TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
2.A.54.1.1









Mitochondrial serine (and possibly cystine and alanine) carrier, Sideroflexin-1 (SFXN1), of 322 aas and probably 5 TMSs (Kory et al. 2018). This system is believed to be required for one-carbon metabolism because serine is converted into glycine and formate in the mitochondrion. SFXN1, an integral inner mitochondrial membrane (IMM) protein with an uneven number of transmembrane domains, is a TIM22 complex substrate. An SFXN1 deficiency leads to mitochondrial respiratory chain impairments, the most detrimental being to complex III (CIII) biogenesis, activity, and assembly, compromising coenzyme Q levels (Acoba et al. 2021). The CIII dysfunction is independent of one-carbon metabolism, the known primary role for SFXN1 as a mitochondrial serine transporter. Instead, SFXN1 supports CIII function by participating in heme and alpha-ketoglutarate metabolism. Thus, SFXN1-based amino acid transport impacts mitochondrial and cellular metabolic efficiency in multiple ways. The TIM22 complex mediates the import of sideroflexins which transport L- and D-serine and other amino acids, and it is therefore required for efficient mitochondrial one-carbon metabolism (Jackson et al. 2021).

Eukaryota
Metazoa
SFXN1 of Homo sapiens
2.A.54.1.2









Hypothetical 36.7 KDa protein AH6.2
Eukaryota
Metazoa
AH6.2 of Caenorhabditis elegans
2.A.54.1.3









Sideroflexin-4 (Breast cancer resistance marker 1) of 337 aas and 5 or 6 TMSs in a 1 or 2 +2 + 2 TMS arrangement. It has been found mutated in mice with siderocytic anemia (Zheng et al. 2003).

Eukaryota
Metazoa
Sideroflexin-4 of Homo sapiens
2.A.54.1.4









Probable mitochondrial transport protein FSF1 (Fungal sideroflexin-1)
Eukaryota
Fungi
FSF1 of Saccharomyces cerevisiae
2.A.54.1.5









Sideroflexin-5 (SFXN5) of 342 aas and 5 TMSs in a 1 + 2 + 2 TMS arrangement. The identification and characterization of the human sideroflexin 5 gene, and its high expression in the brain have been reported (Lockhart et al. 2002). It does not appear to be a Parkinson disease protein.

Eukaryota
Metazoa
Sfxn5 of Mus musculus
2.A.54.1.6









Sideroflexin-3, Sfxn3, of 321 aas and 4 TMSs in a 2 + 2 TMS arrangement. It is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology (Amorim et al. 2017). It is highly expressed in mature neurons of the mouse, with expression developing as development occurs from birth to adulthood.  Within neurons, Sfxn3 localizes to mitochondria in all major neuronal compartments (Rivell et al. 2019).

Eukaryota
Metazoa
Sfxn3 of Mus musculus
2.A.54.1.7









Tricarboxylic acid (TCA) transporter of 327 aas and 6 TMSs. Found to be essential for bloodstream-form Trypanosoma brucei through a genome-wide RNAi screen (Schmidt et al. 2018).

Eukaryota
Kinetoplastida
TCA carrier of Trypanosoma brucei
2.A.54.1.8









Sideroflexin 2, SFXN2 of 322 aas and 5 or 6 TMSs in a 1 or 2 + 2 + 2 TMS arrangement.  SFXN2 is involved in mitochondrial iron metabolism and is localized to the mitochondrial inner membrane (Mon et al. 2019). SFXN2-knockout (KO) cells have an increased mitochondrial iron content and decreases in the heme content and heme-dependent enzyme activities. By contrast, the activities of iron-sulfur cluster-dependent enzymes were unchanged. Abnormal iron metabolism impaired mitochondrial respiration in SFXN2-KO cells and accelerated iron-mediated death (Mon et al. 2019). It may exert its effects by alterning heme biosynthesis.

Eukaryota
Metazoa
SFXN2 of Homo sapiens
2.A.54.1.9









Sideroflexin4, SFXN4, of 479 aas and possibly 7 TMSs in a 1 + 2 + 2 + 2 TMS arrangement, is important for mitochondrial function.  Macrocytic anemia and mitochondriopathy result from a defect in SFXN4in humans (Hildick-Smith et al. 2013).

 

Eukaryota
Metazoa
SFXN4 of Sturnus vulgaris
2.A.54.1.10









Sideroflexin-4 isoform X4 of 327 aas and 7 probable TMSs in a 1 + 2 + 2 + 2 TMS arrangement. Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes (Paul et al. 2019; Gyimesi and Hediger 2020).

Eukaryota
Metazoa
SFXN4 of Pogona vitticeps
2.A.54.1.11









Uncharacterized protein of 331 aas and 6 putative TMSs in a 2 + 2 + 2 TMS arrangement.

Eukaryota
Oomycetes
UP of Peronospora effusa
2.A.54.1.12









Putative tricarboxylate/iron carrier of 332 aas and 5 or 6 TMSs in a 1 or 2 + 2 + 2 TMS arrangment.

Eukaryota
Fungi
UP of Glomus cerebriforme
2.A.54.1.13









Sideroflexin 5 of 310 aas and 5 TMSs in a 1 + 2 + 2 TMS arrangement.

Eukaryota
Haptista
SFXN5 of Chrysochromulina tobinii