Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015 (Sat)
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015 (Sat)
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015 (Sat)
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015 (Sat)
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015 (Sat)

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 [McNicholas97] 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 [UniProtGOA11, GOA06, GOA01, 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 [UniProtGOA11]
Molecular Function: GO:0004325 - ferrochelatase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Frustaci93, Miyamoto92, Miyamoto94]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, 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, UniProt10]
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, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

McNicholas97: 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 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms 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

Li13a: 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

Report Errors or Provide Feedback
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 Wed Sep 2, 2015, biocyc11.