FXN
entrez
2395
canonical
uniprot
Q16595
canonical
ensembl
ENSG00000165060
resolver
ensembl
ENSG00000285130
resolver
ensp
ENSP00000379652
resolver
ensp
ENSP00000419243
resolver
genesymbol
FXN
resolver
genesymbol_syn
FRDA
resolver
genesymbol_syn
X25
resolver
hgnc
HGNC:3951
resolver
uniprot
A0A0S2Z3G4
resolver
uniprot
A8MXJ6
resolver
uniprot
C9JJ89
resolver
uniprot
O15545
resolver
uniprot
O95656
resolver
uniprot
Q15294
resolver
uniprot
Q5VZ01
resolver
uniprot_entry
A0A0S2Z3G4_HUMAN
resolver
uniprot_entry
FRDA_HUMAN
resolver
uniprot_sec
A8MXJ6
resolver
uniprot_sec
C9JJ89
resolver
uniprot_sec
O15545
resolver
uniprot_sec
O95656
resolver
uniprot_sec
Q15294
resolver
uniprot_sec
Q5VZ01
resolver
amino_acid_sequence
MWTLGRRAVAGLLASPSPAQAQTLTRVPRPAELAPLCGRRGLRTDIDATCTPRRASSNQRGLNQIWNVKKQSVYLMNLRKSGTLGHPGSLDETTYERLAEETLDSLAEFFEDLADKPYTFEDYDVSFGSGVLTVKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA
uniprot
proteins
disease_involvement
DISEASE: Friedreich ataxia (FRDA) [MIM:229300]: Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region. {ECO:0000269|PubMed:10732799, ECO:0000269|PubMed:10874325, ECO:0000269|PubMed:19629184, ECO:0000269|PubMed:21298097, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:31101807, ECO:0000269|PubMed:9150176, ECO:0000269|PubMed:9779809, ECO:0000269|PubMed:9989622, ECO:0000269|Ref.40, ECO:0000269|Ref.7, ECO:0000269|Ref.8}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.16.3.1
uniprot
proteins
function
FUNCTION: [Frataxin mature form]: 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). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:11823441, ECO:0000269|PubMed:12755598, ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15123683, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1 (PubMed:20053667). May be involved in the cytoplasmic iron-sulfur protein biogenesis (PubMed:16091420). May contribute to oxidative stress resistance and overall cell survival (PubMed:16608849). {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}.
uniprot
proteins
mass_dalton
23135
uniprot
proteins
mutagenesis
MUTAGEN 39..40; /note="RR->GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210)."; /evidence="ECO:0000269|PubMed:18725397"; MUTAGEN 53..54; /note="RR->GG: No effect on processing of wild-type FXN."; /evidence="ECO:0000269|PubMed:17468497, ECO:0000269|PubMed:18725397"; MUTAGEN 78..79; /note="LR->GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210)."; /evidence="ECO:0000269|PubMed:18725397"; MUTAGEN 79..80; /note="RK->GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210)."; /evidence="ECO:0000269|PubMed:17468497, ECO:0000269|PubMed:18725397"; MUTAGEN 96; /note="E->K: Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 104; /note="D->G: Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 108; /note="E->K: Significantly reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 111; /note="E->K: Significantly reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 115; /note="D->K: Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 124; /note="D->K: Drastically reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 146; /note="N->A: Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097"; MUTAGEN 173; /note="W->G: Loss of interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing."; /evidence="ECO:0000269|PubMed:21298097
uniprot
proteins
post_translational_modification
PTM: Processed in two steps by mitochondrial processing peptidase (MPP). MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to yield frataxin mature form (frataxin(81-210)) which is the predominant form (PubMed:21298097). The additional forms, frataxin(56-210) and frataxin(78-210), seem to be produced when the normal maturation process is impaired; their physiological relevance is unsure. {ECO:0000269|PubMed:10428860, ECO:0000269|PubMed:10545606, ECO:0000269|PubMed:11020385, ECO:0000269|PubMed:17468497, ECO:0000269|PubMed:18725397, ECO:0000269|PubMed:21298097}.
uniprot
proteins
protein_family
Frataxin family
uniprot
proteins
pubmed
10428860
uniprot
proteins
pubmed
10545606
uniprot
proteins
pubmed
10732799
uniprot
proteins
pubmed
10874325
uniprot
proteins
pubmed
10900192
uniprot
proteins
pubmed
10903947
uniprot
proteins
pubmed
11020385
uniprot
proteins
pubmed
11823441
uniprot
proteins
pubmed
12755598
uniprot
proteins
pubmed
12785837
uniprot
proteins
pubmed
15123683
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15247478
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15581888
uniprot
proteins
pubmed
15641778
uniprot
proteins
pubmed
15961414
uniprot
proteins
pubmed
16091420
uniprot
proteins
pubmed
16239244
uniprot
proteins
pubmed
16608849
uniprot
proteins
pubmed
17331979
uniprot
proteins
pubmed
17468497
uniprot
proteins
pubmed
18725397
uniprot
proteins
pubmed
19629184
uniprot
proteins
pubmed
20053667
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21298097
uniprot
proteins
pubmed
24971490
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26702583
uniprot
proteins
pubmed
29576242
uniprot
proteins
pubmed
31101807
uniprot
proteins
pubmed
8596916
uniprot
proteins
pubmed
9150176
uniprot
proteins
pubmed
9241270
uniprot
proteins
pubmed
9302253
uniprot
proteins
pubmed
9779809
uniprot
proteins
pubmed
9989622
uniprot
proteins
sequence_length
210
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Frataxin mature form]: Mitochondrion {ECO:0000269|PubMed:15581888, ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:18725397, ECO:0000269|PubMed:20053667, ECO:0000269|PubMed:21298097, ECO:0000269|PubMed:9241270, ECO:0000269|PubMed:9302253}.; SUBCELLULAR LOCATION: [Extramitochondrial frataxin]: Cytoplasm, cytosol {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}.
uniprot
proteins