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P22315 (HEMH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ferrochelatase, mitochondrial

EC=4.99.1.1
Alternative name(s):
Heme synthase
Protoheme ferro-lyase
Gene names
Name:Fech
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the ferrous insertion into protoporphyrin IX. HAMAP-Rule MF_00323

Catalytic activity

Protoheme + 2 H+ = protoporphyrin + Fe2+. HAMAP-Rule MF_00323

Cofactor

Binds 1 2Fe-2S cluster.

Enzyme regulation

Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor By similarity. HAMAP-Rule MF_00323

Pathway

Porphyrin-containing compound metabolism; protoheme biosynthesis; protoheme from protoporphyrin-IX: step 1/1. HAMAP-Rule MF_00323

Subunit structure

Monomer By similarity. HAMAP-Rule MF_00323

Subcellular location

Mitochondrion inner membrane; Peripheral membrane protein; Matrix side HAMAP-Rule MF_00323.

Tissue specificity

Erythroid and hepatic cells.

Induction

During erythroid differentiation. HAMAP-Rule MF_00323

Involvement in disease

Defects in Fech are the cause of a viable autosomal recessive mutation (named Fechm1Pas or Fch) that causes jaundice and anemia.

Sequence similarities

Belongs to the ferrochelatase family.

Sequence caution

The sequence AAA37615.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processHeme biosynthesis
Porphyrin biosynthesis
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   DiseaseDisease mutation
   DomainTransit peptide
   Ligand2Fe-2S
Iron
Iron-sulfur
Metal-binding
   Molecular functionLyase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to dexamethasone stimulus

Inferred from electronic annotation. Source: Ensembl

cholesterol metabolic process

Inferred from mutant phenotype PubMed 11160364. Source: MGI

detection of UV

Inferred from mutant phenotype PubMed 12149233. Source: MGI

erythrocyte differentiation

Inferred from mutant phenotype PubMed 1939658. Source: MGI

heme biosynthetic process

Inferred from direct assay PubMed 15496139PubMed 16503645. Source: MGI

iron ion homeostasis

Inferred from mutant phenotype PubMed 17003376. Source: MGI

porphyrin-containing compound biosynthetic process

Inferred from mutant phenotype PubMed 12149233. Source: MGI

protoporphyrinogen IX metabolic process

Inferred from genetic interaction PubMed 15931390. Source: MGI

regulation of eIF2 alpha phosphorylation by heme

Inferred from mutant phenotype PubMed 15931390. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 23395172. Source: MGI

regulation of hemoglobin biosynthetic process

Inferred from genetic interaction PubMed 15931390. Source: MGI

response to arsenic-containing substance

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to insecticide

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from electronic annotation. Source: Ensembl

response to light stimulus

Inferred from mutant phenotype PubMed 1939658. Source: MGI

response to methylmercury

Inferred from electronic annotation. Source: Ensembl

response to platinum ion

Inferred from electronic annotation. Source: Ensembl

very-low-density lipoprotein particle assembly

Inferred from mutant phenotype PubMed 11160364. Source: MGI

   Cellular_componentmitochondrial inner membrane

Traceable author statement PubMed 12149233. Source: MGI

mitochondrion

Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI

   Molecular_function2 iron, 2 sulfur cluster binding

Inferred from electronic annotation. Source: UniProtKB-KW

ferrochelatase activity

Inferred from direct assay PubMed 12149233PubMed 14981080PubMed 15496139PubMed 16503645. Source: MGI

heme binding

Inferred from direct assay PubMed 16503645. Source: MGI

iron ion binding

Inferred from direct assay PubMed 14981080. Source: MGI

iron-responsive element binding

Inferred from direct assay PubMed 7575558. Source: MGI

tetrapyrrole binding

Inferred from direct assay PubMed 14981080PubMed 15496139PubMed 16503645. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5353Mitochondrion Ref.1
Chain54 – 420367Ferrochelatase, mitochondrial HAMAP-Rule MF_00323
PRO_0000008874

Sites

Active site2271 By similarity
Active site3801 By similarity
Metal binding1931Iron-sulfur (2Fe-2S)
Metal binding4001Iron-sulfur (2Fe-2S) By similarity
Metal binding4031Iron-sulfur (2Fe-2S) By similarity
Metal binding4081Iron-sulfur (2Fe-2S) By similarity

Amino acid modifications

Modified residue561N6-acetyllysine Ref.6
Modified residue1351N6-succinyllysine Ref.5
Modified residue2871N6-acetyllysine; alternate Ref.6
Modified residue2871N6-succinyllysine; alternate Ref.5
Modified residue4121N6-acetyllysine; alternate Ref.6
Modified residue4121N6-succinyllysine; alternate Ref.5

Natural variations

Natural variant981M → K in Fechm1Pas. Ref.7

Experimental info

Sequence conflict1201E → EQY in AAA37615. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P22315 [UniParc].

