6WIH

N-terminal mutation of ISCU2 (L35H36) traps Nfs1 Cys loop in the active site of ISCU2 without metal present. Structure of human mitochondrial complex Nfs1-ISCU2(L35H36)-ISD11 with E.coli ACP1 at 1.9 A resolution (NIAU)2.

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
D	d6wihd1	Alpha and beta proteins (a+b)	SufE/NifU	SufE/NifU	NifU/IscU domain	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d6wihd2	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d6wiha1	Alpha and beta proteins (a/b)	PLP-dependent transferase-like	PLP-dependent transferases	Cystathionine synthase-like	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d6wiha2	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d6wihb_	Membrane and cell surface proteins and peptides	LYR proteins from mammalian respiratory complex I	LYR protein-like	LYR proteins	LYR motif-containing protein 4	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d6wihc_	All alpha proteins	Acyl carrier protein-like	ACP-like	Acyl-carrier protein (ACP)	Acyl carrier protein	(Escherichia coli ) [TaxId: 562 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	PLP-dependent transferases	8074674	3000954	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	ACP-like	8040084	3001805	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
D	NifU_N	e6wihD1	A: a+b two layers	X: FAD-linked reductases, C-terminal domain-like	H: SufE/NifU (From Topology)	T: SufE/NifU	F: NifU_N	ECOD (1.6)
A	Aminotran_5_C	e6wihA1	A: a+b two layers	X: C-terminal domain in some PLP-dependent transferases (From Topology)	H: C-terminal domain in some PLP-dependent transferases (From Topology)	T: C-terminal domain in some PLP-dependent transferases	F: Aminotran_5_C	ECOD (1.6)
A	Aminotran_5_N	e6wihA2	A: a/b three-layered sandwiches	X: PLP-dependent transferases (From Topology)	H: PLP-dependent transferases (From Topology)	T: PLP-dependent transferases	F: Aminotran_5_N	ECOD (1.6)
B	Complex1_LYR	e6wihB1	A: alpha bundles	X: LYR protein (From Topology)	H: LYR protein (From Topology)	T: LYR protein	F: Complex1_LYR	ECOD (1.6)
C	PP-binding	e6wihC1	A: alpha bundles	X: ACP-like	H: Acyl-carrier protein (ACP) (From Topology)	T: Acyl-carrier protein (ACP)	F: PP-binding	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D	3.90.1010.10	Alpha Beta	Alpha-Beta Complex	Sufe protein. Chain: A		CATH (utative)
A	3.40.640.10	Alpha Beta	3-Layer(aba) Sandwich	Aspartate Aminotransferase	domain 2	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
D	PF01592	NifU-like N terminal domain (NifU_N)	NifU-like N terminal domain	-	Family
A	PF00266	Aminotransferase class-V (Aminotran_5)	Aminotransferase class-V	This domain is found in amino transferases, and other enzymes including cysteine desulphurase EC:4.4.1.-.	Domain
B	PF05347	Complex 1 protein (LYR family) (Complex1_LYR)	Complex 1 protein (LYR family)	-	Family
C	PF00550	Phosphopantetheine attachment site (PP-binding)	Phosphopantetheine attachment site	A 4'-phosphopantetheine prosthetic group is attached through a serine. This prosthetic group acts as a a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups. This domain forms a four helix bundle. This family includes memb ...	A 4'-phosphopantetheine prosthetic group is attached through a serine. This prosthetic group acts as a a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups. This domain forms a four helix bundle. This family includes members not included in Prosite. The inclusion of these members is supported by sequence analysis and functional evidence. The related domain of Swiss:P19828 has the attachment serine replaced by an alanine.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
D	Iron-sulfur cluster assembly enzyme ISCU, mitochondrial	cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity iron-sulfur cluster binding 2 iron, 2 sulfur cluster binding cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity iron-sulfur cluster binding 2 iron, 2 sulfur cluster binding metal cluster binding molecular adaptor activity zinc ion binding	intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis regulation of lyase activity regulation of molecular function positive regulation of molecular function regulation of catalytic activity intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis regulation of lyase activity regulation of molecular function positive regulation of molecular function regulation of catalytic activity biological regulation positive regulation of catalytic activity positive regulation of aconitate hydratase activity regulation of aconitate hydratase activity positive regulation of lyase activity regulation of localization regulation of cellular process iron import into cell negative regulation of biological process negative regulation of iron ion transmembrane transport negative regulation of transport localization establishment of localization in cell