Fech ferrochelatase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Fechprovided by MGI
Official Full Name: ferrochelataseprovided by MGI
Primary source: MGI:MGI:95513
See related: Ensembl:ENSMUSG00000024588 AllianceGenome:MGI:95513
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Fcl; fch
Summary: Enables several functions, including ferrochelatase activity; heme binding activity; and iron-responsive element binding activity. Involved in heme A biosynthetic process; heme B biosynthetic process; and heme O biosynthetic process. Acts upstream of or within several processes, including multicellular organismal-level iron ion homeostasis; regulation of protein metabolic process; and very-low-density lipoprotein particle assembly. Located in mitochondrial inner membrane. Is active in mitochondrial matrix. Is expressed in several structures, including choroid plexus; heart; integumental system; liver and biliary system; and respiratory system. Used to study erythropoietic protoporphyria. Human ortholog(s) of this gene implicated in cutaneous porphyria and erythropoietic protoporphyria. Orthologous to human FECH (ferrochelatase). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in liver E14.5 (RPKM 171.3), liver E14 (RPKM 167.9) and 18 other tissues See more
Orthologs: human all
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Genomic context

Location:: 18 E1; 18 37.43 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	18	NC_000084.7 (64589613..64622169, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	18	NC_000084.6 (64456542..64489098, complement)

Chromosome 18 - NC_000084.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ferrochelatase regulates retinal neovascularization.
Title: Ferrochelatase regulates retinal neovascularization.
FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity
Title: FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity.
5-aza-2'-deoxycytidine activates iron uptake and heme biosynthesis by increasing c-Myc nuclear localization and binding to the E-boxes of transferrin receptor 1 (TfR1) and ferrochelatase (Fech) genes.
Title: 5-aza-2'-deoxycytidine activates iron uptake and heme biosynthesis by increasing c-Myc nuclear localization and binding to the E-boxes of transferrin receptor 1 (TfR1) and ferrochelatase (Fech) genes.
analysis of the inhibitory metal ion-binding site in ferrochelatase
Title: Identification and characterization of an inhibitory metal ion-binding site in ferrochelatase.
Fech forms an oligomeric complex with Mfrn1 and Abcb10 to synergistically integrate mitochondrial iron importation and use for heme biosynthesis.
Title: Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis.
Ferrochelatase activity and protein levels were dramatically decreased in Irp2(-/-) spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo
Title: Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery.
analysis of skin ferrochelatase and photosensitivity in mice and man
Title: Skin ferrochelatase and photosensitivity in mice and man.
3-D structural models are presented (for wild-type and mutant expressed forms); binding of porphyrin (primary product) is studied using simulation models; amino acid sequence and alignment with 5 other ferrochelatase sequences are presented
Title: Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?
ferrochelatase localizes to both the mitochondrial outer and inner membranes, and the change in the equilibrium position of the forward and reverse activities may be regulated by the phosphorylation of ferrochelatase
Title: Dual mitochondrial localization and different roles of the reversible reaction of mammalian ferrochelatase.
These results provide new insights into the role of the active site residues of ferrochelatase in controlling stereospecificity, distortion and metallation.
Title: Porphyrin binding and distortion and substrate specificity in the ferrochelatase reaction: the role of active site residues.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (3)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

M61215 (e-PCR)
- UniSTS:124963

AI894116 (e-PCR)
- UniSTS:181135

MHAa30f10.seq (e-PCR)
- UniSTS:125124

D18Mit206 (e-PCR), detects polymorphism
- UniSTS:128224

M61215 (e-PCR)
- UniSTS:160753

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables ferrochelatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ferrochelatase activity	IDA Inferred from Direct Assay more info	PubMed
enables ferrochelatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ferrochelatase activity	ISO Inferred from Sequence Orthology more info	PubMed
enables heme binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables iron ion binding	IDA Inferred from Direct Assay more info	PubMed
enables iron-responsive element binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables tetrapyrrole binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to dexamethasone stimulus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cholesterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within detection of UV	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within erythrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme A biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme B biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme O biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within heme biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within heme biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within heme biosynthetic process	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within multicellular organismal-level iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within porphyrin-containing compound biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protoporphyrinogen IX metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protoporphyrinogen IX metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of eIF2 alpha phosphorylation by heme	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of eIF2 alpha phosphorylation by heme	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of hemoglobin biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to arsenic-containing substance	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to insecticide	IEA Inferred from Electronic Annotation more info
involved_in response to lead ion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to light stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to methylmercury	IEA Inferred from Electronic Annotation more info
involved_in response to platinum ion	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within very-low-density lipoprotein particle assembly	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info	PubMed
is_active_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: ferrochelatase, mitochondrial

Names: heme synthase; heme synthetase; protoheme ferro-lyase

NP_001334984.1

EC 4.98.1.1

NP_032024.2

EC 4.98.1.1

XP_036016877.1

EC 4.98.1.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001348055.2 → NP_001334984.1 ferrochelatase, mitochondrial isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks an in-frame portion of the 5' coding region, and uses a downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC102106, AC102268, AEKQ02072540

UniProtKB/TrEMBL

F6T2S0

Related

ENSMUSP00000025484.9, ENSMUST00000025484.9

Conserved Domains (1) summary

pfam00762
Location:1 → 317

Ferrochelatase
NM_007998.8 → NP_032024.2 ferrochelatase, mitochondrial isoform 1

See identical proteins and their annotated locations for NP_032024.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC102106, AC102268, AEKQ02072540

Consensus CDS

CCDS29303.1

UniProtKB/Swiss-Prot

P22315, Q544X6

UniProtKB/TrEMBL

Q3UC49

Related

ENSMUSP00000157791.2, ENSMUST00000236586.3

Conserved Domains (3) summary

cd00419
Location:234 → 371

Ferrochelatase_C; Ferrochelatase, C-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...

cd03411
Location:68 → 229

Ferrochelatase_N; Ferrochelatase, N-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...

pfam00762
Location:68 → 388

Ferrochelatase; Ferrochelatase

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000084.7 Reference GRCm39 C57BL/6J

Range

64589613..64622169 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036160984.1 → XP_036016877.1 ferrochelatase, mitochondrial isoform X1

UniProtKB/TrEMBL

F6T2S0

Conserved Domains (1) summary

pfam00762
Location:1 → 317

Ferrochelatase