Last modified November 1, 1991. Version 2.
Checksum: 9BC4DBD18727105A

FASTA42047,130
        10         20         30         40         50         60 
MLSASANMAA ALRAAGALLR EPLVHGSSRA CQPWRCQSGA AVAATTEKVH HAKTTKPQAQ 

        70         80         90        100        110        120 
PERRKPKTGI LMLNMGGPET LGEVQDFLQR LFLDRDLMTL PIQNKLAPFI AKRRTPKIQE 

       130        140        150        160        170        180 
RRIGGGSPIK MWTSKQGEGM VKLLDELSPA TAPHKYYIGF RYVHPLTEEA IEEMERDGLE 

       190        200        210        220        230        240 
RAIAFTQYPQ YSCSTTGSSL NAIYRYYNEV GQKPTMKWST IDRWPTHPLL IQCFADHILK 

       250        260        270        280        290        300 
ELNHFPEEKR SEVVILFSAH SLPMSVVNRG DPYPQEVGAT VHKVMEKLGY PNPYRLVWQS 

       310        320        330        340        350        360 
KVGPVPWLGP QTDEAIKGLC ERGRKNILLV PIAFTSDHIE TLYELDIEYS QVLAQKCGAE 

       370        380        390        400        410        420 
NIRRAESLNG NPLFSKALAD LVHSHIQSNK LCSTQLSLNC PLCVNPVCRK TKSFFTSQQL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, sequencing, and expression of mouse ferrochelatase."
Taketani S., Nakahashi Y., Osumi T., Tokunaga R.
J. Biol. Chem. 265:19377-19380(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 54-63.
[2]"Cloning of murine ferrochelatase."
Brenner D.A., Frasier F.
Proc. Natl. Acad. Sci. U.S.A. 88:849-853(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 26-420, PROTEIN SEQUENCE OF 239-243 AND 330-335.
Strain: ICR.
Tissue: Liver.
[3]"Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases."
Dailey H.A., Sellers V.M., Dailey T.A.
J. Biol. Chem. 269:390-395(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[4]"Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[5]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-287 AND LYS-412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast and Liver.
[6]"Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56; LYS-287 AND LYS-412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Ferrochelatase structural mutant (Fechm1Pas) in the house mouse."
Boulechfar S., Lamoril J., Montagutelli X., Guenet J.-L., Deybach J.-C., Nordmann Y., Dailey H., Grandchamp B., de Verneuil H.
Genomics 16:645-648(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FECHM1PAS LYS-98.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M61215 mRNA. Translation: AAA80530.1.
M59288 mRNA. Translation: AAA37615.1. Different initiation.
PIRA37972.
UniGeneMm.1070.

3D structure databases

ProteinModelPortalP22315.
SMRP22315. Positions 64-420.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP22315. 3 interactions.
MINTMINT-1842883.

PTM databases

PhosphoSiteP22315.

Proteomic databases

MaxQBP22315.
PaxDbP22315.
PRIDEP22315.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:95513. Fech.

Phylogenomic databases

eggNOGCOG0276.
HOVERGENHBG051898.
InParanoidP22315.
PhylomeDBP22315.

Enzyme and pathway databases

BRENDA4.99.1.1. 3474.
UniPathwayUPA00252; UER00325.

Gene expression databases

ArrayExpressP22315.
BgeeP22315.
CleanExMM_FECH.
GenevestigatorP22315.

Family and domain databases

HAMAPMF_00323. Ferrochelatase.
InterProIPR001015. Ferrochelatase.
IPR019772. Ferrochelatase_AS.
[Graphical view]
PANTHERPTHR11108. PTHR11108. 1 hit.
PfamPF00762. Ferrochelatase. 1 hit.
[Graphical view]
TIGRFAMsTIGR00109. hemH. 1 hit.
PROSITEPS00534. FERROCHELATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFECH. mouse.
PROP22315.
SOURCESearch...

Entry information

Entry nameHEMH_MOUSE
AccessionPrimary (citable) accession number: P22315
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: November 1, 1991
Last modified: June 11, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot