6HXH

Structure of the human ATP citrate lyase holoenzyme in complex with citrate, coenzyme A and Mg.ADP

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	CoA-binding Rossmann-fold domain	8053670	3000049	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053666	3000003	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Succinyl-CoA synthetase domain-like	8053668	3000003	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Glutathione synthetase ATP-binding domain-like	8053676	3000094	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)
A	Citrate_synt	e6hxhA4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
A	ATP-grasp_2	e6hxhA1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
A	CoA_binding	e6hxhA5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
A	Succ_CoA_lig	e6hxhA2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
A	Citrate_bind	e6hxhA3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
B	Citrate_synt	e6hxhB4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
B	ATP-grasp_2	e6hxhB1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
B	CoA_binding	e6hxhB5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
B	Succ_CoA_lig	e6hxhB2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
B	Citrate_bind	e6hxhB3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
C	Citrate_synt	e6hxhC4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
C	ATP-grasp_2	e6hxhC1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
C	CoA_binding	e6hxhC5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
C	Succ_CoA_lig	e6hxhC2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
C	Citrate_bind	e6hxhC3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
D	Citrate_synt	e6hxhD4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
D	ATP-grasp_2	e6hxhD1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
D	CoA_binding	e6hxhD5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
D	Succ_CoA_lig	e6hxhD2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
D	Citrate_bind	e6hxhD3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
E	Citrate_synt	e6hxhE4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
E	ATP-grasp_2	e6hxhE1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
E	CoA_binding	e6hxhE5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
E	Succ_CoA_lig	e6hxhE2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
E	Citrate_bind	e6hxhE3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
F	Citrate_synt	e6hxhF4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
F	ATP-grasp_2	e6hxhF1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
F	CoA_binding	e6hxhF5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
F	Succ_CoA_lig	e6hxhF2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
F	Citrate_bind	e6hxhF3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
G	Citrate_synt	e6hxhG4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
G	ATP-grasp_2	e6hxhG1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
G	CoA_binding	e6hxhG5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
G	Succ_CoA_lig	e6hxhG2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
G	Citrate_bind	e6hxhG3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)
H	Citrate_synt	e6hxhH4	A: alpha complex topology	X: Citrate synthase-like	H: Citrate synthase (From Topology)	T: Citrate synthase	F: Citrate_synt	ECOD (1.6)
H	ATP-grasp_2	e6hxhH1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: ATP-grasp	F: ATP-grasp_2	ECOD (1.6)
H	CoA_binding	e6hxhH5	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: CoA_binding	ECOD (1.6)
H	Succ_CoA_lig	e6hxhH2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Succ_CoA_lig	ECOD (1.6)
H	Citrate_bind	e6hxhH3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Succinyl-CoA synthetase domains (From Topology)	T: Succinyl-CoA synthetase domains	F: Citrate_bind	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E A, B, C, D, E, F, G, H	PF00549	CoA-ligase (Ligase_CoA)	CoA-ligase	This family includes the CoA ligases Succinyl-CoA synthetase alpha and beta chains, malate CoA ligase and ATP-citrate lyase. Some members of the family utilise ATP others use GTP.	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	PF02629	CoA binding domain (CoA_binding)	CoA binding domain	This domain has a Rossmann fold and is found in a number of proteins including succinyl CoA synthetases, malate and ATP-citrate ligases.	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	PF16114	ATP citrate lyase citrate-binding (Citrate_bind)	ATP citrate lyase citrate-binding	This is the citrate-binding domain of ATP citrate lyase. This domain has a Rossmann fold [1].	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	PF00285	Citrate synthase, C-terminal domain (Citrate_synt)	Citrate synthase, C-terminal domain	This is the long, C-terminal part of the enzyme.