negative regulation of cation transmembrane transport monoatomic cation transport regulation of biological process import across plasma membrane regulation of monoatomic ion transport iron ion transport iron ion transmembrane transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport negative regulation of iron ion import across plasma membrane transmembrane transport regulation of transmembrane transport import into cell cellular localization transport monoatomic ion transmembrane transport negative regulation of monoatomic ion transport regulation of monoatomic ion transmembrane transport metal ion transport negative regulation of transmembrane transport monoatomic cation transmembrane transport regulation of iron ion transmembrane transport negative regulation of monoatomic ion transmembrane transport negative regulation of cellular process monoatomic ion transport regulation of metal ion transport regulation of iron ion import across plasma membrane iron ion import across plasma membrane negative regulation of iron ion transport regulation of transport regulation of iron ion transport inorganic cation import across plasma membrane regulation of cellular localization inorganic ion import across plasma membrane transition metal ion transport cellular process regulation of monoatomic cation transmembrane transport cellular component biogenesis cellular component organization metallo-sulfur cluster assembly cellular component assembly iron-sulfur cluster assembly cellular component organization or biogenesis aerobic respiration cellular respiration aerobic electron transport chain oxidative phosphorylation energy derivation by oxidation of organic compounds ATP synthesis coupled electron transport positive regulation of biological process electron transport chain regulation of generation of precursor metabolites and energy regulation of cellular respiration positive regulation of cellular respiration positive regulation of metabolic process respiratory electron transport chain positive regulation of cellular process generation of precursor metabolites and energy mitochondrial electron transport, NADH to ubiquinone regulation of aerobic respiration regulation of mitochondrial electron transport, NADH to ubiquinone positive regulation of mitochondrial electron transport, NADH to ubiquinone metabolic process regulation of metabolic process mitochondrial ATP synthesis coupled electron transport [2Fe-2S] cluster assembly [4Fe-4S] cluster assembly	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex transferase complex L-cysteine desulfurase complex mitochondrial [2Fe-2S] assembly complex membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen nucleus
A	Cysteine desulfurase, mitochondrial	cysteine desulfurase activity sulfurtransferase activity transferase activity, transferring sulphur-containing groups transferase activity catalytic activity iron-sulfur cluster binding binding metal cluster binding small molecule binding vitamin binding vitamin B6 binding pyridoxal phosphate binding ion binding organic cyclic compound binding cysteine desulfurase activity sulfurtransferase activity transferase activity, transferring sulphur-containing groups transferase activity catalytic activity iron-sulfur cluster binding binding metal cluster binding small molecule binding vitamin binding vitamin B6 binding pyridoxal phosphate binding ion binding organic cyclic compound binding anion binding heterocyclic compound binding identical protein binding protein binding protein homodimerization activity protein dimerization activity cation binding metal ion binding	cellular component biogenesis cellular component organization metallo-sulfur cluster assembly cellular component assembly iron-sulfur cluster assembly cellular process cellular component organization or biogenesis organophosphate metabolic process molybdopterin cofactor metabolic process phosphate-containing compound metabolic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process cellular component biogenesis cellular component organization metallo-sulfur cluster assembly cellular component assembly iron-sulfur cluster assembly cellular process cellular component organization or biogenesis organophosphate metabolic process molybdopterin cofactor metabolic process phosphate-containing compound metabolic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process phosphorus metabolic process prosthetic group metabolic process [4Fe-4S] cluster assembly iron incorporation into metallo-sulfur cluster metal incorporation into metallo-sulfur cluster macromolecule modification protein modification process Mo-molybdopterin cofactor biosynthetic process Mo-molybdopterin cofactor metabolic process molybdopterin cofactor biosynthetic process biosynthetic process organophosphate biosynthetic process [2Fe-2S] cluster assembly	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex transferase complex L-cysteine desulfurase complex mitochondrial [2Fe-2S] assembly complex centrosome microtubule organizing center cytoskeleton membraneless organelle intracellular membraneless organelle microtubule cytoskeleton nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen mitochondrial matrix
