Annotations: 6VAX

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Succ_DH_flav_C	e6vaxA1	A: alpha bundles	X: Spectrin repeat-like	H: Succinate dehydrogenase/fumarate reductase flavoprotein C-terminal domain (From Topology)	T: Succinate dehydrogenase/fumarate reductase flavoprotein C-terminal domain	F: Succ_DH_flav_C	ECOD (1.6)
A	FAD_binding_2	e6vaxA3	A: a+b complex topology	X: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain (From Topology)	H: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain (From Topology)	T: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain	F: FAD_binding_2	ECOD (1.6)
A	FAD_binding_3_1st	e6vaxA2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: FAD_binding_3_1st	ECOD (1.6)
C	Succ_DH_flav_C	e6vaxC1	A: alpha bundles	X: Spectrin repeat-like	H: Succinate dehydrogenase/fumarate reductase flavoprotein C-terminal domain (From Topology)	T: Succinate dehydrogenase/fumarate reductase flavoprotein C-terminal domain	F: Succ_DH_flav_C	ECOD (1.6)
C	FAD_binding_2	e6vaxC3	A: a+b complex topology	X: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain (From Topology)	H: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain (From Topology)	T: Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain	F: FAD_binding_2	ECOD (1.6)
C	FAD_binding_3_1st	e6vaxC2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: FAD/NAD(P)-binding domain	F: FAD_binding_3_1st	ECOD (1.6)
D	Sdh5	e6vaxD1	A: alpha arrays	X: YgfY-like (DUP399, Pfam03937) (From Topology)	H: YgfY-like (DUP399, Pfam03937) (From Topology)	T: YgfY-like (DUP399, Pfam03937)	F: Sdh5	ECOD (1.6)
B	Sdh5	e6vaxB1	A: alpha arrays	X: YgfY-like (DUP399, Pfam03937) (From Topology)	H: YgfY-like (DUP399, Pfam03937) (From Topology)	T: YgfY-like (DUP399, Pfam03937)	F: Sdh5	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF02910	Fumarate reductase flavoprotein C-term (Succ_DH_flav_C)	Fumarate reductase flavoprotein C-term	This family contains fumarate reductases, succinate dehydrogenases and L-aspartate oxidases.	Domain
A, C	PF00890	FAD binding domain (FAD_binding_2)	FAD binding domain	-	Family
B, D	PF03937	Flavinator of succinate dehydrogenase (Sdh5)	Flavinator of succinate dehydrogenase	This family includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE. Both yeast and human Sdh5/SDHAF2 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron trans ...	This family includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE. Both yeast and human Sdh5/SDHAF2 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Mutational inactivation of Sdh5 confers tumor susceptibility in humans [1]. Bacterial homologues of Sdh5, termed SdhE, are functionally conserved being required for the flavinylation of SdhA and succinate dehydrogenase activity. Like Sdh5, SdhE interacts with SdhA. Furthermore, SdhE was characterised as a FAD co-factor chaperone that directly binds FAD to facilitate the flavinylation of SdhA. Phylogenetic analysis demonstrates that SdhE/Sdh5 proteins evolved only once in an ancestral alpha-proteobacteria prior to the evolution of the mitochondria and now remain in subsequent descendants including eukaryotic mitochondria and the alpha, beta and gamma proteobacteria [2]. This family was previously annotated in Pfam as being a divergent TPR repeat but structural evidence has indicated this is not true. The E. coli protein, YgfY also acts as the antitoxin to the membrane-bound toxin family Cpta, Pfam:PF13166, whose E. coli member YgfX, expressed from the same operon as YgfY [3].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	flavin adenine dinucleotide binding binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding nucleotide binding heterocyclic compound binding small molecule binding oxidoreductase activity succinate dehydrogenase activity oxidoreductase activity, acting on the CH-CH group of donors oxidoreductase activity, acting on the CH-CH group of donors, quinone or related compound as acceptor catalytic activity flavin adenine dinucleotide binding binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding nucleotide binding heterocyclic compound binding small molecule binding oxidoreductase activity succinate dehydrogenase activity oxidoreductase activity, acting on the CH-CH group of donors oxidoreductase activity, acting on the CH-CH group of donors, quinone or related compound as acceptor catalytic activity succinate dehydrogenase (quinone) activity electron transfer activity	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds metabolic process cellular process primary metabolic process generation of precursor metabolites and energy ribose phosphate metabolic process oxidative phosphorylation ATP metabolic process ATP biosynthetic process nucleotide biosynthetic process carbohydrate derivative metabolic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds metabolic process cellular process primary metabolic process generation of precursor metabolites and energy ribose phosphate metabolic process oxidative phosphorylation ATP metabolic process ATP biosynthetic process nucleotide biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process purine ribonucleoside triphosphate biosynthetic process proton motive force-driven ATP synthesis nucleobase-containing compound metabolic process ribonucleotide biosynthetic process purine nucleotide metabolic process ribonucleotide metabolic process purine nucleoside triphosphate biosynthetic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process purine ribonucleoside triphosphate metabolic process phosphate-containing compound metabolic process small molecule metabolic process phosphorus metabolic process ribose phosphate biosynthetic process ribonucleoside triphosphate metabolic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process purine nucleoside triphosphate metabolic process nucleoside triphosphate biosynthetic process nucleotide metabolic process nucleobase-containing compound biosynthetic process ribonucleoside triphosphate biosynthetic process purine-containing compound metabolic process biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process proton motive force-driven mitochondrial ATP synthesis nucleoside triphosphate metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process mitochondrial electron transport, succinate to ubiquinone aerobic electron transport chain ATP synthesis coupled electron transport electron transport chain respiratory electron transport chain mitochondrial ATP synthesis coupled electron transport developmental process multicellular organism development multicellular organismal process anatomical structure development nervous system development system development succinate metabolic process oxoacid metabolic process dicarboxylic acid metabolic process carboxylic acid metabolic process organic acid metabolic process	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope organelle membrane nucleus membrane-enclosed lumen intracellular membraneless organelle nucleolus intracellular organelle lumen organelle lumen membraneless organelle nuclear lumen respiratory chain complex protein-containing complex catalytic complex respiratory chain complex II (succinate dehydrogenase) membrane protein complex oxidoreductase complex mitochondrial matrix
