Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004743 pyruvate kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred pyruvate kinase activity, the defining molecular function of PKLR and the entire pyruvate kinase family. Reason: This is the core molecular function of the gene product, catalysing PEP + ADP -> pyruvate + ATP (EC 2.7.1.40). It is directly supported by biochemical and structural characterization of human RPK and by the UniProt catalytic-activity annotation, and is consistent across the pyruvate kinase phylogeny. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt Pyruvate kinase that catalyzes the conversion of
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic assignment of cytoplasmic localization; correct but less informative than the specific cytosol term. Reason: PKLR is a soluble glycolytic enzyme active in the cytosol. Cytoplasm is correct but is subsumed by the more informative GO:0005829 cytosol annotation (TAS, Reactome), so it is retained as a non-core, general localization statement.
GO:0006096 glycolytic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred participation in glycolysis; PKLR catalyses the final ATP-generating step of the pathway. Reason: Pyruvate kinase catalyses glycolysis step 5/5 (pyruvate from D-glyceraldehyde 3-phosphate), the committed, essentially irreversible PEP -> pyruvate reaction that generates ATP. This is a core biological process for the gene product. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
GO:0032869 cellular response to insulin stimulus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetically projected involvement in the cellular insulin response, reflecting hormonal regulation of the liver isoform rather than PKLR's own molecular function. Reason: The liver (L) isoform's expression and phosphorylation state are modulated by insulin/glucagon signalling, but this describes upstream regulation of the enzyme, not a process PKLR itself carries out. The phylogenetic support is thin (only two source annotations, PANTHER + rat RGD) and the term over-states PKLR's role in insulin signalling; it is retained but flagged as an over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: RGD:3336 · Pklr (rat) SUPPORTS SOURCE BUT NOT TARGET Rat ortholog regulatory/physiological context; captures hormonal regulation of the hepatic enzyme, not a molecular process PKLR itself performs. PANTHER:PTN000212861 · pyruvate kinase family node SUPPORTS SOURCE BUT NOT TARGET Family-node projection of a regulatory biological process, thinly supported (two source annotations only).
GO:0000287 magnesium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based assignment of magnesium ion binding, the catalytic divalent metal cofactor of pyruvate kinase. Reason: Pyruvate kinase requires a divalent metal cofactor (Mg2+, or Mn2+ in vitro) for catalysis; UniProt lists Mg(2+) and Mn(2+) as cofactors and the human RPK crystal structure resolves the catalytic divalent-metal site. The InterPro mapping is structurally supported. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
GO:0004743 pyruvate kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated multi-method assignment of pyruvate kinase activity (EC 2.7.1.40, RHEA:18157), the core catalytic function. Reason: Redundant electronic support (mapping via EC 2.7.1.40, RHEA:18157 and PK InterPro domains) for the experimentally established pyruvate kinase activity; correct and consistent with the EXP/TAS/IBA evidence. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt EC=2.7.1.40 {ECO:0000269\|PubMed:11960989}
GO:0006096 glycolytic process	IEA GO_REF:0000120	ACCEPT	Summary: Automated multi-method assignment (via UniPathway glycolysis) of participation in the glycolytic process. Reason: Redundant electronic support for PKLR's role in glycolysis, consistent with the UniProt pathway annotation and the IBA glycolytic process annotation. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
GO:0030955 potassium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based assignment of potassium ion binding, the required monovalent cation cofactor of pyruvate kinase. Reason: Pyruvate kinase activity requires K+; the human RPK structure resolves the K+ site (binding residues 118, 120, 156, 157) and UniProt lists K(+) as a cofactor. The InterPro mapping is structurally supported. Supporting Evidence: file:human/PKLR/PKLR-uniprot.txt Name=K(+); Xref=ChEBI:CHEBI:29103;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Single high-throughput yeast two-hybrid interaction (with CPNE7, UniProt Q9UBL6-2) from the HuRI reference interactome; uninformative bare protein-binding term. Reason: GO:0005515 protein binding conveys no specific molecular function and derives from a single systematic Y2H screen (HuRI) reporting a PKLR-CPNE7 interaction with no functional characterization or independent orthogonal validation for PKLR. Per curation guidance this bare protein-binding IPI is retained but flagged as an over-annotation rather than treated as a core function. Supporting Evidence: PMID:32296183 With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies.
