Persius/hicric huggingface dataset:
NDUFB8
NADH dehydrogenase  1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

# Gene
The NDUFB8 gene is located on the q arm of chromosome 10 in position 24.31 and is 6,194 base pairs long.

# Structure
The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids. NDUFB8 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.

# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.

# Model organisms
Model organisms have been used in the study of NDUFB8 function. A conditional knockout mouse line called Ndufb8tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
NDUFB9
NADH dehydrogenase  1 beta subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFB9 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

# Structure
The NDUFB9 gene is located on the q arm of chromosome 8 in position 13.3 and is 10,884 base pairs long. The NDUFB9 protein weighs 22 kDa and is composed of 179 amino acids. NDUFB9 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.

# Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.

# Clinical significance
A mutation in NDUFB9 resulting in reduction in NDUFB9 protein and both amount and activity of complex I has been shown to be a causal mutation leading to Complex I deficiency.
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 is important for mitochondrial oxidative phosphorylation. Mutations in this gene are associated with complex I deficiency.

# Structure
NDUFS1 is located on the q arm of chromosome 2 in position 33.3 and has 20 exons. The NDUFS1 gene produces a 79.5 kDa protein composed of 727 amino acids. NDUFS1, the protein encoded by this gene, is a member of the complex I 75 kDa subunit family. It contains a transit peptide, 10 turns, 19 beta strands, 27 alpha helixes, and cofactor binding sites for  and  clusters. The cluster domains consist of a 79 amino acid 2Fe-2S ferredoxin-type from positions 30-108, a 40 amino acid 4Fe-4S His(Cys)3-ligated-type from positions 108-147, and a 57 amino acid 4Fe-4S Mo/W bis-MGD-type from positions 245-301. Several transcript variants encoding different isoforms have been found for this gene.

# Function
The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized.

# Clinical significance
Mutations in the NDUFS1 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. Mitochondrial complex I deficiency shows extreme genetic heterogeneity 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. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.

# Interactions
NDUFS1 has been shown to have 124 binary protein-protein interactions including 110 co-complex interactions. NDUFS1 appears to interact with SOAT1, NDUFA9, HLA-B, ECE2, C1QTNF9, GPAA1, STOM, GDI1, ACAP2, EHBP1, MBOAT7, PIGS.
NDUFS2
NADH dehydrogenase  iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mutations in this gene are associated with mitochondrial complex I deficiency.

# Structure
NDUFS2 is located on the q arm of chromosome 1 in position 23.3 and has 15 exons. The NDUFS2 gene produces a 52.5 kDa protein composed of 463 amino acids. NDUFS2, the protein encoded by this gene, is a member of the complex I 49 kDa subunit family. It is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane. It contains a cofactor binding site for a  cluster, a transit peptide, 5 turns, 11 beta strands, and 18 alpha helixes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

# Function
Mitochondrial complex I is the first multimeric complex of the respiratory chain 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; the remainder are the products of nuclear genes. The iron-sulfur protein (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. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. Mitochondrial complex I deficiency shows extreme genetic heterogeneity 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. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.

# Interactions
NDUFS2 has been shown to have 121 binary protein-protein interactions including 112 co-complex interactions. NDUFS2 appears to interact with NDUFS3, MKLN1, EGR2, HMOX2, CENPU, and TNFRSF14.
NDUFS6
NADH dehydrogenase  iron-sulfur protein 6, mitochondrial is an enzyme that in humans is encoded by the NDUFS6 gene.

# Function
The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the electron transport chain of mitochondria. The iron-sulfur protein (IP) fraction is made up of 7 subunits, including NDUFS6.

# Clinical significance
Mutations in the NDUFS6 gene are associated with mitochondrial Complex I deficiency, and are inherited in an autosomal recessive manner. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. Mitochondrial complex I deficiency shows extreme genetic heterogeneity 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. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
In NDUFS6 mutations the presentation is typically a neonatal lactic acidosis that is swiftly fatal, coupled with multi-system failure.
NDUFS7
NADH dehydrogenase  iron-sulfur protein 7, mitochondrial, also knowns as NADH-ubiquinone oxidoreductase 20 kDa subunit, Complex I-20kD (CI-20kD), or PSST subunit is an enzyme that in humans is encoded by the NDUFS7 gene. The NDUFS7 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

# Structure
The NDUFS7 gene is located on the p arm of chromosome 19 in position 13.3. The NDUFS7 gene produces a 25 kDa protein composed of 238 amino acids. The PSST subunit is highly conserved across evolutionary distances. Crystal structures and mutational studies indicate that it is one of the ubiquinone binding sites of Complex I, together with the TYKY (NDUFS8) subunit. It has been proposed that PSST, along with TYKY, 49 kDa, ND1 and ND5 subunits interact with iron-sulfur clusters as part of the catalytic core of NADH dehydrogenase (ubiquinone).

