ferrochelatase

フェロケラターゼ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/07 18:49:41」(JST)

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Ferrochelatase
PDB rendering based on 1hrk.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HRK, 2HRC, 2HRE, 2PNJ, 2PO5, 2PO7, 2QD1, 2QD2, 2QD3, 2QD4, 2QD5, 3AQI, 3HCN, 3HCO, 3HCP, 3HCR, 3W1W, 4F4D, 4KLA, 4KMM, 4MK4
Identifiers
Symbols	FECH ; EPP; FCE
External IDs	OMIM: 612386 MGI: 95513 HomoloGene: 113 GeneCards: FECH Gene
EC number	4.99.1.1
Gene ontology Molecular function • ferrochelatase activity • protein binding • ferrous iron binding • heme binding • iron-responsive element binding • 2 iron, 2 sulfur cluster binding Cellular component • mitochondrial inner membrane • mitochondrial matrix Biological process • generation of precursor metabolites and energy • porphyrin-containing compound metabolic process • heme biosynthetic process • cholesterol metabolic process • response to light stimulus • detection of UV • response to lead ion • regulation of eIF2 alpha phosphorylation by heme • response to insecticide • erythrocyte differentiation • very-low-density lipoprotein particle assembly • response to drug • small molecule metabolic process • response to ethanol • protoporphyrinogen IX metabolic process • response to arsenic-containing substance • regulation of hemoglobin biosynthetic process • response to methylmercury • iron ion homeostasis • response to platinum ion • cellular response to dexamethasone stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2235	14151
Ensembl	ENSG00000066926	ENSMUSG00000024588
UniProt	P22830	P22315
RefSeq (mRNA)	NM_000140	NM_007998
RefSeq (protein)	NP_000131	NP_032024
Location (UCSC)	Chr 18: 55.22 – 55.25 Mb	Chr 18: 64.46 – 64.49 Mb
PubMed search	[1]	[2]

Ferrochelatase (FECH, protoheme ferrolyase) is an enzyme that catalyses the terminal (eighth) step in the biosynthesis of heme, converting protoporphyrin IX into heme. It catalyses the reaction:

protoporphyrin + Fe⁺⁺ ↔ protoheme + 2 H⁺.

Function

Ferrochelatase
Identifiers
EC number	4.99.1.1
CAS number	9012-93-5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Ferrochelatase is localized to the mitochondrion where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Two transcript variants encoding different isoforms have been found for this gene.

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Structure

Ferrochelatase
Identifiers
Symbol	Ferrochelatase
Pfam	PF00762
InterPro	IPR001015
PROSITE	PDOC00462
SCOP	1ak1
SUPERFAMILY	1ak1
OPM superfamily	137
OPM protein	1hrk
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

A ferrochelatase enzyme consists of 497 amino acid residues with a m.w. of 55.4 kDa.

Clinical significance

Defects in ferrochelatase are associated with erythropoietic protoporphyria.

Interactions

Ferrochelatase has been shown to interact with ABCB7.

