Annotations: 4FXF

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
D [auth B]	PK_2nd	e4fxfB2	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PK beta-barrel domain-like	F: PK_2nd	ECOD (1.6)
D [auth B]	PK_1st	e4fxfB3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PK_1st	ECOD (1.6)
D [auth B]	PK_C	e4fxfB1	A: a/b three-layered sandwiches	X: PK C-terminal domain-like (From Topology)	H: PK C-terminal domain-like (From Topology)	T: PK C-terminal domain-like	F: PK_C	ECOD (1.6)
A	PK_2nd	e4fxfA3	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PK beta-barrel domain-like	F: PK_2nd	ECOD (1.6)
A	PK_1st	e4fxfA1	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PK_1st	ECOD (1.6)
A	PK_C	e4fxfA2	A: a/b three-layered sandwiches	X: PK C-terminal domain-like (From Topology)	H: PK C-terminal domain-like (From Topology)	T: PK C-terminal domain-like	F: PK_C	ECOD (1.6)
B [auth D]	PK_2nd	e4fxfD2	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PK beta-barrel domain-like	F: PK_2nd	ECOD (1.6)
B [auth D]	PK_1st	e4fxfD1	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PK_1st	ECOD (1.6)
B [auth D]	PK_C	e4fxfD3	A: a/b three-layered sandwiches	X: PK C-terminal domain-like (From Topology)	H: PK C-terminal domain-like (From Topology)	T: PK C-terminal domain-like	F: PK_C	ECOD (1.6)
C	PK_2nd	e4fxfC2	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: PK beta-barrel domain-like	F: PK_2nd	ECOD (1.6)
C	PK_1st	e4fxfC1	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PK_1st	ECOD (1.6)
C	PK_C	e4fxfC3	A: a/b three-layered sandwiches	X: PK C-terminal domain-like (From Topology)	H: PK C-terminal domain-like (From Topology)	T: PK C-terminal domain-like	F: PK_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D [auth B]	3.40.1380.20	Alpha Beta	3-Layer(aba) Sandwich	Pyruvate Kinase	Chain: A, domain 1	CATH (4.3.0)
D [auth B]	3.20.20.60	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Phosphoenolpyruvate-binding domains	CATH (4.3.0)
D [auth B]	2.40.33.10	Mainly Beta	Beta Barrel	M1 Pyruvate Kinase	Domain 3	CATH (4.3.0)
A	3.40.1380.20	Alpha Beta	3-Layer(aba) Sandwich	Pyruvate Kinase	Chain: A, domain 1	CATH (4.3.0)
A	3.20.20.60	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Phosphoenolpyruvate-binding domains	CATH (4.3.0)
A	2.40.33.10	Mainly Beta	Beta Barrel	M1 Pyruvate Kinase	Domain 3	CATH (4.3.0)
B [auth D]	3.40.1380.20	Alpha Beta	3-Layer(aba) Sandwich	Pyruvate Kinase	Chain: A, domain 1	CATH (4.3.0)
B [auth D]	3.20.20.60	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Phosphoenolpyruvate-binding domains	CATH (4.3.0)
B [auth D]	2.40.33.10	Mainly Beta	Beta Barrel	M1 Pyruvate Kinase	Domain 3	CATH (4.3.0)
C	3.40.1380.20	Alpha Beta	3-Layer(aba) Sandwich	Pyruvate Kinase	Chain: A, domain 1	CATH (4.3.0)
C	3.20.20.60	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Phosphoenolpyruvate-binding domains	CATH (4.3.0)
C	2.40.33.10	Mainly Beta	Beta Barrel	M1 Pyruvate Kinase	Domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B [auth D], C, D [auth B]	PF02887	Pyruvate kinase, alpha/beta domain (PK_C)	Pyruvate kinase, alpha/beta domain	Pyruvate kinase catalyses the final step in glycolysis, the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP [1,2]. The structure of several pyruvate kinases from various organisms have been determined [2, ...	Pyruvate kinase catalyses the final step in glycolysis, the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP [1,2]. The structure of several pyruvate kinases from various organisms have been determined [2, 3,4]. The protein comprises three-four domains: a small N-terminal helical domain (absent in bacterial PK), a beta/alpha barrel domain, a beta-barrel domain (inserted within the beta/alpha-barrel domain), and a 3-layer alpha/beta/alpha sandwich domain (represented in this entry). This domain is at the C-terminal of pyruvate kinases and contains the FBP (fructose 1,6-bisphosphate) binding site [2,4,5].	Domain
A, B [auth D], C, D [auth B]	PF00224	Pyruvate kinase, barrel domain (PK)	Pyruvate kinase, barrel domain	This is the barrel domain of pyruvate kinases. This domain represents the beta/alpha barrel and the small beta-barrel domain inserted within it. The active site is found in a cleft between the two domains [1,2,3,4].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B [auth D], C, D [auth B]	Pyruvate kinase isozymes M1/M2	cation binding ion binding binding potassium ion binding alkali metal ion binding metal ion binding small molecule binding transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding MHC protein complex binding cation binding ion binding binding potassium ion binding alkali metal ion binding metal ion binding small molecule binding transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding MHC protein complex binding MHC class II protein complex binding RNA binding organic cyclic compound binding nucleic acid binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups magnesium ion binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding mRNA binding identical protein binding protein binding protein homodimerization activity protein dimerization activity cell adhesion molecule binding cadherin binding protein serine/threonine kinase activity histone H3 kinase activity histone modifying activity histone H3T11 kinase activity histone kinase activity pyruvate kinase activity	cellular process cell death programmed cell death ribonucleotide catabolic process pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process organic acid metabolic process nucleobase-containing compound metabolic process glycolytic process phosphate-containing compound metabolic process cellular process cell death programmed cell death ribonucleotide catabolic process pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process organic acid metabolic process nucleobase-containing compound metabolic process glycolytic process phosphate-containing compound metabolic process pyridine-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process phosphorus metabolic process pyridine nucleotide metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process cellular metabolic process purine