SLC25A46

Last updated
SLC25A46
Identifiers
Aliases SLC25A46 , HMSN6B, solute carrier family 25 member 46
External IDs OMIM: 610826 MGI: 1914703 HomoloGene: 14518 GeneCards: SLC25A46
Gene location (Human)
Ideogram human chromosome 5.svg
Chr. Chromosome 5 (human) [1]
Human chromosome 5 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 5q22.1Start110,738,136 bp [1]
End110,765,161 bp [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001303249
NM_001303250
NM_138773

NM_026165
NM_001357461

RefSeq (protein)

NP_001290178
NP_001290179
NP_620128

NP_080441
NP_001344390

Location (UCSC) Chr 5: 110.74 – 110.77 Mb Chr 18: 31.56 – 31.61 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Solute carrier family 25 member 46 is a protein that in humans is encoded by the SLC25A46 gene. This protein is a member of the SLC25 mitochondrial solute carrier family. It is a transmembrane protein located in the mitochondrial outer membrane involved in lipid transfer from the endoplasmic reticulum (ER) to mitochondria. [5] [6] Mutations in this gene result in neuropathy and optic atrophy. [7]

Contents

Structure

The SLC25A46 gene is located on the q arm of chromosome 5 in position 22.1 and spans 27,039 base pairs. [7] The gene produces a 46.2 kDa protein composed of 418 amino acids. [8] [9] This gene has 8 exons and encodes a multi-pass integral membrane protein localized to the mitochondrial outer membrane. [10] [11] [12]

Function

The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria. [13] [6] It promotes mitochondrial fission and prevents the formation of hyperfilamentous mitochondria. This protein forms a complex with mitofilin (IMMT) on the inner mitochondrial membrane, independent of MFN2. [5]

Clinical Significance

Mutations in the SLC25A46 gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. [11] [12]

Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission. [5] Loss of this gene also has many other effects: premature cellular senescence, impaired cellular respiration, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER morphology, impaired cell migration, and changes in mitochondrial phospholipid composition. [6]

Interactions

This protein interacts with IMMT, a component of the MICOS complex, along with other components of this complex and components of an ER membrane protein complex involved in transferring lipids to mitochondria. [11] [12] [6] Additionally, this protein interacts with SLC7A8, SLC10A1, SLC10A6, FHL3, FUNDC1, linc01142, LEPROTL1, ODF4, VMA21, MFSD14B, PQLC1, HSD17B11, REEP2, REEP4, and TOMM22. [14] This protein possibly interacts with OPA1 and MFN2. [6]

Related Research Articles

Mitochondrial carrier

Mitochondrial carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in the Transporter Classification Database. The Mitochondrial Carrier (MC) Superfamily has been expanded to include both the original Mitochondrial Carrier (MC) family and the Mitochondrial Inner/Outer Membrane Fusion (MMF) family.

MFN2

Mitofusin-2 is a protein that in humans is encoded by the MFN2 gene. Mitofusins are GTPases embedded in the outer membrane of the mitochondria. In mammals MFN1 and MFN2 are essential for mitochondrial fusion. In addition to the mitofusins, OPA1 regulates inner mitochondrial membrane fusion, and DRP1 is responsible for mitochondrial fission.

Dynamin-like 120 kDa protein

Dynamin-like 120 kDa protein, mitochondrial is a protein that in humans is encoded by the OPA1 gene. This protein regulates mitochondrial fusion and cristae structure in the inner mitochondrial membrane (IMM) and contributes to ATP synthesis and apoptosis, and small, round mitochondria. Mutations in this gene have been implicated in dominant optic atrophy (DOA), leading to loss in vision, hearing, muscle contraction, and related dysfunctions.

Phosphate carrier protein, mitochondrial

Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene. The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation. There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function. Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.

Mitochondrial 2-oxoglutarate/malate carrier protein

Mitochondrial 2-oxoglutarate/malate carrier protein is a protein that in humans is encoded by the SLC25A11 gene. Inactivating mutations in this gene predispose to metastasic paraganglioma.

Brain mitochondrial carrier protein 1

Brain mitochondrial carrier protein 1 is a protein that in humans is encoded by the SLC25A14 gene.

Mitochondrial thiamine pyrophosphate carrier

Mitochondrial thiamine pyrophosphate carrier is a protein that in humans is encoded by the SLC25A19 gene.

Mitochondrial dicarboxylate carrier

The mitochondrial dicarboxylate carrier (DIC) is an integral membrane protein encoded by the SLC25A10 gene in humans that catalyzes the transport of dicarboxylates such as malonate, malate, and succinate across the inner mitochondrial membrane in exchange for phosphate, sulfate, and thiosulfate by a simultaneous antiport mechanism, thus supplying substrates for the Krebs cycle, gluconeogenesis, urea synthesis, fatty acid synthesis, and sulfur metabolism.