See also

• Lyases
• Erythropoietic protoporphyria
• Sirohydrochlorin ferrochelatase

References

Further reading

• Cox TM (Jun 1997). "Erythropoietic protoporphyria". Journal of Inherited Metabolic Disease 20 (2): 258–69. doi:10.1023/A:1005317124985. PMID 9211198. 
• Buller RE, Schrader WT, O'Maller BW (May 1976). "Steroids and the practical aspects of performing binding studies". Journal of Steroid Biochemistry 7 (5): 321–6. doi:10.1016/0022-4731(76)90090-X. PMID 180343. 
• Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (Nov 1975). "Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts". The Journal of Clinical Investigation 56 (5): 1139–48. doi:10.1172/JCI108189. PMC 301976. PMID 1184741. 
• Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA (Jun 1992). "A molecular defect in human protoporphyria". American Journal of Human Genetics 50 (6): 1203–10. PMC 1682545. PMID 1376018. 
• Nakahashi Y, Fujita H, Taketani S, Ishida N, Kappas A, Sassa S (Jan 1992). "The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria". Proceedings of the National Academy of Sciences of the United States of America 89 (1): 281–5. doi:10.1073/pnas.89.1.281. PMC 48220. PMID 1729699. 
• Lamoril J, Boulechfar S, de Verneuil H, Grandchamp B, Nordmann Y, Deybach JC (Dec 1991). "Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene". Biochemical and Biophysical Research Communications 181 (2): 594–9. doi:10.1016/0006-291X(91)91231-Z. PMID 1755842. 
• Diep A, Li C, Klisak I, Mohandas T, Sparkes RS, Gaynor R et al. (Dec 1991). "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32". Genomics 11 (4): 1161–3. doi:10.1016/0888-7543(91)90047-I. PMID 1838349. 
• Nakahashi Y, Taketani S, Okuda M, Inoue K, Tokunaga R (Dec 1990). "Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase". Biochemical and Biophysical Research Communications 173 (2): 748–55. doi:10.1016/S0006-291X(05)80099-3. PMID 2260980. 
• Rossi E, Attwood PV, Garcia-Webb P, Costin KA (May 1990). "Inhibition of human lymphocyte ferrochelatase activity by hemin". Biochimica Et Biophysica Acta 1038 (3): 375–81. doi:10.1016/0167-4838(90)90251-A. PMID 2340297. 
• Polson RJ, Lim CK, Rolles K, Calne RY, Williams R (Sep 1988). "The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria". Transplantation 46 (3): 386–9. doi:10.1097/00007890-198809000-00010. PMID 3047929. 
• Bonkovsky HL, Schned AR (Jan 1986). "Fatal liver failure in protoporphyria. Synergism between ethanol excess and the genetic defect". Gastroenterology 90 (1): 191–201. PMID 3940245. 
• Prasad AR, Dailey HA (Aug 1995). "Effect of cellular location on the function of ferrochelatase". The Journal of Biological Chemistry 270 (31): 18198–200. doi:10.1074/jbc.270.31.18198. PMID 7629135. 
• Sarkany RP, Alexander GJ, Cox TM (Jun 1994). "Recessive inheritance of erythropoietic protoporphyria with liver failure". Lancet 343 (8910): 1394–6. doi:10.1016/S0140-6736(94)92525-9. PMID 7910885. 
• Tugores A, Magness ST, Brenner DA (Dec 1994). "A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene". The Journal of Biological Chemistry 269 (49): 30789–97. PMID 7983009. 
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Dailey HA, Sellers VM, Dailey TA (Jan 1994). "Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases". The Journal of Biological Chemistry 269 (1): 390–5. PMID 8276824. 
• Wang X, Poh-Fitzpatrick M, Carriero D, Ostasiewicz L, Chen T, Taketani S et al. (Apr 1993). "A novel mutation in erythropoietic protoporphyria: an aberrant ferrochelatase mRNA caused by exon skipping during RNA splicing". Biochimica Et Biophysica Acta 1181 (2): 198–200. doi:10.1016/0925-4439(93)90112-e. PMID 8481408. 
• Nakahashi Y, Miyazaki H, Kadota Y, Naitoh Y, Inoue K, Yamamoto M et al. (May 1993). "Molecular defect in human erythropoietic protoporphyria with fatal liver failure". Human Genetics 91 (4): 303–6. doi:10.1007/BF00217346. PMID 8500787. 
• Imoto S, Tanizawa Y, Sato Y, Kaku K, Oka Y (Jul 1996). "A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria". British Journal of Haematology 94 (1): 191–7. doi:10.1046/j.1365-2141.1996.d01-1771.x. PMID 8757534. 
• Crouse BR, Sellers VM, Finnegan MG, Dailey HA, Johnson MK (Dec 1996). "Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster". Biochemistry 35 (50): 16222–9. doi:10.1021/bi9620114. PMID 8973195. 

