P22830 · HEMH_HUMAN
- ProteinFerrochelatase, mitochondrial
- GeneFECH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids423 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the ferrous insertion into protoporphyrin IX.
Catalytic activity
- 2 H+ + heme b = Fe2+ + protoporphyrin IX
Cofactor
Note: Binds 1 [2Fe-2S] cluster.
Activity regulation
Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor.
Pathway
Porphyrin-containing compound metabolism; protoheme biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 196 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Active site | 230 | |||||
Sequence: H | ||||||
Active site | 383 | |||||
Sequence: D | ||||||
Binding site | 403 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 406 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 411 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFerrochelatase, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP22830
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Protoporphyria, erythropoietic, 1 (EPP1)
- Note
- DescriptionAn autosomal recessive form of porphyria with onset usually before age 10 years. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.
- See alsoMIM:177000
Natural variants in EPP1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_002383 | 55 | G>C | in EPP1; dbSNP:rs3848519 | |
VAR_030553 | 62 | P>R | in EPP1; dbSNP:rs150830931 | |
VAR_030554 | 71 | I>K | in EPP1; enzyme totally inactive | |
VAR_030555 | 139 | Q>L | in EPP1; enzyme retains 18% of activity; dbSNP:rs1356965294 | |
VAR_030556 | 151 | S>P | in EPP1; enzyme totally inactive | |
VAR_030557 | 178 | E>K | in EPP1; dbSNP:rs1160565035 | |
VAR_030558 | 182 | L>R | in EPP1; enzyme totally inactive | |
VAR_002384 | 186 | I>T | in EPP1; dbSNP:rs1598996367 | |
VAR_030559 | 191 | Y>H | in EPP1; enzyme retains 72% of activity; dbSNP:rs1055019947 | |
VAR_030560 | 192 | P>T | in EPP1; enzyme totally inactive | |
VAR_030561 | 236 | C>Y | in EPP1; enzyme retains 12% of activity; dbSNP:rs761962617 | |
VAR_030562 | 260 | F>L | in EPP1; enzyme retains 52% of activity | |
VAR_054629 | 264 | S>L | in EPP1 | |
VAR_002385 | 267 | M>I | in EPP1; unchanged activity; but increased thermolability; dbSNP:rs118204037 | |
VAR_030563 | 283 | T>I | in EPP1; enzyme almost inactive | |
VAR_030564 | 288 | M>K | in EPP1; enzyme totally inactive | |
VAR_030565 | 334 | P>L | in EPP1; enzyme retains 19% of activity; dbSNP:rs150146721 | |
VAR_030566 | 362 | V>G | in EPP1; dbSNP:rs118204040 | |
VAR_030567 | 379 | K>N | in EPP1; enzyme retains 37% of activity | |
VAR_002386 | 386 | H>P | in EPP1; loss of activity | |
VAR_030568 | 406 | C>S | in EPP1; enzyme almost inactive | |
VAR_030569 | 406 | C>Y | in EPP1; enzyme almost inactive; dbSNP:rs1324421474 | |
VAR_030570 | 408-411 | NPVC>KSVG | in EPP1; no detectable enzymatic activity | |
VAR_002387 | 417 | F>S | in EPP1; reduced activity; dbSNP:rs118204039 | |
VAR_030571 | 417 | missing | in EPP1; enzyme totally inactive |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_002383 | 55 | in EPP1; dbSNP:rs3848519 | |||
Sequence: G → C | ||||||
Natural variant | VAR_030553 | 62 | in EPP1; dbSNP:rs150830931 | |||
Sequence: P → R | ||||||
Natural variant | VAR_030554 | 71 | in EPP1; enzyme totally inactive | |||
Sequence: I → K | ||||||
