SURF1 is located on the q arm of chromosome 9 in position 34.2 and has 9 exons. The SURF1 gene produces a 33.3 kDa protein composed of 300 amino acids. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeitgene cluster, a group of very tightlylinked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. SURF1 is a multi-pass protein that contains two transmembrane regions, one 19 amino acids in length from positions 61-79 and the other 17 amino acids in length from positions 274-290.
Function
This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. SURF1 is a multi-pass membrane protein component of the mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex. The MITRAC complex regulates cytochrome c oxidase assembly by acting as a central assembly intermediate, receiving subunits imported to the inner mitochondrial membrane and regulating COX1mRNA translation.
Clinical significance
Mutations in SURF1 have been associated with mitochondrial complex IV deficiency with clinical manifestations of Leigh syndrome and Charcot-Marie-Tooth disease 4K.
Charcot-Marie-Tooth disease 4K is an autosomal recessive, demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities, segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention, autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4K patients manifest upper and lower limbs involvement. Some affected individuals have nystagmus, polyneuropathy, putaminal and periaqueductal lesions, and late-onset cerebellar ataxia. This disease, when associated with mutations in SURF1, has been found to be linked to cytochrome c oxidase deficiency. Variants associated with this CMT4K have included a homozygous splice site mutation, c.107-2A>G, a missense mutation, c.574C>T, and a deletion, c.799_800del.
Interactions
SURF1 has been shown to have 11 binary protein-protein interactions including 8 co-complex interactions. SURF1 interacts with COA3 as part of the mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex. PTGES3, SLC25A5, COX6C, COX14, COA1 have all also been found to interact with SURF1.