P02792 (FRIL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ferritin light chain
Short name=Ferritin L subunit

Gene names

Name:

FTL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	175 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. 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. Ref.15 Ref.16
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. Iron enters the spherical protein shell through pores that are formed between subunits. Mutations leading to truncation or the addition of extra residues at the C-terminus interfere with normal pore formation and with iron accumulation. Ref.14 Ref.15 Ref.16
Involvement in disease	Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:600886]. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene. Ref.16 Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:606159]; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels. Ref.16 Ref.17
Sequence similarities	Belongs to the ferritin family. Contains 1 ferritin-like diiron domain.
Sequence caution	The sequence CAE11873.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Iron storage
Disease	Disease mutation Neurodegeneration
Ligand	Iron Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular iron ion homeostasis Traceable author statement. Source: ProtInc cellular membrane organization Traceable author statement. Source: Reactome iron ion transport Inferred from electronic annotation. Source: InterPro post-Golgi vesicle-mediated transport Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome intracellular ferritin complex Inferred from direct assay Ref.15Ref.16. Source: UniProtKB
Molecular function	ferric iron binding Inferred from electronic annotation. Source: InterPro identical protein binding Inferred from physical interaction. Source: IntAct oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		5	EBI-713279,EBI-713279

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.11

Chain

2 – 175

174

Ferritin light chain

PRO_0000201060

Regions

Domain

7 – 156

150

Ferritin-like diiron

Region

54 – 61

8

Catalytic site for iron oxidation

Sites

Metal binding

54

1

Iron

Metal binding

57

1

Iron

Metal binding

58

1

Iron

Metal binding

61

1

Iron

Metal binding

64

1

Iron

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.11

Modified residue

98

1

N6-acetyllysine Ref.13

Natural variations

Natural variant

96

1

A → T in NBIA3. Ref.17

VAR_026633

Experimental info

Sequence conflict

54

1

E → Q AA sequence Ref.11

Sequence conflict

87

1

E → Q AA sequence Ref.11

Sequence conflict

89

1

E → W AA sequence Ref.12

Sequence conflict

102

1

A → T in AAA35831. Ref.2

Sequence conflict

154

1

R → A AA sequence Ref.12

Sequence conflict

175

1

D → N AA sequence Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

175

Helix Strand Turn

Details...

Helix

11 – 37

27

Turn

41 – 43

3

Helix

46 – 72

27

Helix

93 – 120

28

Helix

124 – 133

10

Helix

135 – 154

20

Helix

160 – 170

11

Sequences

	Sequence		Length	Mass (Da)
	P02792 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 0DB98081FF976BC2	FASTA	175	20,020
	10 20 30 40 50 60 MSSQIRQNYS TDVEAAVNSL VNLYLQASYT YLSLGFYFDR DDVALEGVSH FFRELAEEKR 70 80 90 100 110 120 EGYERLLKMQ NQRGGRALFQ DIKKPAEDEW GKTPDAMKAA MALEKKLNQA LLDLHALGSA 130 140 150 160 170 RTDPHLCDFL ETHFLDEEVK LIKKMGDHLT NLHRLGGPEA GLGEYLFERL TLKHD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 3840162] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of human ferritin light subunit messenger RNA: comparison with heavy subunit message and functional implications." Dorner M.H., Salfeld J., Will H., Leibold E.A., Vass J.K., Munro H.N. Proc. Natl. Acad. Sci. U.S.A. 82:3139-3143(1985) [PubMed: 3858810] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of the gene coding for human L apoferritin." Santoro C., Marone M., Ferrone M., Costanzo F., Colombo M., Minganti C., Cortese R., Silengo L. Nucleic Acids Res. 14:2863-2876(1986) [PubMed: 3754330] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Expression of a ferritin-like mRNA by abdominal aortic aneurysm (AAA) adventitial fibroblasts." Jordan T.P., Li X.G., Bhatti A.F., Obunike J.C., Tilson M.D. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon endothelium.
[8]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Skin, Testis and Urinary bladder.
[10]	"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: 3023856] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-175.
[11]	"The amino acid sequence of human liver apoferritin." Addison J.M., Fitton J.E., Lewis W.G., May K., Harrison P.M. FEBS Lett. 164:139-144(1983) [PubMed: 6653779] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-36 AND 41-175. Tissue: Liver.
[12]	"Characterization of the human small-ribosomal-subunit proteins by N-terminal and internal sequencing, and mass spectrometry." Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K., Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A. Eur. J. Biochem. 239:144-149(1996) [PubMed: 8706699] [Abstract] Cited for: PROTEIN SEQUENCE OF 84-90 AND 145-155. Tissue: Placenta.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-98, MASS SPECTROMETRY.
[14]	"Structure of human ferritin L chain." Wang Z., Li C., Ellenburg M., Soistman E., Ruble J., Wright B., Ho J.X., Carter D.C. Acta Crystallogr. D 62:800-806(2006) [PubMed: 16790936] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-174, SUBUNIT.
[15]	"Unraveling of the E-helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration." Baraibar M.A., Muhoberac B.B., Garringer H.J., Hurley T.D., Vidal R. J. Biol. Chem. 285:1950-1956(2010) [PubMed: 19923220] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 1-191, FUNCTION, SUBUNIT, DOMAIN.
[16]	"Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation." Luscieti S., Santambrogio P., Langlois d'Estaintot B., Granier T., Cozzi A., Poli M., Gallois B., Finazzi D., Cattaneo A., Levi S., Arosio P. J. Biol. Chem. 285:11948-11957(2010) [PubMed: 20159981] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-166, FUNCTION, SUBUNIT, DOMAIN, FERROXIDASE ACTIVITY, MASS SPECTROMETRY, ROLE IN DISEASE.
[17]	"Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement." Maciel P., Cruz V.T., Constante M., Iniesta I., Costa M.C., Gallati S., Sousa N., Sequeiros J., Coutinho P., Santos M.M. Neurology 65:603-605(2005) [PubMed: 16116125] [Abstract] Cited for: VARIANT NBIA3 THR-96.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Ferritin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11147 mRNA. Translation: AAA52439.1.
M10119 mRNA. Translation: AAA35831.1.
M12938 mRNA. Translation: AAA52440.1.
AY207005 mRNA. Translation: AAO52739.1.
CR456715 mRNA. Translation: CAG32996.1.
AK311773 mRNA. Translation: BAG34716.1.
BX571748 mRNA. Translation: CAE11873.1. Different initiation.
AC026803 Genomic DNA. No translation available.
BC002991 mRNA. Translation: AAH02991.2.
BC004245 mRNA. Translation: AAH04245.1.
BC008439 mRNA. Translation: AAH08439.1.
BC013928 mRNA. Translation: AAH13928.1.
BC016715 mRNA. Translation: AAH16715.1.
BC016346 mRNA. Translation: AAH16346.1.
BC016354 mRNA. Translation: AAH16354.1.
BC018990 mRNA. Translation: AAH18990.1.
BC021670 mRNA. Translation: AAH21670.1.
BC058820 mRNA. Translation: AAH58820.1.
BC062708 mRNA. Translation: AAH62708.1.
X03742 Genomic DNA. Translation: CAA27382.1.
X03743 Genomic DNA. Translation: CAA27383.1.
X03743 Genomic DNA. Translation: CAA27384.1.