GO:0001666 response to hypoxia	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to hypoxia projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: This is an orthology-transferred physiological/regulatory context (glycolytic flux is modulated under hypoxia), not PKLR's own molecular function. Biologically plausible for a glycolytic enzyme but peripheral to the core catalytic role, so retained as non-core.
GO:0007584 response to nutrient	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to nutrient projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: Reflects nutritional/dietary regulation of the hepatic pyruvate kinase isoform's expression rather than PKLR's molecular function. Retained as a non-core, orthology-inferred regulatory context.
GO:0009749 response to glucose	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to glucose projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: Hepatic pyruvate kinase (L isoform) transcription is induced by dietary glucose/carbohydrate; this is a regulatory context transferred from the rat ortholog, not PKLR's molecular activity. Retained as non-core.
GO:0010038 response to metal ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to metal ion projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: Pyruvate kinase depends on Mg2+/Mn2+ and K+ as catalytic cofactors, so metal-ion sensitivity is biologically plausible, but this orthology-transferred biological-process term overlaps with the more precise metal-ion-binding molecular-function annotations and is peripheral to the core function. Retained as non-core.
GO:0032869 cellular response to insulin stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Cellular insulin response projected electronically from the rat ortholog (P12928); reflects hormonal regulation of the liver isoform, not PKLR's molecular function. Reason: Duplicates the IBA cellular-response-to-insulin annotation via orthology transfer. It captures upstream insulin/glucagon regulation of hepatic pyruvate kinase expression and phosphorylation rather than a process PKLR itself performs; retained but flagged as an over-annotation.
GO:0033198 response to ATP	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to ATP projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: ATP is both a product of the pyruvate kinase reaction and a classic allosteric inhibitor of the enzyme, so ATP-sensitivity is biologically real, but this orthology-transferred biological-process term is peripheral to the core catalytic function. Retained as non-core.
GO:0042866 pyruvate biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Pyruvate biosynthesis projected electronically from the rat ortholog (P12928); an alternative process framing of the pyruvate kinase reaction, whose product is pyruvate. Reason: Pyruvate is the direct product of the pyruvate kinase reaction, so this is a correct but redundant restatement of the glycolytic function. It duplicates the Reactome TAS pyruvate-biosynthetic-process annotation and is subsumed by the glycolytic-process core annotation; retained as non-core.
GO:0048029 monosaccharide binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Monosaccharide binding projected electronically from the rat ortholog (P12928); likely a misleading generalization of fructose 1,6-bisphosphate allosteric binding. Reason: PKLR is allosterically activated by fructose 1,6-bisphosphate, a bisphosphorylated hexose, via a dedicated allosteric site. Generalizing this to broad monosaccharide binding is misleading (FBP is a phosphorylated sugar bisphosphate, not a free monosaccharide) and adds no informative molecular function. Retained but flagged as an over-annotation.
GO:0051591 response to cAMP	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to cAMP projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: Glucagon raises hepatic cAMP, activating PKA, which phosphorylates and inhibits the liver pyruvate kinase isoform; cAMP-responsiveness is therefore biologically plausible but represents upstream regulation rather than PKLR's molecular function. Retained as non-core.
GO:0071872 cellular response to epinephrine stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cellular epinephrine response projected electronically from the rat ortholog (P12928) via Ensembl Compara orthology. Reason: Epinephrine, like glucagon, elevates cAMP/PKA signalling that regulates hepatic pyruvate kinase activity by phosphorylation; this is an orthology-transferred regulatory context peripheral to PKLR's core catalytic function. Retained as non-core.
GO:0042866 pyruvate biosynthetic process	TAS Reactome:R-HSA-70268	KEEP AS NON CORE	Summary: Reactome-asserted involvement in pyruvate biosynthesis, reflecting that pyruvate is the product of the pyruvate kinase reaction. Reason: Correct product-oriented framing of the same PEP -> pyruvate reaction that is captured more informatively by the glycolytic-process and pyruvate-kinase-activity core annotations. Retained as non-core to avoid redundancy with the core function.
GO:0061621 canonical glycolysis	TAS Reactome:R-HSA-70171	ACCEPT	Summary: Reactome-asserted participation in canonical glycolysis (Embden-Meyerhof-Parnas pathway), the final ATP-generating step of which PKLR catalyses. Reason: Canonical glycolysis is a precise subtype of glycolytic process describing the classic glucose-to-pyruvate EMP pathway, of which pyruvate kinase catalyses the terminal committed step. This accurately captures PKLR's biological process role.
GO:0004743 pyruvate kinase activity	EXP PMID:11960989 Structure and function of human erythrocyte pyruvate kinase....	ACCEPT	Summary: Experimentally demonstrated pyruvate kinase activity of human erythrocyte RPK, characterized structurally and kinetically together with disease mutants. Reason: This study solved the crystal structure of human RPK in complex with fructose 1,6-bisphosphate and a substrate analogue and functionally characterized wild-type and mutant enzymes, directly establishing the pyruvate kinase catalytic activity that is the core molecular function of PKLR. Supporting Evidence: PMID:11960989 we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue
GO:0004743 pyruvate kinase activity	EXP PMID:15996096 Structural basis for tumor pyruvate kinase M2 allosteric reg...	ACCEPT	Summary: Pyruvate kinase activity supported by a structural/mechanistic study; the cited paper characterizes the human M2 isozyme (PKM gene), applied to PKLR by isozyme analogy via Reactome. Reason: The pyruvate kinase catalytic activity assignment is correct for PKLR and independently established by human RPK biochemistry (PMID:11960989). This particular Reactome-sourced EXP citation is the PKM2 crystallography paper (a paralog); the catalytic mechanism, cofactor (Mg2+/K+) and FBP allostery are conserved across the L/R/M1/M2 isozymes, so it does not conflict with the annotation. Per curation policy the experimental annotation is retained rather than removed; reference relevance is flagged as MEDIUM (paralog-derived). Supporting Evidence: PMID:15996096 The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of PKLR in urinary exosomes; a common MS finding for abundant cytosolic enzymes rather than a functional location. Reason: Detection in an exosome/extracellular-vesicle proteome is a frequent incidental finding for highly abundant soluble glycolytic enzymes and does not reflect where PKLR performs its catalytic function (the cytosol). Retained as a non-core localization observation. Supporting Evidence: PMID:19056867 we used LC-MS/MS to profile the proteome of human urinary exosomes
GO:0005829 cytosol	TAS Reactome:R-HSA-71670	ACCEPT	Summary: Reactome-asserted cytosolic localization, the compartment where PKLR catalyses the glycolytic pyruvate kinase reaction. Reason: PKLR is a soluble cytosolic enzyme; glycolysis occurs in the cytosol and the pyruvate kinase step is cytosolic. This is the informative subcellular location and represents the core cellular component for the gene product.
GO:0005829 cytosol	TAS Reactome:R-HSA-9727857	ACCEPT	Summary: Reactome-asserted cytosolic localization (from a SARS-CoV-1 host-interaction model), consistent with PKLR being a soluble cytosolic enzyme. Reason: Duplicate cytosol localization from a different Reactome reaction; correct and consistent with the primary glycolysis-based cytosol annotation. Cytosol is the core cellular component for PKLR.
GO:0004743 pyruvate kinase activity	TAS PMID:3126495 Human liver type pyruvate kinase: complete amino acid sequen...	ACCEPT	Summary: Author-stated pyruvate kinase activity from the study that cloned and expressed human liver (L)-type PK, detecting enzymatic activity in transfected cells. Reason: This paper determined the full-length human L-type PK cDNA and expressed it in COS cells, where L-type PK activity was detected, corroborating the core pyruvate kinase molecular function of PKLR. Supporting Evidence: PMID:3126495 Human L-type PK activity was detected in the extract of COS cells by the classical PK electrophoresis method.
GO:0004743 pyruvate kinase activity	NAS PMID:1445295 Structural analysis of human pyruvate kinase L-gene and iden...	ACCEPT	Summary: Non-traceable author statement of pyruvate kinase identity from a study of the human PK L-gene structure and its erythroid promoter. Reason: This paper characterizes the human pyruvate kinase L-gene (12 exons, R- and L-type transcripts from alternative first exons) and its promoter; the pyruvate kinase activity assignment is correct for the gene, though the evidence here is genomic/promoter rather than a direct activity assay. Consistent with the stronger EXP/TAS evidence, so accepted. Supporting Evidence: PMID:1445295 The human pyruvate kinase (PK) L-gene is organized in 12 exons over 9.5