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E A, B, C, D, E, F, G, H	ATP-citrate synthase,Human ATP citrate lyase	binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding ATP citrate synthase activity acyltransferase activity acyltransferase activity, acyl groups converted into alkyl on transfer transferase activity catalytic activity cation binding metal ion binding	biosynthetic process lipid biosynthetic process primary metabolic process metabolic process lipid metabolic process tricarboxylic acid metabolic process oxoacid metabolic process cellular metabolic process carboxylic acid metabolic process small molecule metabolic process cellular process organic acid metabolic process citrate metabolic process thioester biosynthetic process biosynthetic process lipid biosynthetic process primary metabolic process metabolic process lipid metabolic process tricarboxylic acid metabolic process oxoacid metabolic process cellular metabolic process carboxylic acid metabolic process small molecule metabolic process cellular process organic acid metabolic process citrate metabolic process thioester biosynthetic process cellular biosynthetic process acetyl-CoA metabolic process nucleobase-containing compound metabolic process acyl-CoA metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process phosphate-containing compound metabolic process sulfur compound metabolic process amide metabolic process thioester metabolic process phosphorus metabolic process nucleoside phosphate metabolic process amide biosynthetic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process sulfur compound biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process secondary alcohol biosynthetic process small molecule biosynthetic process cholesterol biosynthetic process organic hydroxy compound metabolic process sterol metabolic process steroid metabolic process cholesterol metabolic process alcohol metabolic process secondary alcohol metabolic process sterol biosynthetic process organic hydroxy compound biosynthetic process alcohol biosynthetic process steroid biosynthetic process fatty acid metabolic process monocarboxylic acid biosynthetic process organic acid biosynthetic process fatty acid biosynthetic process carboxylic acid biosynthetic process cellular lipid metabolic process monocarboxylic acid metabolic process coenzyme A metabolic process dicarboxylic acid metabolic process oxaloacetate metabolic process	membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol membrane cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol lytic vacuole intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen vacuolar lumen endomembrane system intracellular organelle lumen intracellular organelle cytoplasmic vesicle lysosome vesicle lumen azurophil granule vacuole intracellular membrane-bounded organelle secretory granule lumen azurophil granule lumen organelle lumen secretory granule primary lysosome secretory vesicle ficolin-1-rich granule ficolin-1-rich granule lumen nucleus nucleoplasm nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E A, B, C, D, E, F, G, H	IPR032263	ATP-citrate synthase, citrate-binding domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	IPR016102	Succinyl-CoA synthetase-like	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H	IPR017440	ATP-citrate lyase/succinyl-CoA ligase, active site	Active Site
A, B, C, D, E A, B, C, D, E, F, G, H	IPR016143	Citrate synthase-like, small alpha subdomain	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H	IPR017866	Succinyl-CoA synthetase, beta subunit, conserved site	Conserved Site
A, B, C, D, E A, B, C, D, E, F, G, H	IPR003781	CoA-binding	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	IPR036969	Citrate synthase superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H	IPR005811	ATP-citrate synthase/succinyl-CoA ligase, C-terminal domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H	IPR014608	ATP-citrate synthase	Family
A, B, C, D, E A, B, C, D, E, F, G, H	IPR033847	ATP-citrate lyase/succinyl-CoA ligase, conserved site	Conserved Site
A, B, C, D, E A, B, C, D, E, F, G, H	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H	IPR002020	Citrate synthase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D, E A, B, C, D, E, F, G, H	Pharos: P53396	obesity disorder congestive heart failure pilocytic astrocytoma Sjogren syndrome astrocytic tumor Heart Decompensation hepatocellular carcinoma lymphoplasmacytic lymphoma osteosarcoma plasma cell myeloma Emery-Dreifuss muscular dystrophy heart failure juvenile dermatomyositis malignant ependymoma myopathy obesity disorder congestive heart failure pilocytic astrocytoma Sjogren syndrome astrocytic tumor Heart Decompensation hepatocellular carcinoma lymphoplasmacytic lymphoma osteosarcoma plasma cell myeloma Emery-Dreifuss muscular dystrophy heart failure juvenile dermatomyositis malignant ependymoma myopathy ovarian cancer psoriasis breast cancer large cell medulloblastoma lung adenocarcinoma medulloblastoma