B	LYR motif-containing protein 4	identical protein binding protein binding binding protein homodimerization activity protein dimerization activity	cellular component biogenesis cellular component organization metallo-sulfur cluster assembly cellular component assembly iron-sulfur cluster assembly cellular process cellular component organization or biogenesis [2Fe-2S] cluster assembly [4Fe-4S] cluster assembly	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle protein-containing complex cytosol iron-sulfur cluster assembly complex mitochondrial protein-containing complex catalytic complex sulfurtransferase complex transferase complex L-cysteine desulfurase complex mitochondrial [2Fe-2S] assembly complex nucleus membrane-enclosed lumen intracellular organelle lumen nuclear body nucleoplasm organelle lumen nuclear lumen mitochondrial matrix
C	Acyl carrier protein	phosphopantetheine-dependent carrier activity prosthetic group binding binding acyl carrier activity molecular carrier activity ACP phosphopantetheine attachment site binding lipid binding vitamin binding amide binding modified amino acid binding phosphopantetheine binding small molecule binding acyl binding	response to stimulus response to chemical response to xenobiotic stimulus fatty acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process oxoacid metabolic process carboxylic acid metabolic process lipid biosynthetic process primary metabolic process organic acid biosynthetic process organic acid metabolic process fatty acid biosynthetic process carboxylic acid biosynthetic process response to stimulus response to chemical response to xenobiotic stimulus fatty acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process oxoacid metabolic process carboxylic acid metabolic process lipid biosynthetic process primary metabolic process organic acid biosynthetic process organic acid metabolic process fatty acid biosynthetic process carboxylic acid biosynthetic process biosynthetic process small molecule metabolic process metabolic process cellular process monocarboxylic acid metabolic process lipid metabolic process glycolipid metabolic process lipid A biosynthetic process carbohydrate derivative metabolic process phospholipid metabolic process phosphate-containing compound metabolic process lipooligosaccharide biosynthetic process phosphorus metabolic process carbohydrate derivative biosynthetic process membrane lipid metabolic process lipooligosaccharide metabolic process liposaccharide metabolic process glycolipid biosynthetic process phospholipid biosynthetic process lipid A metabolic process organophosphate metabolic process organophosphate biosynthetic process membrane lipid biosynthetic process	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
D	IPR011339	Iron-sulfur cluster assembly scaffold protein IscU	Family
D	IPR002871	NIF system FeS cluster assembly, NifU, N-terminal	Domain
A	IPR020578	Aminotransferase class-V, pyridoxal-phosphate binding site	Binding Site
A	IPR000192	Aminotransferase class V domain	Domain
A	IPR010240	Cysteine desulfurase IscS	Family
A	IPR016454	Cysteine desulfurase	Family
A	IPR015421	Pyridoxal phosphate-dependent transferase, major domain	Homologous Superfamily
A	IPR015422	Pyridoxal phosphate-dependent transferase, small domain	Homologous Superfamily
A	IPR015424	Pyridoxal phosphate-dependent transferase	Homologous Superfamily
B	IPR051522	Iron-sulfur cluster assembly LYR protein	Family
B	IPR008011	Complex 1 LYR protein domain	Domain
B	IPR045297	LYRM4, LYR domain	Domain
C	IPR006162	Phosphopantetheine attachment site	PTM
C	IPR009081	Phosphopantetheine binding ACP domain	Domain
C	IPR036736	ACP-like superfamily	Homologous Superfamily
C	IPR003231	Acyl carrier protein	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
D	Pharos: Q9H1K1	hereditary myopathy with lactic acidosis due to ISCU deficiency arthrogryposis Friedreich ataxia Mitochondrial Diseases astrocytic tumor ovarian cancer large cell medulloblastoma rhabdomyolysis
A	Pharos: Q9Y697	Friedreich ataxia Mitochondrial Diseases skin carcinoma large cell medulloblastoma osteosarcoma medulloblastoma ovarian cancer
B	Pharos: Q9HD34	combined oxidative phosphorylation deficiency 19 breast cancer Friedreich ataxia Mitochondrial Diseases pancreatic intraductal papillary-mucinous neoplasm squamous cell carcinoma combined oxidative phosphorylation deficiency lung cancer osteosarcoma schizophrenia medulloblastoma ovarian cancer skin basal cell carcinoma

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.