SLC25A3

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 Inner mitochondrial membrane, mitochondrial inner membrane and Catalysis, catalyzes the Membrane transport, transport of Phosphate#Biochemistry of phosphates, phosphate ions across it for the purpose of Oxidative phosphorylation#Eukaryotic electron transport chains, oxidative phosphorylation. There are two significant Protein isoform, isoforms of this gene Gene expression, expressed in human cells, which differ slightly in Protein structure, structure and function. Mutations in this gene can cause Mitochondrial carrier, mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, Neonatal nursing, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.

Structure

The ''SLC25A3'' gene is located on the q arm of chromosome 12 in position 23.1 and spans 8,376 base pairs. The gene has 9 exons and produces a 40.1 kDa protein composed of 362 amino acids. The encoded protein (PHC) is a Integral membrane protein#Integral polytopic protein, multi-pass transmembrane protein located in the mitochondrial inner membrane; it contains six transmembrane segments, emerging into a large extramembranous loop. Both the N-terminus, N-terminal and C-terminus, C-terminal regions of this protein protrude toward the cytosol. PHC contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier protein family, family. There exist two transcript variants of this protein, PHC-A and PHC-B, which differ by 13 amino acids. Isoform A contains 42 amino acids while Isoform B contains 41. In vitro, the isoforms differ in their substrate affinities and transport rates.

Function

The encoded protein (PHC) catalyzes the transport of phosphate from the cytosol into the mitochondrial matrix, either by proton Cotransporter, cotransport or Antiporter, in exchange for Hydroxide, hydroxyl ions. In the final steps of oxidative phosphorylation, this protein catalyzes the uptake of a phosphate ion with a proton across the mitochondrial inner membrane. The availability of inorganic phosphate for oxidative phosphorylation is mainly dependent on PHC activity. To substantially affect oxidative phosphorylation, PHC depletion must be severe, exceeding 85%. This protein may be involved in regulation of the mitochondrial permeability transition pore (mPTP).

Clinical significance

Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation. Symptoms include lactic acidosis, hypertrophic cardiomyopathy, and neonatal hypotonia; afflicted patients die within the first year of life.

Isoform A of this gene is expressed at high levels in Cardiac muscle cell, heart, pancrease, pancreatic, and skeletal muscle cells while Isoform B is expressed in all tissues, albeit poorly.

In the sole recorded case of a mutation in this gene, a Zygosity#Homozygous, homozygous mutation (c.215G>A) in the Alternative splicing, alternatively spliced exon 3A of this gene caused an amino acid replacement (G72E) in Isoform A. This leads to ATP synthase deficiency in Myocyte, muscle cells, which express Isoform A, but not in fibroblasts, which express Isoform B, causing MPCD and the aforementioned standard symptoms.

Interactions

The encoded protein protein-protein interactions, interacts with PPIF; this interaction is impaired by ERCC8 (gene), CsA.

See also

* Solute carrier family

References

Further reading

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{{Membrane transport proteins

Solute carrier family