Langbahn Team – Weltmeisterschaft

SLC25A46

SLC25A46
Identifiers
AliasesSLC25A46, HMSN6B, solute carrier family 25 member 46, PCH1E
External IDsOMIM: 610826; MGI: 1914703; HomoloGene: 14518; GeneCards: SLC25A46; OMA:SLC25A46 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

91137

67453

Ensembl

ENSG00000164209

ENSMUSG00000024259

UniProt

Q96AG3

Q9CQS4

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 MbChr 18: 31.69 – 31.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164209 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b c 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. ^ a b c d e 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. ^ a b "Entrez Gene: Solute carrier family 25 member 46". Retrieved 2018-08-17.Public Domain This 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).[permanent dead link‍]
  10. ^ Online Mendelian Inheritance in Man (OMIM): solute carrier family 25, member 46; SLC25A46 - 610826
  11. ^ a b c "SLC25A46 - Solute carrier family 25 member 46 - Homo sapiens (Human) - SLC25A46 gene & protein". www.uniprot.org. Retrieved 2018-08-16. This article incorporates text available under the CC BY 4.0 license.
  12. ^ a b c "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.

Quelle: https://en.wikipedia.org/wiki/SLC25A46