Overview
| Uniprot ID | Q16595 |
|---|
| Protein Name | Frataxin, mitochondrial |
|---|
| Gene Name | FXN |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 197 |
LTKALKTKLDLSSLA |
Function
Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:12785837, PubMed:24971490). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (PubMed:15123683, PubMed:16239244)
Protein Sequence
10
MWTLGRRAVA
20
GLLASPSPAQ
30
AQTLTRVPRP
40
AELAPLCGRR
50
GLRTDIDATC
60
TPRRASSNQR
70
GLNQIWNVKK
80
QSVYLMNLRK
90
SGTLGHPGSL
100
DETTYERLAE
110
ETLDSLAEFF
120
EDLADKPYTF
130
EDYDVSFGSG
140
VLTVKLGGDL
150
GTYVINKQTP
160
NKQIWLSSPS
170
SGPKRYDWTG
180
KNWVYSHDGV
190
SLHELLAAEL
200
TKALKTKLDL
210
SSLAYSGKDA
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0099128 |
mitochondrial [2Fe-2S] assembly complex |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Molecular Function |
GO:0051537 |
2 iron, 2 sulfur cluster binding |
| Molecular Function |
GO:0008047 |
enzyme activator activity |
| Molecular Function |
GO:0008199 |
ferric iron binding |
| Molecular Function |
GO:0008198 |
ferrous iron binding |
| Molecular Function |
GO:0004322 |
ferroxidase activity |
| Molecular Function |
GO:0034986 |
iron chaperone activity |
| Biological Process |
GO:0044571 |
[2Fe-2S] cluster assembly |
| Biological Process |
GO:0044572 |
[4Fe-4S] cluster assembly |
| Biological Process |
GO:0070301 |
cellular response to hydrogen peroxide |
| Biological Process |
GO:0006783 |
heme biosynthetic process |
| Biological Process |
GO:0006879 |
intracellular iron ion homeostasis |
| Biological Process |
GO:0006826 |
iron ion transport |
| Biological Process |
GO:0016226 |
iron-sulfur cluster assembly |
| Biological Process |
GO:0034551 |
mitochondrial respiratory chain complex III assembly |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0090201 |
negative regulation of release of cytochrome c from mitochondria |
| Biological Process |
GO:0051349 |
positive regulation of lyase activity |
| Biological Process |
GO:0016540 |
protein autoprocessing |
| Biological Process |
GO:0051604 |
protein maturation |
| Biological Process |
GO:0010039 |
response to iron ion |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.