HEMH_DROME
ID HEMH_DROME Reviewed; 384 AA.
AC Q9V9S8; O76533; Q8IGA4; Q8IH67; Q8IMF9; Q95U82;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Ferrochelatase, mitochondrial;
DE EC=4.99.1.1;
DE AltName: Full=Heme synthase;
DE AltName: Full=Protoheme ferro-lyase;
DE Flags: Precursor;
GN Name=FeCh; ORFNames=CG2098;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND FUNCTION.
RX PubMed=9712849; DOI=10.1074/jbc.273.35.22311;
RA Sellers V.M., Wang K.-F., Johnson M.K., Dailey H.A.;
RT "Evidence that the fourth ligand to the 2Fe-2S cluster in animal
RT ferrochelatase is a cysteine. Characterization of the enzyme from
RT Drosophila melanogaster.";
RL J. Biol. Chem. 273:22311-22316(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A; B AND C).
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
CC -!- FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX
CC (PubMed:9712849). Terminal enzyme in heme biosynthesis
CC (PubMed:9712849). Contains four conserved cysteines that function as
CC cluster ligands and play a crucial role in maintaining protein
CC structure (PubMed:9712849). {ECO:0000269|PubMed:9712849,
CC ECO:0000303|PubMed:9712849}.
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 -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Note=Binds 1 [2Fe-2S] cluster.;
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
CC -!- SUBUNIT: Monomer. {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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=Q9V9S8-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9V9S8-2; Sequence=VSP_007689, VSP_007690;
CC Name=C;
CC IsoId=Q9V9S8-3; Sequence=VSP_007691, VSP_007692;
CC -!- SIMILARITY: Belongs to the ferrochelatase family. {ECO:0000305}.
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DR EMBL; AF076220; AAC26225.1; -; mRNA.
DR EMBL; AE014297; AAF57206.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14294.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14295.2; -; Genomic_DNA.
DR EMBL; AY058251; AAL13480.1; -; mRNA.
DR EMBL; BT001392; AAN71147.1; -; mRNA.
DR EMBL; BT001878; AAN71652.1; -; mRNA.
DR RefSeq; NP_524613.1; NM_079874.3. [Q9V9S8-1]
DR RefSeq; NP_733458.1; NM_170579.3. [Q9V9S8-3]
DR RefSeq; NP_733459.2; NM_170580.3. [Q9V9S8-2]
DR AlphaFoldDB; Q9V9S8; -.
DR SMR; Q9V9S8; -.
DR BioGRID; 68598; 2.
DR DIP; DIP-22800N; -.
DR STRING; 7227.FBpp0085208; -.
DR PaxDb; Q9V9S8; -.
DR PRIDE; Q9V9S8; -.
DR DNASU; 43757; -.
DR EnsemblMetazoa; FBtr0085849; FBpp0085208; FBgn0266268. [Q9V9S8-1]
DR EnsemblMetazoa; FBtr0085850; FBpp0085209; FBgn0266268. [Q9V9S8-3]
DR EnsemblMetazoa; FBtr0085851; FBpp0085210; FBgn0266268. [Q9V9S8-2]
DR GeneID; 43757; -.
DR KEGG; dme:Dmel_CG2098; -.
DR UCSC; CG2098-RA; d. melanogaster. [Q9V9S8-1]
DR CTD; 2235; -.
DR FlyBase; FBgn0266268; FeCH.
DR VEuPathDB; VectorBase:FBgn0266268; -.
DR eggNOG; KOG1321; Eukaryota.
DR GeneTree; ENSGT00390000016258; -.
DR InParanoid; Q9V9S8; -.
DR OMA; LGDPYHC; -.
DR PhylomeDB; Q9V9S8; -.
DR Reactome; R-DME-189451; Heme biosynthesis.
DR UniPathway; UPA00252; UER00325.
DR BioGRID-ORCS; 43757; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43757; -.
DR PRO; PR:Q9V9S8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0266268; Expressed in antenna and 33 other tissues.
DR Genevisible; Q9V9S8; DM.
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; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW 2Fe-2S; Alternative splicing; Heme biosynthesis; Iron; Iron-sulfur; Lyase;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Porphyrin biosynthesis; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..384
FT /note="Ferrochelatase, mitochondrial"
FT /id="PRO_0000008877"
FT ACT_SITE 190
FT /evidence="ECO:0000250"
FT ACT_SITE 343
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 363
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 366
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 371
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT VAR_SEQ 1..158
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_007689"
FT VAR_SEQ 159..173
FT /note="SGSSFNSIFTHYRSN -> MHNCSYLFDPLYLFS (in isoform B)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_007690"
FT VAR_SEQ 281
FT /note="G -> V (in isoform C)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_007691"
FT VAR_SEQ 282..384
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_007692"
FT CONFLICT 269
FT /note="P -> A (in Ref. 1; AAC26225)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 384 AA; 43597 MW; 923B3BE7606566C5 CRC64;
MFLHNTKFCR LASGLAGGVR NLSGQKPKTA ILMLNMGGPT HTDQVHDYLL RIMTDRDMIQ
LPVQSRLGPW IAQRRTPEVQ KKYKEIGGGS PILKWTELQG QLMCEQLDRI SPETAPHKHY
VGFRYVNPLT ENTLAEIEKD KPERVVLFSQ YPQYSCATSG SSFNSIFTHY RSNNLPSDIK
WSIIDRWGTH PLLIKTFAQR IRDELAKFVE TKRNDVVILF TAHSLPLKAV NRGDAYPSEI
GASVHMVMQE LGQTNPYSLA WQSKVGPLPW LAPATDDAIK GYVKQGLKNF ILVPIAFVNE
HIETLHELDI EYCDELAKEV GVEEIRRAAT PNDHPLFIDA LTNVVADHLK SQQAVNPKFL
MRCPMCSNPK CRESKSWYRQ LCSN