Natural variant | VAR_012028 | 96 | in dbSNP:rs1041951 | |||
Sequence: R → Q | ||||||
Mutagenesis | 110 | Increases activity inhibition upon interaction with PGRMC1. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_030555 | 139 | in EPP1; enzyme retains 18% of activity; dbSNP:rs1356965294 | |||
Sequence: Q → L | ||||||
Natural variant | VAR_030556 | 151 | in EPP1; enzyme totally inactive | |||
Sequence: S → P | ||||||
Natural variant | VAR_030557 | 178 | in EPP1; dbSNP:rs1160565035 | |||
Sequence: E → K | ||||||
Natural variant | VAR_030558 | 182 | in EPP1; enzyme totally inactive | |||
Sequence: L → R | ||||||
Natural variant | VAR_002384 | 186 | in EPP1; dbSNP:rs1598996367 | |||
Sequence: I → T | ||||||
Natural variant | VAR_030559 | 191 | in EPP1; enzyme retains 72% of activity; dbSNP:rs1055019947 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_030560 | 192 | in EPP1; enzyme totally inactive | |||
Sequence: P → T | ||||||
Mutagenesis | 196 | Loss of activity. | ||||
Sequence: C → S | ||||||
Natural variant | VAR_030561 | 236 | in EPP1; enzyme retains 12% of activity; dbSNP:rs761962617 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_030562 | 260 | in EPP1; enzyme retains 52% of activity | |||
Sequence: F → L | ||||||
Natural variant | VAR_054629 | 264 | in EPP1 | |||
Sequence: S → L | ||||||
Natural variant | VAR_002385 | 267 | in EPP1; unchanged activity; but increased thermolability; dbSNP:rs118204037 | |||
Sequence: M → I | ||||||
Natural variant | VAR_030563 | 283 | in EPP1; enzyme almost inactive | |||
Sequence: T → I | ||||||
Natural variant | VAR_030564 | 288 | in EPP1; enzyme totally inactive | |||
Sequence: M → K | ||||||
Natural variant | VAR_030565 | 334 | in EPP1; enzyme retains 19% of activity; dbSNP:rs150146721 | |||
Sequence: P → L | ||||||
Mutagenesis | 360 | No loss of activity. | ||||
Sequence: C → S | ||||||
Natural variant | VAR_030566 | 362 | in EPP1; dbSNP:rs118204040 | |||
Sequence: V → G | ||||||
Natural variant | VAR_030567 | 379 | in EPP1; enzyme retains 37% of activity | |||
Sequence: K → N | ||||||
Natural variant | VAR_002386 | 386 | in EPP1; loss of activity | |||
Sequence: H → P | ||||||
Mutagenesis | 395 | No loss of activity. | ||||
Sequence: C → S | ||||||
Mutagenesis | 403 | Loss of activity. | ||||
Sequence: C → D or H | ||||||
Natural variant | VAR_030568 | 406 | in EPP1; enzyme almost inactive | |||
Sequence: C → S | ||||||
Natural variant | VAR_030569 | 406 | in EPP1; enzyme almost inactive; dbSNP:rs1324421474 | |||
Sequence: C → Y | ||||||
Mutagenesis | 406 | Loss of activity. | ||||
Sequence: C → D, H, or S | ||||||
Natural variant | VAR_030570 | 408-411 | in EPP1; no detectable enzymatic activity | |||
Sequence: NPVC → KSVG | ||||||
Mutagenesis | 411 | Loss of activity. | ||||
Sequence: C → H or S | ||||||
Natural variant | VAR_002387 | 417 | in EPP1; reduced activity; dbSNP:rs118204039 | |||
Sequence: F → S | ||||||
Natural variant | VAR_030571 | 417 | in EPP1; enzyme totally inactive | |||
Sequence: Missing | ||||||
Mutagenesis | 417 | Decreased activity. | ||||
Sequence: F → L | ||||||
Mutagenesis | 417 | Greatly reduced activity. | ||||
Sequence: F → Y or W |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 475 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-54 | Mitochondrion | ||||
