation: AAH13724.1.
BC015156 mRNA. Translation: AAH15156.1.
BC016009 mRNA. Translation: AAH16009.1.
BC016857 mRNA. Translation: AAH16857.1.
BC063514 mRNA. Translation: AAH63514.1.
BC066961 mRNA. Translation: AAH66961.1.
BC073750 mRNA. Translation: AAH73750.1.
BC104643 mRNA. Translation: AAI04644.1.
BC105802 mRNA. Translation: AAI05803.1. Different initiation.
M15383 mRNA. Translation: AAA52479.1.

IPI

IPI00554521.

PIR

FRHUH. A23517.

RefSeq

NP_002023.2. NM_002032.2.

UniGene

Hs.524910.
Hs.645560.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FHA	X-ray	2.40	A	1-183	[»]
2CEI	X-ray	1.80	A	2-182	[»]
2CHI	X-ray	1.60	A	2-182	[»]
2CIH	X-ray	1.50	A	2-182	[»]
2CLU	X-ray	2.10	A	2-182	[»]
2CN6	X-ray	2.20	A	2-182	[»]
2CN7	X-ray	1.75	A	2-182	[»]
2FHA	X-ray	1.90	A	1-183	[»]
2IU2	X-ray	1.80	A	2-182	[»]
2Z6M	X-ray	2.72	A/B/C/D/E/F/G/H/I/J/K/L	2-177	[»]
3AJO	X-ray	1.52	A	2-183	[»]
3AJP	X-ray	1.90	A	2-183	[»]
3AJQ	X-ray	1.58	A	2-183	[»]
3ERZ	X-ray	3.06	A/B/C/D/E/F/G/H/I/J/K/L	1-183	[»]
3ES3	X-ray	2.79	A	1-183	[»]
4DYX	X-ray	1.85	A	6-177	[»]
4DYY	X-ray	1.90	A	6-177	[»]
4DYZ	X-ray	2.30	A	6-177	[»]
4DZ0	X-ray	2.50	A	6-177	[»]

ProteinModelPortal

P02794.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38301N.

IntAct

P02794. 26 interactions.

MINT

MINT-4822446.

STRING

9606.ENSP00000273550.

PTM databases

PhosphoSite

P02794.

Polymorphism databases

DMDM

120516.

2D gel databases

UCD-2DPAGE

P02794.

Proteomic databases

PaxDb

P02794.

PRIDE

P02794.

Protocols and materials databases

DNASU

2495.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273550; ENSP00000273550; ENSG00000167996.

GeneID

2495.

KEGG

hsa:2495.

UCSC

uc001nsu.3. human.

Organism-specific databases

CTD

2495.

GeneCards

GC11M061731.

H-InvDB

HIX0128677.
HIX0200367.

HGNC

HGNC:3976. FTH1.

HPA

CAB008623.
HPA043650.

MIM

134770. gene+phenotype.

neXtProt

NX_P02794.

Orphanet

247790. FTH1-related iron overload.

PharmGKB

PA28392.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1528.

HOVERGEN

HBG000410.

InParanoid

P02794.

KO

K00522.

OrthoDB

EOG47PX78.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

P02794.

Bgee

P02794.

CleanEx

HS_FTH1.

Genevestigator

P02794.

GermOnline

ENSG00000167996. Homo sapiens.

Family and domain databases

Gene3D

1.20.1260.10. 1 hit.

InterPro

IPR001519. Ferritin.
IPR009040. Ferritin-like_diiron.
IPR009078. Ferritin-like_SF.
IPR012347. Ferritin-rel.
IPR014034. Ferritin_CS.
IPR008331. Ferritin_DPS_dom.
[Graphical view]

PANTHER

PTHR11431. PTHR11431. 1 hit.

Pfam

PF00210. Ferritin. 1 hit.
[Graphical view]

SUPFAM

SSF47240. Ferritin/RR_like. 1 hit.

PROSITE

PS00540. FERRITIN_1. 1 hit.
PS00204. FERRITIN_2. 1 hit.
PS50905. FERRITIN_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FTH1. human.

DrugBank

DB00893. Iron Dextran.

EvolutionaryTrace

P02794.

GenomeRNAi

2495.

NextBio

9857.

SOURCE

Search...

Entry information

Entry name

FRIH_HUMAN

Accession

Primary (citable) accession number: P02794
Secondary accession number(s): B3KNR5, Q3KRA8, Q3SWW1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 162 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.