External links

• UMich Orientation of Proteins in Membranes protein/pdbid-1hrk
• Ferrochelatase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 骨髄性プロトポルフィリン症 erythropoietic protoporphyria
• 2. 先天性および後天性鉄芽球性貧血の原因 causes of congenital and acquired sideroblastic anemias
• 3. 鉄芽球性貧血の臨床的側面、診断、および治療 clinical aspects diagnosis and treatment of the sideroblastic anemias
• 4. 小児期の鉛中毒：臨床症状および診断 childhood lead poisoning clinical manifestations and diagnosis
• 5. バレット食道のアブレーションのための光線力学療法 photodynamic therapy for ablation of barretts esophagus

English Journal

• X-linked dominant protoporphyria: The first reported Japanese case.

• Ninomiya Y1, Kokunai Y1, Tanizaki H1, Akasaka E2, Nakano H2, Moriwaki S1.
• The Journal of dermatology.J Dermatol.2015 Sep 21. doi: 10.1111/1346-8138.13101. [Epub ahead of print]
• A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin
• PMID 26387792

• A metabolomic perspective of griseofulvin-induced liver injury in mice.

• Liu K1, Yan J1, Sachar M1, Zhang X2, Guan M2, Xie W1, Ma X3.
• Biochemical pharmacology.Biochem Pharmacol.2015 Sep 5. pii: S0006-2952(15)00575-4. doi: 10.1016/j.bcp.2015.09.002. [Epub ahead of print]
• Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in s
• PMID 26343413

• Kinetic Evaluation of Determinant Factors for Cellular Accumulation of Protoporphyrin IX Induced by External 5-Aminolevulinic Acid for Photodynamic Cancer Therapy.

• Nakanishi T1, Ogawa T1, Yanagihara C1, Tamai I1.
• Journal of pharmaceutical sciences.J Pharm Sci.2015 Sep;104(9):3092-100. doi: 10.1002/jps.24462. Epub 2015 May 8.
• Five-aminolevulinic acid (ALA) is a prodrug to generate phototoxic protoporphyrin IX (PPIX) for photodynamic cancer therapy. It remains unclear how PPIX accumulates in cancer cells; therefore, we aimed to clarify determinant factors by assessing ALA uptake, PPIX biosynthesis, conversion of PPIX to h
• PMID 25959076

Japanese Journal

• Improvement of the Efficacy of 5-aminolevulinic Acid-mediated Photodynamic Treatment in Human Oral Squamous Cell Carcinoma HSC-4

• Yamamoto Masanao,Fujita Hirofumi,Katase Naoki,Inoue Keiji,Nagatsuka Hitoshi,Utsumi Kozo,Sasaki Junzo,Ohuchi Hideyo
• Acta Medica Okayama 67(3), 153-164, 2013-06-00
• … Ferrochelatase (FECH) and ATP-binding cassette transporter G2 (ABCG2) are known to regulate PpIX accumulation. …
• NAID 120005295913

• Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation

• Kobuchi Hirotsugu,Moriya Koko,Ogino Tetsuya,Fujita Hirofumi,Inoue Keiji,Shuin Taro,Yasuda Tatsuji,Utsumi Kozo,Utsumi Toshihiko
• PLoS ONE 7(11), 2012-11-26
• … We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. …
• NAID 120005323823

• 症例 フェロケラターゼ遺伝子解析により診断した骨髄性プロトポルフィリン症

• 古市 恵,牧野 輝彦,松永 憲治 [他]
• 皮膚科の臨床 53(7), 1043-1046, 2011-07-00
• NAID 40018909240

Related Links

• Ferrochelatase 抗体 / Ferrochelatase 抗体 | サンタクルーズ ...

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• Ferrochelatase (h): 293T Lysate | Santa Cruz Biotech

100 µg protein in 200 µl SDS-PAGE buffer; suitable as Western Blotting control for Ferrochelatase antibodies human Ferrochelatase transfected 293T lysate suitable control antibody: Ferrochelatase (C-20): sc-49663 should be stored ...

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