IPI

IPI01014563.

PIR

FRHUL. B23920.

RefSeq

NP_000137.2. NM_000146.3.

UniGene

Hs.433670.
Hs.728304.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FFX	X-ray	1.90	J	2-173	[»]
2FG4	X-ray	2.10	A	2-174	[»]
2FG8	X-ray	2.50	A/B/C/D/E/F/G/H	2-174	[»]
3HX2	X-ray	2.85	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t/u/v/w/x	1-175	[»]
3HX5	X-ray	2.85	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t/u/v/w/x	1-175	[»]
3HX7	X-ray	2.85	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t/u/v/w/x	1-175	[»]
3KXU	X-ray	1.85	A	1-166	[»]

ProteinModelPortal

P02792.

SMR

P02792. Positions 2-157.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31248N.

IntAct

P02792. 15 interactions.

MINT

MINT-1187221.

STRING

P02792.

PTM databases

PhosphoSite

P02792.

Polymorphism databases

DMDM

120523.

2D gel databases

Cornea-2DPAGE

P02792.

Proteomic databases

PRIDE

P02792.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331825; ENSP00000366525; ENSG00000087086.

GeneID

2512.

KEGG

hsa:2512.

UCSC

uc002plo.1. human.

Organism-specific databases

CTD

2512.

GeneCards

GC19P049468.

H-InvDB

HIX0015310.

HGNC

HGNC:3999. FTL.

HPA

CAB020769.

MIM

134790. gene.
600886. phenotype.
606159. phenotype.

neXtProt

NX_P02792.

Orphanet

254704. Genetic hyperferritinemia without iron overload.
163. Hereditary hyperferritinemia with congenital cataracts.
157846. Neuroferritinopathy.

PharmGKB

PA28412.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG000410.

InParanoid

P02792.

OMA

QDLQKPS.

OrthoDB

EOG47PX78.

PhylomeDB

P02792.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

P02792.

Bgee

P02792.

CleanEx

HS_FTL.

Genevestigator

P02792.

GermOnline

ENSG00000087086. Homo sapiens.

Family and domain databases

InterPro

IPR001519. Ferritin.
IPR009040. Ferritin-like.
IPR012347. Ferritin-rel.
IPR009078. Ferritin/RR-like.
IPR014034. Ferritin_CS.
IPR008331. Ferritin_DPS_dom.
[Graphical view]

Gene3D

G3DSA:1.20.1260.10. Ferritin_rel. 1 hit.

KO

K13625.

PANTHER

PTHR11431. Ferritin_N. 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

DrugBank

DB00893. Iron Dextran.

NextBio

9899.

SOURCE

Search...

Entry information

Entry name

FRIL_HUMAN

Accession

Primary (citable) accession number: P02792
Secondary accession number(s): B2R4B9 , Q6IBT7, Q7Z2W1, Q86WI9, Q8WU07, Q96AU9, Q96CU0, Q9BTZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 132 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.