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Identification
HMDB Protein ID HMDBP01058
Secondary Accession Numbers
  • 6347
  • HMDBP07020
Name Ferrochelatase, mitochondrial
Synonyms
  1. Heme synthase
  2. Protoheme ferro-lyase
Gene Name FECH
Protein Type Unknown
Biological Properties
General Function Involved in ferrochelatase activity
Specific Function Catalyzes the ferrous insertion into protoporphyrin IX.
Pathways
  • Acute Intermittent Porphyria
  • Congenital Erythropoietic Porphyria (CEP) or Gunther Disease
  • Hereditary Coproporphyria (HCP)
  • Porphyria Variegata (PV)
  • Porphyrin and chlorophyll metabolism
  • Porphyrin Metabolism
  • protoheme biosynthesis
Reactions
Heme + Hydrogen Ion → Protoporphyrin IX + Fe2+ details
Protoporphyrin IX + Fe2+ → Heme + Hydrogen Ion details
GO Classification
Biological Process
small molecule metabolic process
response to arsenic-containing substance
heme biosynthetic process
response to light stimulus
response to insecticide
iron ion homeostasis
cholesterol metabolic process
response to drug
response to ethanol
generation of precursor metabolites and energy
erythrocyte differentiation
very-low-density lipoprotein particle assembly
detection of UV
protoporphyrinogen IX metabolic process
regulation of eIF2 alpha phosphorylation by heme
regulation of hemoglobin biosynthetic process
response to platinum ion
response to lead ion
cellular response to dexamethasone stimulus
response to methylmercury
Cellular Component
mitochondrial matrix
mitochondrial inner membrane
Function
catalytic activity
lyase activity
ferrochelatase activity
Molecular Function
ferrous iron binding
2 iron, 2 sulfur cluster binding
iron-responsive element binding
heme binding
ferrochelatase activity
Process
metabolic process
nitrogen compound metabolic process
tetrapyrrole metabolic process
porphyrin metabolic process
heme biosynthetic process
porphyrin biosynthetic process
Cellular Location
  1. Peripheral membrane protein
  2. Mitochondrion inner membrane
  3. Matrix side
Gene Properties
Chromosome Location 18
Locus 18q21.3
SNPs FECH
Gene Sequence
>1272 bp
ATGCGTTCACTCGGCGCAAACATGGCTGCGGCCCTGCGCGCCGCGGGCGTCCTGCTCCGC
GATCCGCTGGCATCCAGCAGCTGGAGGGTCTGTCAGCCATGGAGGTGGAAGTCAGGTGCA
GCTGCAGCGGCCGTCACCACAGAAACAGCCCAGCATGCCCAGGGTGCAAAACCTCAAGTT
CAACCGCAGAAGAGGAAGCCGAAAACTGGAATATTAATGCTAAACATGGGAGGCCCTGAA
ACTCTTGGAGATGTTCACGACTTCCTTCTGAGACTCTTCTTGGACCGAGACCTCATGACA
CTTCCTATTCAGAATAAGCTGGCACCATTCATCGCCAAACGCCGAACCCCCAAGATTCAA
GAGCAGTACCGCAGGATTGGAGGCGGATCCCCCATCAAGATATGGACTTCCAAGCAGGGA
GAGGGCATGGTGAAGCTGCTGGATGAATTGTCCCCCAACACAGCCCCTCACAAATACTAT
ATTGGATTTCGGTACGTCCATCCTTTAACAGAAGAAGCAATTGAAGAGATGGAGAGAGAT
GGCCTAGAAAGGGCTATTGCTTTCACACAGTATCCACAGTACAGCTGCTCCACCACAGGC
AGCAGCTTAAATGCCATTTACAGATACTATAATCAAGTGGGACGGAAGCCCACGATGAAG
TGGAGCACTATTGACAGGTGGCCCACACATCACCTCCTCATCCAGTGCTTTGCAGATCAT
ATTCTAAAGGAACTGGACCATTTTCCACTTGAGAAGAGAAGCGAGGTGGTCATTCTGTTT
TCTGCTCACTCACTGCCCATGTCTGTGGTCAACAGAGGCGACCCATATCCTCAGGAGGTA
AGCGCCACTGTCCAAAAAGTCATGGAAAGGCTGGAGTACTGCAACCCCTACCGACTGGTG
TGGCAATCCAAGGTTGGTCCAATGCCCTGGTTGGGTCCTCAAACAGACGAATCTATCAAA
GGGCTTTGTGAGAGGGGGAGGAAGAATATCCTCTTGGTTCCGATAGCATTTACCAGTGAC
CATATTGAAACGCTGTATGAGCTGGACATCGAGTACTCTCAAGTTTTAGCCAAGGAGTGT
GGAGTTGAAAACATCAGAAGAGCTGAGTCTCTTAATGGAAATCCATTGTTCTCTAAGGCC
CTGGCCGACTTGGTGCATTCACACATCCAGTCAAACGAGCTGTGTTCCAAGCAGCTGACC
CTGAGCTGTCCGCTCTGTGTCAATCCTGTCTGCAGGGAGACTAAATCCTTCTTCACCAGC
CAGCAGCTGTGA
Protein Properties
Number of Residues 423
Molecular Weight 47861.77
Theoretical pI 8.728
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Ferrochelatase, mitochondrial
MRSLGANMAAALRAAGVLLRDPLASSSWRVCQPWRWKSGAAAAAVTTETAQHAQGAKPQV
QPQKRKPKTGILMLNMGGPETLGDVHDFLLRLFLDRDLMTLPIQNKLAPFIAKRRTPKIQ
EQYRRIGGGSPIKIWTSKQGEGMVKLLDELSPNTAPHKYYIGFRYVHPLTEEAIEEMERD
GLERAIAFTQYPQYSCSTTGSSLNAIYRYYNQVGRKPTMKWSTIDRWPTHHLLIQCFADH
ILKELDHFPLEKRSEVVILFSAHSLPMSVVNRGDPYPQEVSATVQKVMERLEYCNPYRLV
WQSKVGPMPWLGPQTDESIKGLCERGRKNILLVPIAFTSDHIETLYELDIEYSQVLAKEC
GVENIRRAESLNGNPLFSKALADLVHSHIQSNELCSKQLTLSCPLCVNPVCRETKSFFTS