nucleoside diphosphate metabolic process primary metabolic process purine-containing compound catabolic process nucleotide metabolic process nucleobase-containing compound catabolic process nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process metabolic process nucleoside triphosphate metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process catabolic process ATP metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process nucleotide catabolic process ribonucleoside triphosphate metabolic process purine nucleoside triphosphate metabolic process purine nucleotide catabolic process carbohydrate metabolic process carbohydrate derivative catabolic process ADP catabolic process carboxylic acid metabolic process generation of precursor metabolites and energy purine-containing compound metabolic process ADP metabolic process organophosphate metabolic process purine ribonucleoside diphosphate metabolic process purine ribonucleoside diphosphate catabolic process regulation of cellular process cellular biosynthetic process positive regulation of protein metabolic process positive regulation of biological process positive regulation of translation positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process post-transcriptional regulation of gene expression positive regulation of metabolic process positive regulation of cytoplasmic translation positive regulation of biosynthetic process positive regulation of macromolecule metabolic process protein metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process regulation of protein metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression translation macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of translation cytoplasmic translation regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of cytoplasmic translation regulation of metabolic process positive regulation of cellular biosynthetic process multicellular organismal process regulation of sprouting angiogenesis regulation of developmental process angiogenesis regulation of vasculature development positive regulation of developmental process multicellular organism development tube morphogenesis anatomical structure development positive regulation of sprouting angiogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development system development developmental process regulation of multicellular organismal development blood vessel morphogenesis tube development positive regulation of angiogenesis sprouting angiogenesis vasculature development circulatory system development anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis positive regulation of multicellular organismal process cellular response to nitrogen compound cellular response to stimulus response to stimulus response to endogenous stimulus response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical response to insulin cellular response to insulin stimulus cellular response to hormone stimulus NADH regeneration glucose catabolic process to pyruvate hexose catabolic process hexose metabolic process NADH metabolic process glucose catabolic process monosaccharide catabolic process small molecule catabolic process monosaccharide metabolic process canonical glycolysis NAD metabolic process glycolytic process through glucose-6-phosphate NAD catabolic process glycolytic process through fructose-6-phosphate glucose metabolic process positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle cell projection cilium plasma membrane bounded cell projection vesicle extracellular exosome extracellular vesicle membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle cell projection cilium plasma membrane bounded cell projection vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cytosol membrane-enclosed lumen intracellular vesicle ficolin-1-rich granule endomembrane system intracellular organelle lumen organelle lumen cytoplasmic vesicle ficolin-1-rich granule lumen secretory granule secretory vesicle rough endoplasmic reticulum endoplasmic reticulum vesicle lumen cytoplasmic vesicle lumen secretory granule lumen nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B [auth D], C, D [auth B]	IPR011037	Pyruvate kinase-like, insert domain superfamily	Homologous Superfamily
A, B [auth D], C, D [auth B]	IPR015806	Pyruvate kinase, insert domain superfamily	Homologous Superfamily
A, B [auth D], C, D [auth B]	IPR036918	Pyruvate kinase, C-terminal domain superfamily	Homologous Superfamily
A, B [auth D], C, D [auth B]	IPR040442	Pyruvate kinase-like domain superfamily	Homologous Superfamily
A, B [auth D], C, D [auth B]	IPR015793	Pyruvate kinase, barrel	Domain
A, B [auth D], C, D [auth B]	IPR015795	Pyruvate kinase, C-terminal	Domain
A, B [auth D], C, D [auth B]	IPR015813	Pyruvate/Phosphoenolpyruvate kinase-like domain superfamily	Homologous Superfamily
A, B [auth D], C, D [auth B]	IPR001697	Pyruvate kinase	Family
A, B [auth D], C, D [auth B]	IPR018209	Pyruvate kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B [auth D], C, D [auth B]	Pharos: P14618	Neoplasm Invasiveness osteoporosis sarcomatoid carcinoma carcinoma malignant ependymoma mammary neoplasms, animal adrenal cortex adenoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma psoriasis breast carcinoma glioblastoma invasive ductal breast carcinoma lung adenocarcinoma malignant pancreatic neoplasm Neoplasm Invasiveness osteoporosis sarcomatoid carcinoma carcinoma malignant ependymoma mammary neoplasms, animal adrenal cortex adenoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma psoriasis breast carcinoma glioblastoma invasive ductal breast carcinoma lung adenocarcinoma malignant pancreatic neoplasm non-small cell lung carcinoma adrenal cortex carcinoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm astrocytic tumor cancer ulcerative colitis dermatomyositis hepatocellular carcinoma large cell medulloblastoma lung cancer medulloblastoma oligodendroglioma pancreatic ductal adenocarcinoma atypical teratoid rhabdoid tumor rheumatoid arthritis undifferentiated carcinoma ductal breast carcinoma in situ interstitial lung disease

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.