Core Functions

Catalyses the final, committed, essentially irreversible ATP-generating step of glycolysis, transferring phosphate from phosphoenolpyruvate to ADP to form pyruvate and ATP (EC 2.7.1.40), requiring Mg2+/Mn2+ and K+ as cofactors and allosterically activated by fructose 1,6-bisphosphate.

Molecular Function:

pyruvate kinase activity

Directly Involved In:

glycolytic process

Cellular Locations:

cytosol

Supporting Evidence:

PMID:11960989
we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue
file:human/PKLR/PKLR-uniprot.txt
Pyruvate kinase that catalyzes the conversion of

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

file:human/PKLR/PKLR-uniprot.txt

UniProtKB P30613 (KPYR_HUMAN) Pyruvate kinase PKLR

PMID:11960989

Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia.

PMID:1445295

Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells.

PMID:15996096

Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:3126495

Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells.

PMID:32296183

A reference map of the human binary protein interactome.

Reactome:R-HSA-70171

Glycolysis

Reactome:R-HSA-70268

Pyruvate metabolism

Reactome:R-HSA-71670

Pyruvate kinase dephosphorylates PEP to PYR

Reactome:R-HSA-9727857

SARS-CoV-1 SUMO1-K62-p-S177-N dimer binds to PKL

📚 Additional Documentation

Notes

(PKLR-notes.md)

PKLR (human) review notes

UniProtKB: P30613 (KPYR_HUMAN). HGNC:9020. Gene: PKLR (synonyms PK1, PKL).
No falcon deep-research file (falcon out of credits, HTTP 402). Review grounded in
PKLR-uniprot.txt, PKLR-goa.tsv, and cached publications/PMID_*.md.

Core biology (from UniProt + literature)

PKLR encodes the L (liver) and R (red-blood-cell) isozymes of pyruvate kinase,
produced by alternative promoters/splicing of a single gene (exon 1 = R mRNA, exon 2 =
L mRNA) PMID:1445295. The separate PKM gene encodes the M1/M2 isozymes.
UniProt MISCELLANEOUS: "There are 4 isozymes of pyruvate kinase in mammals: L, R, M1
and M2. L type is major isozyme in the liver, R is found in red cells, M1 is the main
form in muscle, heart and brain, and M2 is found in early fetal tissues."
Reaction (EC 2.7.1.40): phosphoenolpyruvate (PEP) + ADP → pyruvate + ATP; the
final, essentially irreversible, second ATP-generating step of glycolysis
(glycolysis step 5/5, pyruvate from D-glyceraldehyde 3-phosphate; UniPathway UPA00109).
UniProt CATALYTIC ACTIVITY: "Reaction=pyruvate + ATP = phosphoenolpyruvate + ADP + H(+)".
FUNCTION: "Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to
pyruvate with the synthesis of ATP, and which plays a key role in glycolysis
(PubMed:11960989)." PMID:11960989
Cofactors: Mg2+ (or Mn2+ in vitro) and K+ required. UniProt COFACTOR lists Mg(2+),
Mn(2+), K(+). Crystal structure (2VGB/2VGF, 2.73 A) solved with K+ and Mn2+ ions;
K+ binding residues 118/120/156/157, Mn2+ (catalytic divalent) at 315/339 PMID:11960989.
GO magnesium ion binding GO:0000287 and potassium ion binding GO:0030955 (IEA/InterPro)
are structurally supported.
Allosteric regulation: activated by fructose 1,6-bisphosphate (feed-forward);
FBP-binding residues 475-480, 525, 532, 559-564 PMID:11960989. UniProt ACTIVITY
REGULATION: "Allosterically activated by fructose 1,6-bisphosphate." Homotetramer
(UniProt SUBUNIT). Liver isoform additionally inhibited by phosphorylation
(glucagon/PKA) and by ATP/alanine (classic biochemistry).
Side reaction / metabolite repair: also produces the side product 2-phospholactate
((S)-lactate + ATP = (2S)-2-phospholactate + ADP + H+), removed by PGP PMID:27294321.
(PMID:27294321 not cached; UniProt-only, so not used as a supporting_text.)
Structure: 574 aa homotetramer; classic PK fold (Pfam PK PF00224 + PK_C PF02887;
InterPro IPR001697). Many X-ray structures (2VGB, 4IMA, 6NN4, etc.).

Disease

CNSHA2 / pyruvate kinase deficiency (MIM:266200): autosomal recessive; most common
glycolytic-enzyme cause of hereditary nonspherocytic hemolytic anemia. Mature
erythrocytes lack mitochondria and depend entirely on glycolytic ATP, so RPK loss is
hemolytic. Dozens of CNSHA2 missense variants in UniProt. PMID:11960989 abstract:
"Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6-phosphate
dehydrogenase deficiency, the most common cause of the nonspherocytic hemolytic anemia."
PKHYP (MIM:102900): autosomal dominant increase of RBC ATP (variant K37Q/G37E)
PMID:9090535.
Drug: mitapivat (PK activator) approved for PK deficiency (UniProt DrugBank DB16236).