# Function
The PSST subunit encoded by the NDUSF7 gene is one of over 40 subunits involved in the transfer of electrons from NADH to ubiquinone. Specifically, it is thought that the PSST subunit directly couples electron transfer between the iron-sulfur cluster N2 and ubiquinone, along with ubiquinone-binding ND1. Functional evidence for the importance of PSST has been garnered from mutational studies in the obligate aerobic yeast, Yarrow lipolytic, which elucidated a central role in proton translocation that was reduced in mutant forms of the subunit.

# Clinical Significance
Mitochondrial complex I deficiency (MT-C1D) is caused by mutations affecting the NDUFS7 gene. Complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations, from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease. Leigh syndrome is an early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord, and is the most common mitochondrial encephalomyopathy. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, dysphagia, and lactic acidosis.

# Interactions
In addition to co-subunits for complex I, NDUFS7 has protein-protein interactions with ENO2 and ARRB2.
NDUFV1
NADH dehydrogenase  flavoprotein 1, mitochondrial (NDUFV1) is an enzyme that in humans is encoded by the NDUFV1 gene. The NDUFV1 gene encodes the 51-kD subunit of complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain. Defects in complex I are a common cause of mitochondrial dysfunction. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome.

# Structure
NDUFV1 is located on the q arm of chromosome 11 in position 13.2 and has 10 exons. The NDUFV1 gene produces a 50.8 kDa protein composed of 464 amino acids. NDUFV1, the protein encoded by this gene, is a member of the complex I 51 kDa subunit family. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-binding sites. It also contains a transit peptide domain and is composed of 6 turns, 14 beta strands, and 19 alpha helixes.

# Function
Complex I is composed of 45 different subunits. NDUFV1 is a component of the flavoprotein-sulfur (FP) fragment of the enzyme. NDUFV1 is an oxidoreductase and core subunit of complex I that is thought to be required for assembly and catalysis. It is a peripheral membrane protein located on the matrix side of the mitochondrion inner membrane.

## Catalytic Activity
NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).
NADH + acceptor = NAD+ + reduced acceptor.

# Clinical significance
Mutations in the NDUFV1 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. Mitochondrial complex I deficiency shows extreme genetic heterogeneity 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. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Clinical manifestations can include lactic acidosis, cerebral degeneration, ophthalmoplegia, ataxia, spasticity, and dystonia resulting from mutations in NDUFV1.

# Interactions
NDUFV1 has been shown to have 103 binary protein-protein interactions including 97 co-complex interactions. NDUFV1 appears to interact with EWSR1, CREB1, NCOR1, and VDAC1.
NDUFV2
NADH dehydrogenase  flavoprotein 2, mitochondrial (NDUFV2) is an enzyme that in humans is encoded by the NDUFV2 gene. The encoded protein, NDUFV2, is a subunit of complex I of the mitochondrial respiratory chain, which is located on the inner mitochondrial membrane and involved in oxidative phosphorylation. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy.

# Structure
NDUFV2 is located on the p arm of chromosome 18 in position 11.22 and has 9 exons. The NDUFV2 gene produces a 27.4 kDa protein composed of 249 amino acids. NDUFV2, the protein encoded by this gene, is a member of the complex I 24 kDa subunit family. It contains a cofactor binding site for a 2Fe-2S cluster and a transit peptide domain. The protein consists of 2 turns, 3 beta strands, and 7 alpha helixes. A non-transcribed pseudogene of this locus is found on chromosome 19.

# Function
The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes the 24 kDa subunit of complex I, and is involved in electron transfer. NDUFV2 is an oxidoreductase and a component of the flavoprotein-sulfur (FP) fragment of the enzyme. It is thought to be required for assembly and catalysis.

## Catalytic activity
NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).
NADH + acceptor = NAD+ + reduced acceptor.

# Clinical significance
Mutations in the NDUFV2 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. Mitochondrial complex I deficiency shows extreme genetic heterogeneity 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. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.

# Interactions
NDUFV2 has been shown to have 102 binary protein-protein interactions including 80 co-complex interactions. NDUFV2 appears to interact with HSCB, CCNC, GOLM1, FAM114A2, CRMP1, KAT5, SP110.
NFATC2
Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.

# Function
This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

# Clinical significance
NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed, NFAT1 (NFATC2) is pro-invasive and pro-migratory in breast carcinoma.
To increase cell motility NFAT1 up-regulates the gene of the Lipocalin 2 expression and modulate the TWEAKR/TWEAK axis.
Translocation forming an in frame fusions product between EWSR1 gene and the NFATc2 gene has been described in bone tumor with a Ewing sarcoma-like clinical appearance. The translocation breakpoint led to the loss of the controlling elements of the NFATc2 protein and the fusion of the N terminal region of the EWSR1 gene conferred constant activation of the protein.

# Interactions
NFATC2 has been shown to interact with MEF2D, EP300, IRF4 and Protein kinase M.
NFATC4
Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene.

# Function
The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4.
NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed, NFAT3 (NFATc4) is an inhibitor of cell motility by blocking the expression of LCN2.

# Interactions
NFATC4 has been shown to interact with CREB-binding protein.