Succinate dehydrogenase complex assembly factor 2, formerly known as SDH5 and also known as SDH assembly factor 2 or SDHAF2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that in humans is encoded by the SDHAF2

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene encodes a

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

protein needed for the flavination of a succinate dehydrogenase complex subunit required for activity of the complex.

Mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in this gene are associated with

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred ...

and

paraganglioma A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They a ...

Structure

''SDHAF2'' is located on the q arm of

Chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...

in position 12.2 and spans 16,642 base pairs. The ''SDHAF2'' gene produces a 6.7 kDa protein composed of 65 amino acids. This highly conserved protein is a cofactor of

flavin adenine dinucleotide Flavin may refer to: Placename * Flavin, Aveyron, a commune in southern France Surname * Adrian Flavin (born 1979), a professional rugby player * Christopher Flavin, president of the Worldwatch Institute * Dan Flavin (1933–1996), a minimali ...

(FAD). The structure represents a five-helix bundle with a region of well-defined conserved surface residues. This conserved region includes a negatively charged periphery and a positively charged surface, and a patch that is

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...

. The region is located in

α-helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

I, II, and the connecting band.

Function

The ''SDHAF2'' gene encodes a mitochondrial

associated with the succinate dehydrogenase (SDH) complex (mitochondrial complex II) in the mitochondrial respiratory chain, which plays essential roles in both the electron transport chain and the Krebs(tricarboxylic acid) cycle. SDHAF2 is integral in the proper function of the SDH complex, mainly in SDH-dependent respiration, and interacts with the catalytic subunit of the complex. SDHAF2 participates in the flavination of SDH1(SDHA), another subunit of the SDH complex. It does so by incorporating the

(FAD) cofactor into

SDHA Succinate dehydrogenase complex, subunit A, flavoprotein variant is a protein that in humans is encoded by the ''SDHA'' gene. This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial res ...

. Such flavination is required for a fully functional SDH complex. Knockdown of SDHAF2 leads to the loss-of-function of the SDH complex, a decrease in the enzyme complex stability, and a substantial reduction in all subunits. SDHAF2 was also found to function as a

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

Clinical significance

''SDHAF2'' is a

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

. Constitutional

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s in this gene cause

hereditary Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic infor ...

, a neuroendocrine tumor formerly known to be linked to SDH subunit mutations.

is a neural crest tumor usually derived from the

chemoreceptor A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecep ...

tissue of a paraganglion, and may develop at various body sites, including the head, neck,

thorax The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the ...

and

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the tors ...

. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the

jugular foramen A jugular foramen is one of the two (left and right) large foramina (openings) in the base of the skull, located behind the carotid canal. It is formed by the temporal bone and the occipital bone. It allows many structures to pass, including th ...

, the

vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and rig ...

, and in the

middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in ...

. Phenotypes include excessive

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol ( benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a ...

induced hypertension, dysfunction of major blood vessels and

cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

s, significant

morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that ...

sweating Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distri ...

, and

palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...

. In cases of extra-adrenal localization, the tumor may turn metastatic and aggressive. Loss of SDH complex function has been known to be responsible for

. Mutations in this gene are found in the DNA of only a small fraction of patients with the disease.

Interactions

SDHAF2 interacts with

within the SDH catalytic dimer. In addition to

, SDHAF2 has 17 protein-protein interactions, including interactions with proteins such as

IMMT Mitochondrial inner membrane protein is a protein that in humans is encoded by the ''IMMT'' gene.) ''IMMT'' encodes an inner mitochondrial membrane (IMM) protein in the nucleus. It is posttranslational transported to the IMM. Mic60/Mitofilin (e ...

SUCLG2 Succinyl-CoA ligase DP-formingsubunit beta, mitochondrial is an enzyme that in humans is encoded by the ''SUCLG2'' gene on chromosome 3. This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyze ...

, UBINEDDSUMO1,

SSX2IP Afadin- and alpha-actinin-binding protein is a protein that in humans is encoded by the ''SSX2IP'' gene. It has been shown that it functions together with WDR8 in centrosome maturation, ensuring proper spindle length and orientation. The SSX2IP-WD ...

, and others.

Structure

Function

Clinical significance

Interactions

References

Further reading