B, D	Succinate dehydrogenase assembly factor 2, mitochondrial	-	protein-FAD linkage macromolecule modification metabolic process cellular process primary metabolic process protein metabolic process macromolecule metabolic process protein modification process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds generation of precursor metabolites and energy mitochondrial electron transport, succinate to ubiquinone protein-FAD linkage macromolecule modification metabolic process cellular process primary metabolic process protein metabolic process macromolecule metabolic process protein modification process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds generation of precursor metabolites and energy mitochondrial electron transport, succinate to ubiquinone aerobic electron transport chain oxidative phosphorylation ATP synthesis coupled electron transport electron transport chain respiratory electron transport chain mitochondrial ATP synthesis coupled electron transport regulation of epithelial to mesenchymal transition multicellular organismal process regulation of cellular process regulation of developmental process cellular developmental process negative regulation of biological process regulation of cell differentiation mesenchyme development cell differentiation anatomical structure development negative regulation of cellular process negative regulation of cell differentiation regulation of multicellular organismal process developmental process regulation of biological process negative regulation of developmental process biological regulation animal organ development tissue development negative regulation of epithelial to mesenchymal transition epithelial to mesenchymal transition mesenchymal cell differentiation negative regulation of multicellular organismal process protein dephosphorylation dephosphorylation phosphate-containing compound metabolic process phosphorus metabolic process cellular response to stimulus response to stimulus signaling negative regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway regulation of signal transduction negative regulation of cell communication cell communication negative regulation of Wnt signaling pathway signal transduction Wnt signaling pathway regulation of signaling cell surface receptor signaling pathway regulation of Wnt signaling pathway negative regulation of response to stimulus negative regulation of signal transduction negative regulation of canonical Wnt signaling pathway regulation of response to stimulus regulation of cell communication protein-containing complex organization mitochondrial respirasome assembly cellular component organization cellular component biogenesis organelle organization cellular component assembly mitochondrial respiratory chain complex assembly protein-containing complex assembly mitochondrial respiratory chain complex II assembly cellular component organization or biogenesis respiratory chain complex II assembly mitochondrion organization	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membraneless organelle nucleolus intracellular organelle lumen organelle lumen membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membraneless organelle nucleolus intracellular organelle lumen organelle lumen membraneless organelle nuclear lumen cytosol mitochondrial matrix

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C	IPR015939	Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal	Domain
A, C	IPR003952	Fumarate reductase/succinate dehydrogenase, FAD-binding site	Binding Site
A, C	IPR037099	Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal domain superfamily	Homologous Superfamily
A, C	IPR036188	FAD/NAD(P)-binding domain superfamily	Homologous Superfamily
A, C	IPR003953	FAD-dependent oxidoreductase 2, FAD binding domain	Domain
A, C	IPR030664	FAD-dependent oxidoreductase SdhA/FrdA/AprA	Family
A, C	IPR027477	Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain superfamily	Homologous Superfamily
A, C	IPR014006	Succinate dehydrogenase/fumarate reductase, flavoprotein subunit	Family
A, C	IPR011281	Succinate dehydrogenase, flavoprotein subunit	Family
B, D	IPR036714	Flavinator of succinate dehydrogenase superfamily	Homologous Superfamily
B, D	IPR028882	Succinate dehydrogenase assembly factor 2, mitochondrial	Family
B, D	IPR005631	Flavinator of succinate dehydrogenase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C	Pharos: P31040	Leigh syndrome gastrointestinal stromal tumor mitochondrial complex II deficiency, nuclear type 1 paraganglioma dilated cardiomyopathy paragangliomas 5 dilated cardiomyopathy 1GG cardiomyopathy LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY neuroendocrine carcinoma adrenal medulla cancer cancer left ventricular noncompaction osteoarthritis benign neoplasm of adrenal gland Leigh syndrome gastrointestinal stromal tumor mitochondrial complex II deficiency, nuclear type 1 paraganglioma dilated cardiomyopathy paragangliomas 5 dilated cardiomyopathy 1GG cardiomyopathy LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY neuroendocrine carcinoma adrenal medulla cancer cancer left ventricular noncompaction osteoarthritis benign neoplasm of adrenal gland phaeochromocytoma familial dilated cardiomyopathy inborn errors of metabolism leukodystrophy neurodegenerative disease osteoarthritis susceptibility 1 Carney triad schizophrenia dilated cardiomyopathy 1A familial isolated dilated cardiomyopathy intellectual disability
B, D	Pharos: Q9NX18	Wilson disease paragangliomas 2 adrenal medulla cancer cancer hypertensive disorder neuroendocrine carcinoma PARAGANGLIOMAS 2 (disorder) benign neoplasm of adrenal gland heart disease paraganglioma phaeochromocytoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.