Sequence: MRSLGANMAAALRAAGVLLRDPLASSSWRVCQPWRWKSGAAAAAVTTETAQHAQ | ||||||
Chain | PRO_0000008873 | 55-423 | Ferrochelatase, mitochondrial | |||
Sequence: GAKPQVQPQKRKPKTGILMLNMGGPETLGDVHDFLLRLFLDRDLMTLPIQNKLAPFIAKRRTPKIQEQYRRIGGGSPIKIWTSKQGEGMVKLLDELSPNTAPHKYYIGFRYVHPLTEEAIEEMERDGLERAIAFTQYPQYSCSTTGSSLNAIYRYYNQVGRKPTMKWSTIDRWPTHHLLIQCFADHILKELDHFPLEKRSEVVILFSAHSLPMSVVNRGDPYPQEVSATVQKVMERLEYCNPYRLVWQSKVGPMPWLGPQTDESIKGLCERGRKNILLVPIAFTSDHIETLYELDIEYSQVLAKECGVENIRRAESLNGNPLFSKALADLVHSHIQSNELCSKQLTLSCPLCVNPVCRETKSFFTSQQL | ||||||
Modified residue | 57 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 138 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 415 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 415 | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:17261801, PubMed:30765471).
Interacts with PGRMC1; the interaction results in decreased FECH activity (PubMed:27599036).
Interacts with ABCB10 and SLC25A37; this interaction forms an oligomeric complex (By similarity).
Forms a complex with ABCB7 and ABCB10, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471).
Interacts with ABCB7 and ABCB10 (PubMed:30765471).
Interacts with PGRMC1; the interaction results in decreased FECH activity (PubMed:27599036).
Interacts with ABCB10 and SLC25A37; this interaction forms an oligomeric complex (By similarity).
Forms a complex with ABCB7 and ABCB10, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471).
Interacts with ABCB7 and ABCB10 (PubMed:30765471).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P22830 | ABCB10 Q9NRK6 | 2 | EBI-1390356, EBI-6164528 | |
BINARY | P22830 | ABCB7 O75027 | 9 | EBI-1390356, EBI-1236950 | |
BINARY | P22830 | FECH P22830 | 4 | EBI-1390356, EBI-1390356 | |
BINARY | P22830 | PGRMC1 O00264 | 4 | EBI-1390356, EBI-1045534 | |
BINARY | P22830 | TIMP2 P16035 | 2 | EBI-1390356, EBI-1033507 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P22830-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length423
- Mass (Da)47,862
- Last updated2005-05-10 v2
- Checksum3FD50965E8DEABCE
P22830-2
- Name2
- Differences from canonical
- 64-64: K → KRYESNI
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A499FJN5 | A0A499FJN5_HUMAN | FECH | 351 | ||
K7EJX5 | K7EJX5_HUMAN | FECH | 143 | ||
K7EJM8 | K7EJM8_HUMAN | FECH | 111 | ||
K7ELX4 | K7ELX4_HUMAN | FECH | 326 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_041208 | 64 | in isoform 2 | |||
Sequence: K → KRYESNI | ||||||
Sequence conflict | 228 | in Ref. 4; BAC03882 | ||||
Sequence: P → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D00726 EMBL· GenBank· DDBJ | BAA00628.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ250235 EMBL· GenBank· DDBJ | CAB65962.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT019958 EMBL· GenBank· DDBJ | AAV38761.1 EMBL· GenBank· DDBJ | mRNA | ||
AK092416 EMBL· GenBank· DDBJ | BAC03882.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292937 EMBL· GenBank· DDBJ | BAF85626.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471096 EMBL· GenBank· DDBJ | EAW63046.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC039841 EMBL· GenBank· DDBJ | AAH39841.2 EMBL· GenBank· DDBJ | mRNA | ||
L36178 EMBL· GenBank· DDBJ | AAA64787.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF495859 EMBL· GenBank· DDBJ | AAM18070.1 EMBL· GenBank· DDBJ | Genomic DNA |