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NADH dehydrogenase biquinoneiron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''NDUFS2''
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 ba ...
. The
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, respo ...
encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (
complex I Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the Electron transport chain, respiratory chains of many organisms from bacteria to ...
). Mutations in this gene are associated with mitochondrial complex I deficiency.


Structure

''NDUFS2'' is located on the
q arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...
of
chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which ar ...
in position 23.3 and has 15
exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
s. The ''NDUFS2'' gene produces a 52.5 kDa protein composed of 463
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. NDUFS2, the protein encoded by this gene, is a member of the complex I 49 kDa subunit family. It is a
peripheral membrane protein Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the periph ...
on the
matrix Matrix most commonly refers to: * ''The Matrix'' (franchise), an American media franchise ** ''The Matrix'', a 1999 science-fiction action film ** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchis ...
side of the
inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...
. It contains a cofactor binding site for a nowiki/>4Fe-4S.html"_;"title="4Fe-4S.html"_;"title="nowiki/>4Fe-4S">nowiki/>4Fe-4S">4Fe-4S.html"_;"title="nowiki/>4Fe-4S">nowiki/>
nowiki/>4Fe-4S.html"_;"title="4Fe-4S.html"_;"title="nowiki/>4Fe-4S">nowiki/>4Fe-4S">4Fe-4S.html"_;"title="nowiki/>4Fe-4S">nowiki/>4Fe-4Scluster,_a_Signal_peptide">transit_peptide_ A_signal__peptide_(sometimes_referred_to_as_signal_sequence,_targeting_signal,_localization_signal,_localization_sequence,_transit_peptide,_leader_sequence_or_leader_peptide)_is_a_short_peptide_(usually_16-30_amino_acids_long)_present_at_the_N-ter_...
,_5_turns,_11_Beta_sheet.html" "title="4Fe-4Scluster,_a_Signal_peptide.html" "title="4Fe-4S">nowiki/>4Fe-4S.html" ;"title="4Fe-4S.html" ;"title="nowiki/>4Fe-4S">nowiki/>4Fe-4S">4Fe-4S.html" ;"title="nowiki/>4Fe-4S">nowiki/>4Fe-4Scluster, a Signal peptide">transit peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
, 5 turns, 11 Beta sheet">beta strands Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labio ...
, and 18 alpha helixes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.


Function

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 use ...
complex I Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the Electron transport chain, respiratory chains of many organisms from bacteria to ...
is the first multimeric complex of the
respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
that catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mammalian mitochondrial complex I is an assembly of at least 43 different subunits. Seven of the subunits are encoded by the
mitochondrial genome Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...
; the remainder are the products of nuclear genes. The
iron-sulfur protein Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur clu ...
(IP) fraction of complex I is made up of 7 subunits, including NDUFS2. Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to the stabilization of the early intermediate complex.


Clinical significance

Mutations in the ''NDUFS2'' gene are associated with Mitochondrial Complex I Deficiency, which is
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
. This deficiency is the most common enzymatic defect of the
oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine tri ...
disorders. Mitochondrial complex I deficiency shows extreme
genetic heterogeneity Genetic heterogeneity occurs through the production of single or similar phenotypes through different genetic mechanisms. There are two types of genetic heterogeneity: allelic heterogeneity, which occurs when a similar phenotype is produced by diffe ...
and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible. However, the majority of cases are caused by mutations in nuclear-encoded genes. It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders.
Phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
s include
macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...
with progressive
leukodystrophy Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". Th ...
, nonspecific
encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
,
hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
,
myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
,
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...
,
Leigh syndrome Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who fir ...
,
Leber hereditary optic neuropathy Leber's hereditary optic neuropathy (LHON) is a Human mitochondrial genetics, mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss o ...
, and some forms of
Parkinson disease Parkinson may refer to: *Parkinson (surname) * ''Parkinson'' (TV series), British chat show, presented by Sir Michael Parkinson *Parkinson, Queensland, suburb of Brisbane, Australia *The Parkinsons (fl. early 20th century), American father-and-son ...
.


Interactions

NDUFS2 has been shown to have 121 binary protein-protein interactions including 112 co-complex interactions. NDUFS2 appears to interact with
NDUFS3 NADH dehydrogenase biquinoneiron-sulfur protein 3, mitochondrial is an enzyme that in humans is encoded by the ''NDUFS3'' gene on chromosome 11. This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone ox ...
,
MKLN1 Muskelin is a protein that in humans is encoded by the ''MKLN1'' gene. Interactions MKLN1 has been shown to interact with RANBP9 Ran-binding protein 9 is a protein that in humans is encoded by the ''RANBP9'' gene. Function This gene encodes ...
,
EGR2 Early growth response protein 2 is a protein that in humans is encoded by the ''EGR2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation ...
,
HMOX2 Heme oxygenase 2 is an enzyme that in humans is encoded by the ''HMOX2'' gene. Function Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reducta ...
, CENPU, and
TNFRSF14 Herpesvirus entry mediator (HVEM), also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a human cell surface receptor of the TNF-receptor superfamily. Nomenclature This protein was originally known as herpesvirus entr ...
.


See also

*
NDUFS1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the ''NDUFS1'' gene. The encoded protein, NDUFS1, is the largest subunit of complex I, located on the inner mitochondrial membrane, and ...


References


Further reading

* * * * * * * * * * * * {{Enzymes Human proteins EC 1.6.5 EC 1.6.99