フェロケラターゼ
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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
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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
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Cellular component |
• mitochondrial inner membrane
• mitochondrial matrix
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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
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
2235 |
14151 |
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Ensembl |
ENSG00000066926 |
ENSMUSG00000024588 |
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UniProt |
P22830 |
P22315 |
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RefSeq (mRNA) |
NM_000140 |
NM_007998 |
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RefSeq (protein) |
NP_000131 |
NP_032024 |
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Location (UCSC) |
Chr 18:
55.22 – 55.25 Mb |
Chr 18:
64.46 – 64.49 Mb |
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PubMed search |
[1] |
[2] |
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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+.
Contents
- 1 Function
- 2 Structure
- 3 Clinical significance
- 4 Interactions
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
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 |
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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.[1]
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 |
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A ferrochelatase enzyme consists of 497 amino acid residues with a m.w. of 55.4 kDa.[1]
Clinical significance
Defects in ferrochelatase are associated with erythropoietic protoporphyria.[1]
Interactions
Ferrochelatase has been shown to interact with ABCB7.[2]
See also
- Lyases
- Erythropoietic protoporphyria
- Sirohydrochlorin ferrochelatase
References
- ^ a b c "Entrez Gene: FECH ferrochelatase (protoporphyria)".
- ^ Taketani S, Kakimoto K, Ueta H, Masaki R, Furukawa T (Apr 2003). "Involvement of ABC7 in the biosynthesis of heme in erythroid cells: interaction of ABC7 with ferrochelatase". Blood 101 (8): 3274–80. doi:10.1182/blood-2002-04-1212. PMID 12480705.
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)
PDB gallery
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1hrk: CRYSTAL STRUCTURE OF HUMAN FERROCHELATASE
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2hrc: 1.7 angstrom structure of human ferrochelatase variant R115L
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2hre: Structure of human ferrochelatase variant E343K with protoporphyrin IX bound
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Enzymes involved in the metabolism of heme and porphyrin
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Porphyrin biosynthesis |
early mitochondrial: |
- Aminolevulinic acid synthase
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cytosolic: |
- Porphobilinogen synthase
- Porphobilinogen deaminase
- Uroporphyrinogen III synthase
- Uroporphyrinogen III decarboxylase
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late mitochondrial: |
- Coproporphyrinogen III oxidase
- Protoporphyrinogen oxidase
- Ferrochelatase
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Heme degradation
to bile |
spleen: |
- Heme oxygenase
- Biliverdin reductase
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liver: |
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Index of cells from bone marrow
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Description |
- Immune system
- Cells
- Physiology
- coagulation
- proteins
- granule contents
- colony-stimulating
- heme and porphyrin
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Disease |
- Red blood cell
- Monocyte and granulocyte
- Neoplasms and cancer
- Histiocytosis
- Symptoms and signs
- Blood tests
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Treatment |
- Transfusion
- Drugs
- thrombosis
- bleeding
- other
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UpToDate Contents
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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
Related Links
- Buy Ferrochelatase antibodies from Santa Cruz. Select a Ferrochelatase antibody from 1 monoclonal and 5 polyclonal antibodies. si/shRNA products also available. ... HOVERcruz ,を紹介します。 a unique system for rapid ...
- 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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