hem15

UniProt ID: O59786
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

hem15 (SPCC320.09; UniProt O59786) encodes ferrochelatase (protoporphyrin ferrochelatase; EC 4.98.1.1), the terminal enzyme of heme biosynthesis. It sits on the inner mitochondrial membrane with its active site facing the matrix and inserts ferrous iron into protoporphyrin IX to form protoheme (heme b). Unlike S. cerevisiae Hem15, but like animal ferrochelatases, the S. pombe enzyme has four C-terminal cysteines that ligate a [2Fe-2S] cluster, which has been detected spectroscopically.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004325 protoporphyrin ferrochelatase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA from ferrochelatase node PTN000121751 (PTHR11108), with experimental seeds including S. cerevisiae HEM15, human FECH, mouse Fech and Arabidopsis FC1/FC2; hem15 is in the ferrochelatase family (HAMAP MF_00323, TIGR00109); sound.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
PANTHER; PTHR11108; FERROCHELATASE; 1.
file:SCHPO/hem15/hem15-uniprot.txt
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
file:SCHPO/hem15/hem15-uniprot.txt
Reaction=heme b + 2 H(+) = protoporphyrin IX + Fe(2+);
GO:0004325 protoporphyrin ferrochelatase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: EC/RHEA mapping; consistent.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
Reaction=heme b + 2 H(+) = protoporphyrin IX + Fe(2+);
GO:0005634 nucleus
IEA
GO_REF:0000044 		MARK AS OVER ANNOTATED
Summary: UniProt location mapping of the ORFeome screen nuclear signal. No nuclear role is known.
Reason: Ferrochelatase is a mitochondrial inner-membrane enzyme with its active site on the matrix side; extramitochondrial YFP signal from a C-terminally tagged, overexpressed high-throughput screen most likely reflects the precursor or a tag artefact. Not removed, because a minor extramitochondrial pool is not excluded, but the location is over-annotated.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
PMID:7629135
is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		MARK AS OVER ANNOTATED
Summary: UniProt location mapping of the ORFeome screen cytoplasmic signal. Ferrochelatase acts in mitochondria; the signal may reflect the tagged precursor.
Reason: Ferrochelatase is a mitochondrial inner-membrane enzyme with its active site on the matrix side; extramitochondrial YFP signal from a C-terminally tagged, overexpressed high-throughput screen most likely reflects the precursor or a tag artefact. Not removed, because a minor extramitochondrial pool is not excluded, but the location is over-annotated.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
PMID:7629135
is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA is_active_in mitochondrion from PTN008512544 (eukaryotic ferrochelatases; IBD seeds S. cerevisiae HEM15, mouse Fech, human FECH, Arabidopsis FC1). Checked the seeds: all are organellar enzymes, and the yeast ortholog acts on the matrix side of the inner membrane. The organelle claim holds; the sub-compartment is captured by the GO:0005743 and GO:0099617 rows.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
PANTHER; PTHR11108; FERROCHELATASE; 1.
file:SCHPO/hem15/hem15-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}.
PMID:7629135
is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Inner-membrane location by similarity; consistent with the S. cerevisiae HEM15 review.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}.
PMID:7629135
is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane
GO:0006783 heme biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Terminal step of heme biosynthesis.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
PANTHER; PTHR11108; FERROCHELATASE; 1.
file:SCHPO/hem15/hem15-uniprot.txt
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
GO:0006783 heme biosynthetic process
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro mapping; consistent.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
GO:0051537 2 iron, 2 sulfur cluster binding
IDA
PMID:11948160
Identification of [2Fe-2S] clusters in microbial ferrochelat... 		ACCEPT
Summary: S. pombe ferrochelatase contains a [2Fe-2S] cluster, ligated by cysteines in the same positions as in animal ferrochelatases; S. cerevisiae HEM15 has none. A notable S. pombe-specific feature.
Supporting Evidence:
PMID:11948160
Previously, as part of a study on the carboxyl termini of eukaryotic ferrochelatases, it was determined that S. pombe ferrochelatase contains a [2Fe-2S] cluster
PMID:11948160
The amino acid sequence of S. pombe ferrochelatase contains cysteines analogous to the [2Fe-2S] four cluster-ligating cysteines that are found in animal ferrochelatases.
GO:0099617 matrix side of mitochondrial inner membrane
IC
GO_REF:0000111 		ACCEPT
Summary: Curator inference: the ferrochelatase active site faces the matrix, where it receives protoporphyrin IX and ferrous iron. Shown for the S. cerevisiae ortholog by fractionation (PMID:7629135) and recorded by UniProt for eukaryotic ferrochelatases; a TM-free peripheral protein that inserts iron into a matrix-side substrate. Accepted.
Supporting Evidence:
file:SCHPO/hem15/hem15-uniprot.txt
Note=Bound to the mitochondrial inner membrane in eukaryotic cells with its active site on the matrix side of the membrane.
PMID:7629135
is synthesized in the cytoplasm in a precursor form and then is translocated to the matrix side of the inner mitochondrial membrane

Core Functions

Matrix-facing inner-membrane ferrochelatase containing a [2Fe-2S] cluster: protoporphyrin IX + Fe2+ -> heme b.

Molecular Function:
protoporphyrin ferrochelatase activity
Directly Involved In:
heme biosynthetic process
Cellular Locations:
matrix side of mitochondrial inner membrane
Supporting Evidence:
  • file:SCHPO/hem15/hem15-uniprot.txt
    FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
  • file:SCHPO/hem15/hem15-uniprot.txt
    Reaction=heme b + 2 H(+) = protoporphyrin IX + Fe(2+);
  • file:SCHPO/hem15/hem15-uniprot.txt
    Note=Bound to the mitochondrial inner membrane in eukaryotic cells with its active site on the matrix side of the membrane.
  • PMID:11948160
    Previously, as part of a study on the carboxyl termini of eukaryotic ferrochelatases, it was determined that S. pombe ferrochelatase contains a [2Fe-2S] cluster

References

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📚 Additional Documentation

Notes

(hem15-notes.md)

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