P22315 (HEMH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ferrochelatase, mitochondrial
EC=4.99.1.1

Alternative name(s):
Heme synthase
Protoheme ferro-lyase

Gene names

Name:

Fech

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	420 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the ferrous insertion into protoporphyrin IX.
Catalytic activity	Protoheme + 2 H+ = protoporphyrin + Fe2+.
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.
Pathway	Porphyrin metabolism; protoheme biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
Subunit structure	Monomer By similarity.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Tissue specificity	Erythroid and hepatic cells.
Induction	During erythroid differentiation.
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 process	Heme biosynthesis Porphyrin biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Disease mutation
Domain	Transit peptide
Ligand	2Fe-2S Iron Iron-sulfur Metal-binding
Molecular function	Lyase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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 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 hemoglobin biosynthetic process Inferred from genetic interaction PubMed 15931390. Source: MGI very-low-density lipoprotein particle assembly Inferred from mutant phenotype PubMed 11160364. Source: MGI
Cellular_component	mitochondrial inner membrane Traceable author statement PubMed 12149233. Source: MGI
Molecular_function	2 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 53	53	Mitochondrion Ref.1
	Chain	54 – 420	367	Ferrochelatase, mitochondrial		PRO_0000008874
Sites
	Active site	227	1	By similarity
	Active site	380	1	By similarity
	Metal binding	193	1	Iron-sulfur (2Fe-2S)
	Metal binding	400	1	Iron-sulfur (2Fe-2S) By similarity
	Metal binding	403	1	Iron-sulfur (2Fe-2S) By similarity
	Metal binding	408	1	Iron-sulfur (2Fe-2S) By similarity
Natural variations
	Natural variant	98	1	M → K in Fechm1Pas. Ref.4
Experimental info
	Sequence conflict	120	1	E → EQY in AAA37615. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P22315 [UniParc]. Last modified November 1, 1991. Version 2. Checksum: 9BC4DBD18727105A	FASTA	420	47,130
	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

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]	"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.
IPI	IPI00228343.
PIR	A37972.
UniGene	Mm.1070.
3D structure databases
ProteinModelPortal	P22315.
SMR	P22315. Positions 64-420.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1842883.
PTM databases
PhosphoSite	P22315.
Proteomic databases
PaxDb	P22315.
PRIDE	P22315.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:95513. Fech.
Phylogenomic databases
eggNOG	COG0276.
HOVERGEN	HBG051898.
InParanoid	P22315.
Enzyme and pathway databases
BRENDA	4.99.1.1. 3474.
UniPathway	UPA00252; UER00325.
Gene expression databases
ArrayExpress	P22315.
Bgee	P22315.
CleanEx	MM_FECH.
Genevestigator	P22315.
GermOnline	ENSMUSG00000024588. Mus musculus.
Family and domain databases
InterPro	IPR001015. Ferrochelatase. IPR019772. Ferrochelatase_AS. [Graphical view]
PANTHER	PTHR11108. PTHR11108. 1 hit.
Pfam	PF00762. Ferrochelatase. 1 hit. [Graphical view]
TIGRFAMs	TIGR00109. hemH. 1 hit.
PROSITE	PS00534. FERROCHELATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FECH. mouse.
SOURCE	Search...

Entry information

Entry name

HEMH_MOUSE

Accession

Primary (citable) accession number: P22315

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	November 1, 1991
Last modified:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program