Annotation review decisions (summary)

Core, accepted:
- GO:0004743 pyruvate kinase activity — multiple EXP/TAS/IBA/IEA; core MF. ACCEPT all.
- GO:0006096 glycolytic process — IBA + IEA; core BP. ACCEPT.
- GO:0005829 cytosol — TAS Reactome; correct cellular location. ACCEPT.
- GO:0000287 magnesium ion binding (IEA/InterPro) — structurally supported cofactor. ACCEPT.
- GO:0030955 potassium ion binding (IEA/InterPro) — structurally supported cofactor. ACCEPT.
- GO:0005737 cytoplasm (IBA) — correct but general; cytosol is the informative term. KEEP_AS_NON_CORE.

Accepted non-core / kept:
- GO:0042866 pyruvate biosynthetic process (TAS Reactome, IEA) — pyruvate is the product;
acceptable framing of the same reaction. KEEP_AS_NON_CORE.
- GO:0061621 canonical glycolysis (TAS Reactome) — more specific glycolysis term; ACCEPT.
- GO:0070062 extracellular exosome (HDA) — high-throughput proteomics localization; a
common HDA finding for abundant cytosolic enzymes, not a functional site. KEEP_AS_NON_CORE.

Over-annotations (kept, flagged):
- GO:0005515 protein binding (IPI, HuRI Y2H hit vs CPNE7, Q9UBL6-2) — bare protein binding,
uninformative, single large-scale Y2H. MARK_AS_OVER_ANNOTATED (policy: not REMOVE).
- GO:0032869 cellular response to insulin stimulus (IBA + IEA) — regulatory/physiological
context transferred from rat ortholog; not PKLR's molecular function. MARK_AS_OVER_ANNOTATED.
- GO:0048029 monosaccharide binding (IEA/Ensembl from rat) — over-broad; FBP is a
bisphosphorylated sugar allosteric activator, but "monosaccharide binding" is a
misleading generalization of that. MARK_AS_OVER_ANNOTATED.

IEA physiological-response transfers from the rat ortholog (P12928) via GO_REF:0000107
(Ensembl Compara orthology projection) — these describe regulation of the liver enzyme's
expression/activity by hormones/nutrients, not PKLR's own molecular activity. Keep as
non-core where biologically plausible:
- GO:0001666 response to hypoxia — KEEP_AS_NON_CORE
- GO:0007584 response to nutrient — KEEP_AS_NON_CORE
- GO:0009749 response to glucose — KEEP_AS_NON_CORE
- GO:0010038 response to metal ion — KEEP_AS_NON_CORE (Mg/K/Mn are cofactors; plausible)
- GO:0033198 response to ATP — KEEP_AS_NON_CORE (ATP is substrate/product + inhibitor)
- GO:0051591 response to cAMP — KEEP_AS_NON_CORE (glucagon/PKA regulation of L isoform)
- GO:0071872 cellular response to epinephrine stimulus — KEEP_AS_NON_CORE

Reference notes

PMID:15996096 is a structure paper on PKM2 (the PKM gene isozyme), used by Reactome
to support GO:0004743 for PKLR by family analogy. Per curation policy, EXP annotation is
not removed on abstract-only grounds; the M2/R isozymes share the catalytic mechanism.
ACCEPT the pyruvate kinase activity annotation; flag the reference relevance as MEDIUM.
PMID:19056867 (urinary exosome proteomics) supports the HDA extracellular exosome
localization; PKLR is not named in the cached abstract (large proteome list). Kept
non-core; reference is LOW relevance to core function.

