Escherichia coli K-12 substr. MG1655 Enzyme: ferrochelatase

Gene: hemH Accession Numbers: EG10431 (EcoCyc), b0475, ECK0469

Synonyms: popA, visA

Regulation Summary Diagram: ?

Regulation summary diagram for hemH

Ferrochelatase is the terminal enzyme in the heme biosynthesis pathway and catalyzes the insertion of Fe2+ into protoporphyrin IX.

Both eukaryotic and some microbial ferrochelatases have been shown to contain a [2Fe-2S] cluster [Dailey02]; however, no studies have been performed with the E. coli enzyme.

A hemH mutant is sensitive to visible light due to the accumulation of protoporphyrin IX. This is similar to the defect observed in human protoporphyria [Nakahigashi91, Miyamoto92]. The defect in iron incorporation into protoporphyrin IX in a hemH mutant results in a defect in assembly of membrane-associated succinate-ubiquinone reductase [Nihei01]. Expression of hemH is mildly regulated in response to heme availability [McNicholas97a] and is activated by OxyR [Zheng01].

VisA: "visible light-sensitive" [Miyamoto91]
HemH: "heme biosynthesis"

Reviews: [Dailey00, OBrian02]

Locations: cytosol

Map Position: [497,279 -> 498,241] (10.72 centisomes, 39°)
Length: 963 bp / 320 aa

Molecular Weight of Polypeptide: 35.884 kD (from nucleotide sequence), 35.0 kD (experimental) [Miyamoto94 ]

pI: 6.59

Unification Links: ASAP:ABE-0001649 , CGSC:641 , EchoBASE:EB0426 , EcoGene:EG10431 , EcoliWiki:b0475 , ModBase:P23871 , OU-Microarray:b0475 , PortEco:hemH , PR:PRO_000022876 , Protein Model Portal:P23871 , RefSeq:NP_415008 , RegulonDB:EG10431 , SMR:P23871 , String:511145.b0475 , UniProt:P23871

Relationship Links: InterPro:IN-FAMILY:IPR001015 , InterPro:IN-FAMILY:IPR019772 , Panther:IN-FAMILY:PTHR11108 , Pfam:IN-FAMILY:PF00762 , Prosite:IN-FAMILY:PS00534

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hemH

GO Terms:

Biological Process: GO:0006783 - heme biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Frustaci93, Nakahigashi91, McConville79]
GO:0009416 - response to light stimulus Inferred from experiment [Miyamoto91, Nakahigashi91]
GO:0046501 - protoporphyrinogen IX metabolic process Inferred from experiment [Miyamoto92]
GO:0006779 - porphyrin-containing compound biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004325 - ferrochelatase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Frustaci93, Miyamoto92, Miyamoto94]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers heme, porphyrine

Essentiality data for hemH knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Last-Curated ? 07-Jul-2009 by Keseler I , SRI International

Enzymatic reaction of: ferrochelatase

Synonyms: protoheme ferro-lyase, heme synthase

EC Number:

Fe2+ + protoporphyrin IX <=> ferroheme b + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

This reaction is reversible.

In Pathways: superpathway of heme biosynthesis from uroporphyrinogen-III , heme biosynthesis I (aerobic) , heme biosynthesis II (anaerobic)

pH(opt): 8.0 [BRENDA14, Miyamoto94]

Sequence Features

Protein sequence of ferrochelatase with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 54
[Miyamoto91, UniProt10a]
UniProt: (in Ref. 1; BAA14304);
Metal-Binding-Site 194
UniProt: Iron; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 275
UniProt: Iron; Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


3/2/1998 (pkarp) Merged genes G794/b0475 and EG10431/hemH
10/20/97 Gene b0475 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10431; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Dailey00: Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP, Wang BC (2000). "Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters." Cell Mol Life Sci 57(13-14);1909-26. PMID: 11215517

Dailey02: Dailey TA, Dailey HA (2002). "Identification of [2Fe-2S] clusters in microbial ferrochelatases." J Bacteriol 184(9);2460-4. PMID: 11948160

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Frustaci93: Frustaci JM, O'Brian MR (1993). "The Escherichia coli visA gene encodes ferrochelatase, the final enzyme of the heme biosynthetic pathway." J Bacteriol 175(7);2154-6. PMID: 8458858

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

McConville79: McConville ML, Charles HP (1979). "Isolation of haemin-requiring mutants of Escherichia coli K12." J Gen Microbiol 113(1);155-64. PMID: 387909

McNicholas97a: McNicholas PM, Javor G, Darie S, Gunsalus RP (1997). "Expression of the heme biosynthetic pathway genes hemCD, hemH, hemM, and hemA of Escherichia coli." FEMS Microbiol Lett 146(1);143-8. PMID: 8997718

Miyamoto91: Miyamoto K, Nakahigashi K, Nishimura K, Inokuchi H (1991). "Isolation and characterization of visible light-sensitive mutants of Escherichia coli K12." J Mol Biol 219(3);393-8. PMID: 2051480

Miyamoto92: Miyamoto K, Nishimura K, Masuda T, Tsuji H, Inokuchi H (1992). "Accumulation of protoporphyrin IX in light-sensitive mutants of Escherichia coli." FEBS Lett 310(3);246-8. PMID: 1397280

Miyamoto94: Miyamoto K, Kanaya S, Morikawa K, Inokuchi H (1994). "Overproduction, purification, and characterization of ferrochelatase from Escherichia coli." J Biochem 115(3);545-51. PMID: 8056770

Nakahigashi91: Nakahigashi K, Nishimura K, Miyamoto K, Inokuchi H (1991). "Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12." Proc Natl Acad Sci U S A 88(23);10520-4. PMID: 1835790

Nihei01: Nihei C, Nakayashiki T, Nakamura K, Inokuchi H, Gennis RB, Kojima S, Kita K (2001). "Abortive assembly of succinate-ubiquinone reductase (complex II) in a ferrochelatase-deficient mutant of Escherichia coli." Mol Genet Genomics 265(3);394-404. PMID: 11405622

OBrian02: O'Brian MR, Thony-Meyer L (2002). "Biochemistry, regulation and genomics of haem biosynthesis in prokaryotes." Adv Microb Physiol 46;257-318. PMID: 12073655

Porra72: Porra RJ, Langman L, Young IG, Gibson F (1972). "The role of ferric enterochelin esterase in enterochelin-mediated iron transport and ferrochelatase activity in Escherichia coli." Arch Biochem Biophys 153(1);74-8. PMID: 4568262

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zheng01: Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G (2001). "DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide." J Bacteriol 183(15);4562-70. PMID: 11443091

Other References Related to Gene Regulation

Li13: Li F, Wang Y, Gong K, Wang Q, Liang Q, Qi Q (2013). "Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli." FEMS Microbiol Lett. PMID: 24188714

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Sat Oct 10, 2015, biocyc13.