Calcium-binding mitochondrial carrier protein Aralar1

Calcium-binding mitochondrial carrier protein Aralar1 is a protein that in humans is encoded by the SLC25A12 gene. Aralar is an integral membrane protein located in the inner mitochondrial membrane. Its primary function as an antiporter is the transport of cytoplasmic glutamate with mitochondrial aspartate across the inner mitochondrial membrane, dependent on the binding of one calcium ion. Mutations in this gene cause early infantile epileptic encephalopathy 39 (EIEE39), symptomized by global hypomyelination of the central nervous system, refractory seizures, and neurodevelopmental impairment. This gene has connections to autism.

Long-chain fatty acid transport protein 1

Long-chain fatty acid transport protein 1 (FATP1) is a protein that in humans is encoded by the SLC27A1 gene.

SLC25A39

Solute carrier family 25 member 39 is a protein that in humans is encoded by the SLC25A39 gene.

Tricarboxylate transport protein, mitochondrial

Tricarboxylate transport protein, mitochondrial, also known as tricarboxylate carrier protein and citrate transport protein (CTP), is a protein that in humans is encoded by the SLC25A1 gene. SLC25A1 belongs to the mitochondrial carrier gene family SLC25. High levels of the tricarboxylate transport protein are found in the liver, pancreas and kidney. Lower or no levels are present in the brain, heart, skeletal muscle, placenta and lung.

ADP/ATP translocase 4

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

Choline transporter

The high-affinity choline transporter (ChT) also known as solute carrier family 5 member 7 is a protein in humans that is encoded by the SLC5A7 gene. It is a cell membrane transporter and carries choline into acetylcholine-synthesizing neurons.

Mitochondrial 2-oxodicarboxylate carrier

Mitochondrial 2-oxodicarboxylate carrier also known as solute carrier family 25 member 21 (SLC25A21) is a protein that in humans is encoded by the SLC25A21 gene.

Mitochondrial fusion

Mitochondria are dynamic organelles with the ability to fuse and divide (fission), forming constantly changing tubular networks in most eukaryotic cells. These mitochondrial dynamics, first observed over a hundred years ago are important for the health of the cell, and defects in dynamics lead to genetic disorders. Through fusion, mitochondria can overcome the dangerous consequences of genetic malfunction. The process of mitochondrial fusion involves a variety of proteins that assist the cell throughout the series of events that form this process.

ADP/ATP translocase 2

ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.

Calcium-binding mitochondrial carrier protein SCaMC-1

Calcium-binding mitochondrial carrier protein SCaMC-1 is a protein that in humans is encoded by the SLC25A24 gene.

Solute carrier family 25 member 22

Solute carrier family 25 member 22 is a protein that in humans is encoded by the SLC25A22 gene. This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Expression of this gene is increased in colorectal tumor cells.

C19orf70

Chromosome 19 open reading frame 70, also known as QIL1, MICOS complex subunit MIC13 (MIC13) or Protein P117 is a protein that in humans is encoded by the C19orf70 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164209 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024259 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, et al. (August 2015). "Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder". Nature Genetics. 47 (8): 926–32. doi:10.1038/ng.3354. PMC   4520737 . PMID   26168012.
  6. 1 2 3 4 5 Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA (September 2016). "SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome". EMBO Molecular Medicine. 8 (9): 1019–38. doi:10.15252/emmm.201506159. PMC   5009808 . PMID   27390132.
  7. 1 2 "Entrez Gene: Solute carrier family 25 member 46" . Retrieved 2018-08-17.PD-icon.svgThis article incorporates text from this source, which is in the public domain.
  8. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
  9. "SLC25A46 - Solute carrier family 25 member 46". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  10. Online Mendelian Inheritance in Man (OMIM): solute carrier family 25, member 46; SLC25A46 - 610826
  11. 1 2 3 "SLC25A46 - Solute carrier family 25 member 46 - Homo sapiens (Human) - SLC25A46 gene & protein". www.uniprot.org. Retrieved 2018-08-16. CC-BY-icon-80x15.png  This article incorporates text available under the CC BY 4.0 license.
  12. 1 2 3 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC   5210571 . PMID   27899622.
  13. Palmieri F (April 2013). "The mitochondrial transporter family SLC25: identification, properties and physiopathology". Molecular Aspects of Medicine. 34 (2–3): 465–84. doi:10.1016/j.mam.2012.05.005. PMID   23266187.
  14. "SLC25A46 binary interactions found for search term SLC25A46". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-18.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.