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Overview

Uniprot IDO35943
Protein NameFrataxin, mitochondrial
Gene NameFxn
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
189 LLARELTKALNTKLD

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:19805308, PubMed:25597503). 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:25597503). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (By similarity). 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. 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. May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation. 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 (By similarity)

Protein Sequence

10 MWAFGGRAAV 20 GLLPRTASRA 30 SAWVGNPRWR 40 EPIVTCGRRG 50 LHVTVNAGAT 60 RHAHLNLHYL 70 QILNIKKQSV 80 CVVHLRNLGT 90 LDNPSSLDET 100 AYERLAEETL 110 DSLAEFFEDL 120 ADKPYTLEDY 130 DVSFGDGVLT 140 IKLGGDLGTY 150 VINKQTPNKQ 160 IWLSSPSSGP 170 KRYDWTGKNW 180 VYSHDGVSLH 190 ELLARELTKA 200 LNTKLDLSSL AYSGKGT

Gene Ontology

Classification GO ID Description
Biological Process GO:0045773 positive regulation of axon extension
Biological Process GO:0051349 positive regulation of lyase activity
Biological Process GO:0035794 positive regulation of mitochondrial membrane permeability
Biological Process GO:0019230 proprioception
Biological Process GO:0016540 protein autoprocessing
Biological Process GO:0051604 protein maturation
Biological Process GO:0051480 regulation of cytosolic calcium ion concentration
Biological Process GO:0010039 response to iron ion
Cellular Component GO:0005829 cytosol
Cellular Component GO:0099128 mitochondrial [2Fe-2S] assembly complex
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:0019899 enzyme binding
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:0007628 adult walking behavior
Biological Process GO:0009060 aerobic respiration
Biological Process GO:0070301 cellular response to hydrogen peroxide
Biological Process GO:0009792 embryo development ending in birth or egg hatching
Biological Process GO:0006783 heme biosynthetic process
Biological Process GO:0006879 intracellular iron ion homeostasis
Biological Process GO:0048250 iron import into the mitochondrion
Biological Process GO:0016226 iron-sulfur cluster assembly
Biological Process GO:0007005 mitochondrion organization
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:0010888 negative regulation of lipid storage
Biological Process GO:0040015 negative regulation of multicellular organism growth
Biological Process GO:0043524 negative regulation of neuron apoptotic process
Biological Process GO:0046621 negative regulation of organ growth
Biological Process GO:0090201 negative regulation of release of cytochrome c from mitochondria
Biological Process GO:0006119 oxidative phosphorylation

Reference

[1] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.

[2] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.