Ferrochelatase, mitochondrial

Details

Name
Ferrochelatase, mitochondrial
Synonyms
  • 4.99.1.1
  • Heme synthase
  • Protoheme ferro-lyase
Gene Name
FECH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002057|Ferrochelatase, mitochondrial
MRSLGANMAAALRAAGVLLRDPLASSSWRVCQPWRWKSGAAAAAVTTETAQHAQGAKPQV
QPQKRKPKTGILMLNMGGPETLGDVHDFLLRLFLDRDLMTLPIQNKLAPFIAKRRTPKIQ
EQYRRIGGGSPIKIWTSKQGEGMVKLLDELSPNTAPHKYYIGFRYVHPLTEEAIEEMERD
GLERAIAFTQYPQYSCSTTGSSLNAIYRYYNQVGRKPTMKWSTIDRWPTHHLLIQCFADH
ILKELDHFPLEKRSEVVILFSAHSLPMSVVNRGDPYPQEVSATVQKVMERLEYCNPYRLV
WQSKVGPMPWLGPQTDESIKGLCERGRKNILLVPIAFTSDHIETLYELDIEYSQVLAKEC
GVENIRRAESLNGNPLFSKALADLVHSHIQSNELCSKQLTLSCPLCVNPVCRETKSFFTS
QQL
Number of residues
423
Molecular Weight
47861.77
Theoretical pI
8.91
GO Classification
Functions
2 iron, 2 sulfur cluster binding / ferrochelatase activity / ferrous iron binding / heme binding / iron-responsive element binding
Processes
cellular response to dexamethasone stimulus / cholesterol metabolic process / detection of UV / erythrocyte differentiation / generation of precursor metabolites and energy / heme biosynthetic process / iron ion homeostasis / porphyrin-containing compound metabolic process / protoporphyrinogen IX metabolic process / regulation of eIF2 alpha phosphorylation by heme / regulation of gene expression / regulation of hemoglobin biosynthetic process / response to arsenic-containing substance / response to drug / response to ethanol / response to insecticide / response to lead ion / response to light stimulus / response to methylmercury / response to platinum ion / small molecule metabolic process / very-low-density lipoprotein particle assembly
Components
mitochondrial inner membrane / mitochondrial matrix / mitochondrion
General Function
Iron-responsive element binding
Specific Function
Catalyzes the ferrous insertion into protoporphyrin IX.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0019053|Ferrochelatase, mitochondrial (FECH)
ATGCGTTCACTCGGCGCAAACATGGCTGCGGCCCTGCGCGCCGCGGGCGTCCTGCTCCGC
GATCCGCTGGCATCCAGCAGCTGGAGGGTCTGTCAGCCATGGAGGTGGAAGTCAGGTGCA
GCTGCAGCGGCCGTCACCACAGAAACAGCCCAGCATGCCCAGGGTGCAAAACCTCAAGTT
CAACCGCAGAAGAGGAAGCCGAAAACTGGAATATTAATGCTAAACATGGGAGGCCCTGAA
ACTCTTGGAGATGTTCACGACTTCCTTCTGAGACTCTTCTTGGACCGAGACCTCATGACA
CTTCCTATTCAGAATAAGCTGGCACCATTCATCGCCAAACGCCGAACCCCCAAGATTCAA
GAGCAGTACCGCAGGATTGGAGGCGGATCCCCCATCAAGATATGGACTTCCAAGCAGGGA
GAGGGCATGGTGAAGCTGCTGGATGAATTGTCCCCCAACACAGCCCCTCACAAATACTAT
ATTGGATTTCGGTACGTCCATCCTTTAACAGAAGAAGCAATTGAAGAGATGGAGAGAGAT
GGCCTAGAAAGGGCTATTGCTTTCACACAGTATCCACAGTACAGCTGCTCCACCACAGGC
AGCAGCTTAAATGCCATTTACAGATACTATAATCAAGTGGGACGGAAGCCCACGATGAAG
TGGAGCACTATTGACAGGTGGCCCACACATCACCTCCTCATCCAGTGCTTTGCAGATCAT
ATTCTAAAGGAACTGGACCATTTTCCACTTGAGAAGAGAAGCGAGGTGGTCATTCTGTTT
TCTGCTCACTCACTGCCCATGTCTGTGGTCAACAGAGGCGACCCATATCCTCAGGAGGTA
AGCGCCACTGTCCAAAAAGTCATGGAAAGGCTGGAGTACTGCAACCCCTACCGACTGGTG
TGGCAATCCAAGGTTGGTCCAATGCCCTGGTTGGGTCCTCAAACAGACGAATCTATCAAA
GGGCTTTGTGAGAGGGGGAGGAAGAATATCCTCTTGGTTCCGATAGCATTTACCAGTGAC
CATATTGAAACGCTGTATGAGCTGGACATCGAGTACTCTCAAGTTTTAGCCAAGGAGTGT
GGAGTTGAAAACATCAGAAGAGCTGAGTCTCTTAATGGAAATCCATTGTTCTCTAAGGCC
CTGGCCGACTTGGTGCATTCACACATCCAGTCAAACGAGCTGTGTTCCAAGCAGCTGACC
CTGAGCTGTCCGCTCTGTGTCAATCCTGTCTGCAGGGAGACTAAATCCTTCTTCACCAGC
CAGCAGCTGTGA
Chromosome Location
18
Locus
18q21.3
External Identifiers
ResourceLink
UniProtKB IDP22830
UniProtKB Entry NameHEMH_HUMAN
GenBank Protein ID219656
GenBank Gene IDD00726
GenAtlas IDFECH
HGNC IDHGNC:3647
General References
  1. 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. [Article]
  2. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  10. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  11. 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. [Article]
  12. Medlock A, Swartz L, Dailey TA, Dailey HA, Lanzilotta WN: Substrate interactions with human ferrochelatase. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1789-93. Epub 2007 Jan 29. [Article]
  13. Cox TM: Erythropoietic protoporphyria. J Inherit Metab Dis. 1997 Jun;20(2):258-69. [Article]
  14. 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. [Article]
  15. 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. [Article]
  16. Sarkany RP, Alexander GJ, Cox TM: Recessive inheritance of erythropoietic protoporphyria with liver failure. Lancet. 1994 Jun 4;343(8910):1394-6. [Article]
  17. 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. [Article]
  18. 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. [Article]
  19. 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. [Article]
  20. 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. [Article]
  21. 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. [Article]
  22. 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. [Article]
  23. 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. [Article]
  24. 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. [Article]
  25. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02659Cholic AcidapprovedunknownDetails