HEMH_BOVIN
ID HEMH_BOVIN Reviewed; 416 AA.
AC P22600;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Ferrochelatase, mitochondrial {ECO:0000250|UniProtKB:P22830};
DE EC=4.99.1.1 {ECO:0000250|UniProtKB:P22830};
DE AltName: Full=Heme synthase;
DE AltName: Full=Protoheme ferro-lyase;
DE Flags: Precursor;
GN Name=FECH {ECO:0000250|UniProtKB:P22830};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7640290; DOI=10.1016/0005-2728(95)00077-v;
RA Shibuya H., Nonneman D., Tamassia M., Allphin O.L., Johnson G.S.;
RT "The coding sequence of the bovine ferrochelatase gene.";
RL Biochim. Biophys. Acta 1231:117-120(1995).
RN [2]
RP PROTEIN SEQUENCE OF 281-311.
RC TISSUE=Liver;
RX PubMed=1704134; DOI=10.1073/pnas.88.3.849;
RA Brenner D.A., Frasier F.;
RT "Cloning of murine ferrochelatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:849-853(1991).
RN [3]
RP PROTEIN SEQUENCE OF 152-157; 266-275; 284-291 AND 373-381.
RX PubMed=2246229; DOI=10.1016/s0021-9258(17)45378-6;
RA Taketani S., Nakahashi Y., Osumi T., Tokunaga R.;
RT "Molecular cloning, sequencing, and expression of mouse ferrochelatase.";
RL J. Biol. Chem. 265:19377-19380(1990).
CC -!- FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
CC {ECO:0000250|UniProtKB:P22830}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + heme b = Fe(2+) + protoporphyrin IX;
CC Xref=Rhea:RHEA:22584, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:57306, ChEBI:CHEBI:60344; EC=4.99.1.1;
CC Evidence={ECO:0000250|UniProtKB:P22830};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0000250|UniProtKB:P22830};
CC -!- ACTIVITY REGULATION: Inhibited by nitric oxide (NO). The 2Fe-2S cluster
CC could act as a NO sensor (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
CC -!- SUBUNIT: Homodimer (By similarity). Interaction with PGRMC1; the
CC interaction results in decreased FECH activity (By similarity).
CC Interacts with ABCB10 and SLC25A37; this interaction forms an
CC oligomeric complex (By similarity). Forms a complex with ABCB7 and
CC ABCB10, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this
CC complex may be required for cellular iron homeostasis, mitochondrial
CC function and heme biosynthesis. Interacts with ABCB7 and ABCB10 (By
CC similarity). {ECO:0000250|UniProtKB:P22315,
CC ECO:0000250|UniProtKB:P22830}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P22315}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P22315}; Matrix side
CC {ECO:0000250|UniProtKB:P22315}.
CC -!- SIMILARITY: Belongs to the ferrochelatase family. {ECO:0000305}.
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DR EMBL; L34173; AAA79169.1; -; mRNA.
DR PIR; I45890; I45890.
DR RefSeq; NP_776479.1; NM_174054.2.
DR AlphaFoldDB; P22600; -.
DR SMR; P22600; -.
DR STRING; 9913.ENSBTAP00000008384; -.
DR iPTMnet; P22600; -.
DR PaxDb; P22600; -.
DR PRIDE; P22600; -.
DR Ensembl; ENSBTAT00000008384; ENSBTAP00000008384; ENSBTAG00000006393.
DR GeneID; 281158; -.
DR KEGG; bta:281158; -.
DR CTD; 2235; -.
DR VEuPathDB; HostDB:ENSBTAG00000006393; -.
DR VGNC; VGNC:28943; FECH.
DR eggNOG; KOG1321; Eukaryota.
DR GeneTree; ENSGT00390000016258; -.
DR HOGENOM; CLU_018884_1_0_1; -.
DR InParanoid; P22600; -.
DR OMA; LGDPYHC; -.
DR OrthoDB; 1003638at2759; -.
DR TreeFam; TF300859; -.
DR SABIO-RK; P22600; -.
DR UniPathway; UPA00252; UER00325.
DR Proteomes; UP000009136; Chromosome 24.
DR Bgee; ENSBTAG00000006393; Expressed in biceps femoris and 105 other tissues.
DR ExpressionAtlas; P22600; baseline and differential.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004325; F:ferrochelatase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0046501; P:protoporphyrinogen IX metabolic process; IEA:Ensembl.
DR CDD; cd00419; Ferrochelatase_C; 1.
DR CDD; cd03411; Ferrochelatase_N; 1.
DR HAMAP; MF_00323; Ferrochelatase; 1.
DR InterPro; IPR001015; Ferrochelatase.
DR InterPro; IPR019772; Ferrochelatase_AS.
DR InterPro; IPR033644; Ferrochelatase_C.
DR InterPro; IPR033659; Ferrochelatase_N.
DR PANTHER; PTHR11108; PTHR11108; 1.
DR Pfam; PF00762; Ferrochelatase; 1.
DR TIGRFAMs; TIGR00109; hemH; 1.
DR PROSITE; PS00534; FERROCHELATASE; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Acetylation; Direct protein sequencing; Heme biosynthesis; Iron;
KW Iron-sulfur; Lyase; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Porphyrin biosynthesis; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..47
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 48..416
FT /note="Ferrochelatase, mitochondrial"
FT /id="PRO_0000008872"
FT REGION 41..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 223
FT /evidence="ECO:0000250"
FT ACT_SITE 376
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 396
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 399
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 404
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT MOD_RES 131
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT MOD_RES 283
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT MOD_RES 283
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT MOD_RES 408
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT MOD_RES 408
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P22315"
FT CONFLICT 282
FT /note="D -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="S -> P (in Ref. 2; AA sequence and 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 46935 MW; ECE1D43F9DC4B78E CRC64;
MAAALRSAGV LLRDRLLYGG SRACQPRRCQ SGAATAAAAT ETAQRARSPK PQAQPGNRKP
RTGILMLNMG GPETVEEVQD FLQRLFLDQD LMTLPVQDKL GPFIAKRRTP KIQEQYRRIG
GGSPIKMWTS KQGEGMVKLL DELSPHTAPH KYYIGFRYVH PLTEEAIEEM ERDGLERAVA
FTQYPQYSCS TTGSSLNAIY RYYNEVGRKP TMKWSTIDRW PTHPLLIQCF ADHILKELDH
FPPEKRREVV ILFSAHSLPM SVVNRGDPYP QEVGATVQRV MDKLGYSNPY RLVWQSKVGP
MPWLGPQTDE AIKGLCKRGR KNILLVPIAF TSDHIETLYE LDIEYSQVLA SECGLENIRR
AESLNGNPLF SKALADLVHS HLQSKERCST QLTLSCPLCV NPTCRETKSF FTSQQL