QQL
GenBank ID Protein 60499021
UniProtKB/Swiss-Prot ID P22830
UniProtKB/Swiss-Prot Entry Name HEMH_HUMAN
PDB IDs
GenBank Gene ID NM_000140.3
GeneCard ID FECH
GenAtlas ID FECH
HGNC ID HGNC:3647
References
General References
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  3. Nakahashi Y, Taketani S, Okuda M, Inoue K, Tokunaga R: Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase. Biochem Biophys Res Commun. 1990 Dec 14;173(2):748-55. [PubMed:2260980 ]
  4. Tugores A, Magness ST, Brenner DA: A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene. J Biol Chem. 1994 Dec 9;269(49):30789-97. [PubMed:7983009 ]
  5. Dailey HA, Sellers VM, Dailey TA: Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases. J Biol Chem. 1994 Jan 7;269(1):390-5. [PubMed:8276824 ]
  6. Crouse BR, Sellers VM, Finnegan MG, Dailey HA, Johnson MK: Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster. Biochemistry. 1996 Dec 17;35(50):16222-9. [PubMed:8973195 ]
  7. Sellers VM, Wang KF, Johnson MK, Dailey HA: Evidence that the fourth ligand to the [2Fe-2S] cluster in animal ferrochelatase is a cysteine. Characterization of the enzyme from Drosophila melanogaster. J Biol Chem. 1998 Aug 28;273(35):22311-6. [PubMed:9712849 ]
  8. Wu CK, Dailey HA, Rose JP, Burden A, Sellers VM, Wang BC: The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol. 2001 Feb;8(2):156-60. [PubMed:11175906 ]
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  10. Lamoril J, Boulechfar S, de Verneuil H, Grandchamp B, Nordmann Y, Deybach JC: Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene. Biochem Biophys Res Commun. 1991 Dec 16;181(2):594-9. [PubMed:1755842 ]
  11. Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA: A molecular defect in human protoporphyria. Am J Hum Genet. 1992 Jun;50(6):1203-10. [PubMed:1376018 ]
  12. Sarkany RP, Alexander GJ, Cox TM: Recessive inheritance of erythropoietic protoporphyria with liver failure. Lancet. 1994 Jun 4;343(8910):1394-6. [PubMed:7910885 ]
  13. Imoto S, Tanizawa Y, Sato Y, Kaku K, Oka Y: A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria. Br J Haematol. 1996 Jul;94(1):191-7. [PubMed:8757534 ]
  14. Rufenacht UB, Gouya L, Schneider-Yin X, Puy H, Schafer BW, Aquaron R, Nordmann Y, Minder EI, Deybach JC: Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet. 1998 Jun;62(6):1341-52. [PubMed:9585598 ]
  15. Gouya L, Schneider-Yin X, Rufenacht U, Herrero C, Lecha M, Mascaro JM, Puy H, Deybach JC, Minder EI: Mutations in the ferrochelatase gene of four Spanish patients with erythropoietic protoporphyria. J Invest Dermatol. 1998 Sep;111(3):406-9. [PubMed:9740232 ]
  16. Schneider-Yin X, Gouya L, Dorsey M, Rufenacht U, Deybach JC, Ferreira GC: Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria. Blood. 2000 Aug 15;96(4):1545-9. [PubMed:10942404 ]
  17. Rufenacht UB, Gregor A, Gouya L, Tarczynska-Nosal S, Schneider-Yin X, Deybach JC: New missense mutation in the human ferrochelatase gene in a family with erythropoietic protoporphyria: functional studies and correlation of genotype and phenotype. Clin Chem. 2001 Jun;47(6):1112-3. [PubMed:11375302 ]
  18. Poh-Fitzpatrick MB, Wang X, Anderson KE, Bloomer JR, Bolwell B, Lichtin AE: Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations. J Am Acad Dermatol. 2002 Jun;46(6):861-6. [PubMed:12063482 ]
  19. Wiman A, Floderus Y, Harper P: Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria. J Hum Genet. 2003;48(2):70-6. [PubMed:12601550 ]
  20. Whatley SD, Mason NG, Khan M, Zamiri M, Badminton MN, Missaoui WN, Dailey TA, Dailey HA, Douglas WS, Wainwright NJ, Elder GH: Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease. J Med Genet. 2004 Aug;41(8):e105. [PubMed:15286165 ]
  21. Aurizi C, Schneider-Yin X, Sorge F, Macri A, Minder EI, Biolcati G: Heterogeneity of mutations in the ferrochelatase gene in Italian patients with erythropoietic protoporphyria. Mol Genet Metab. 2007 Apr;90(4):402-7. Epub 2006 Dec 29. [PubMed:17196862 ]