📄 View Raw YAML

id: P30613
gene_symbol: PKLR
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: PKLR encodes the liver (L) and red-blood-cell (R) isozymes of pyruvate
  kinase, produced from a single gene by alternative promoters and splicing. It catalyses
  the final, essentially irreversible, second ATP-generating step of glycolysis, transferring
  a phosphate from phosphoenolpyruvate (PEP) to ADP to form pyruvate and ATP (EC 2.7.1.40).
  The enzyme is a cytosolic homotetramer that requires Mg2+ (or Mn2+) and K+, is allosterically
  activated in a feed-forward manner by fructose 1,6-bisphosphate, and (in the liver isoform)
  is inhibited by ATP and alanine and by phosphorylation via the glucagon/PKA axis. The
  separate PKM gene encodes the muscle/M1-M2 isozymes. Because mature erythrocytes lack
  mitochondria and depend entirely on glycolysis for ATP, loss-of-function variants cause
  pyruvate kinase deficiency, the most common glycolytic-enzyme cause of hereditary
  nonspherocytic hemolytic anemia; rare hyperactivating variants raise red-cell ATP.
alternative_products:
- name: R-type (PKR)
  id: P30613-1
- name: L-type (PKL)
  id: P30613-2
  sequence_note: VSP_002883
existing_annotations:
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetically inferred pyruvate kinase activity, the defining molecular
      function of PKLR and the entire pyruvate kinase family.
    action: ACCEPT
    reason: This is the core molecular function of the gene product, catalysing PEP
      + ADP -> pyruvate + ATP (EC 2.7.1.40). It is directly supported by biochemical
      and structural characterization of human RPK and by the UniProt catalytic-activity
      annotation, and is consistent across the pyruvate kinase phylogeny.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: Pyruvate kinase that catalyzes the conversion of
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic assignment of cytoplasmic localization; correct but less
      informative than the specific cytosol term.
    action: KEEP_AS_NON_CORE
    reason: PKLR is a soluble glycolytic enzyme active in the cytosol. Cytoplasm is
      correct but is subsumed by the more informative GO:0005829 cytosol annotation
      (TAS, Reactome), so it is retained as a non-core, general localization statement.
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred participation in glycolysis; PKLR catalyses
      the final ATP-generating step of the pathway.
    action: ACCEPT
    reason: Pyruvate kinase catalyses glycolysis step 5/5 (pyruvate from D-glyceraldehyde
      3-phosphate), the committed, essentially irreversible PEP -> pyruvate reaction
      that generates ATP. This is a core biological process for the gene product.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
        D-'
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically projected involvement in the cellular insulin response,
      reflecting hormonal regulation of the liver isoform rather than PKLR's own molecular
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The liver (L) isoform's expression and phosphorylation state are modulated
      by insulin/glucagon signalling, but this describes upstream regulation of the
      enzyme, not a process PKLR itself carries out. The phylogenetic support is thin
      (only two source annotations, PANTHER + rat RGD) and the term over-states PKLR's
      role in insulin signalling; it is retained but flagged as an over-annotation.
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - ROLE_CONFLATION
      - CONTEXT_OR_TISSUE_MISMATCH
      source_entities:
      - source_id: RGD:3336
        source_label: Pklr (rat)
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: Rat ortholog regulatory/physiological context; captures hormonal
          regulation of the hepatic enzyme, not a molecular process PKLR itself performs.
      - source_id: PANTHER:PTN000212861
        source_label: pyruvate kinase family node
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: Family-node projection of a regulatory biological process, thinly
          supported (two source annotations only).
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of magnesium ion binding, the catalytic divalent
      metal cofactor of pyruvate kinase.
    action: ACCEPT
    reason: Pyruvate kinase requires a divalent metal cofactor (Mg2+, or Mn2+ in vitro)
      for catalysis; UniProt lists Mg(2+) and Mn(2+) as cofactors and the human RPK
      crystal structure resolves the catalytic divalent-metal site. The InterPro mapping
      is structurally supported.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Automated multi-method assignment of pyruvate kinase activity (EC 2.7.1.40,
      RHEA:18157), the core catalytic function.
    action: ACCEPT
    reason: Redundant electronic support (mapping via EC 2.7.1.40, RHEA:18157 and PK
      InterPro domains) for the experimentally established pyruvate kinase activity;
      correct and consistent with the EXP/TAS/IBA evidence.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: EC=2.7.1.40 {ECO:0000269|PubMed:11960989}
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Automated multi-method assignment (via UniPathway glycolysis) of participation
      in the glycolytic process.
    action: ACCEPT
    reason: Redundant electronic support for PKLR's role in glycolysis, consistent
      with the UniProt pathway annotation and the IBA glycolytic process annotation.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
        D-'
- term:
    id: GO:0030955
    label: potassium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of potassium ion binding, the required monovalent
      cation cofactor of pyruvate kinase.
    action: ACCEPT
    reason: Pyruvate kinase activity requires K+; the human RPK structure resolves
      the K+ site (binding residues 118, 120, 156, 157) and UniProt lists K(+) as
      a cofactor. The InterPro mapping is structurally supported.
    supported_by:
    - reference_id: file:human/PKLR/PKLR-uniprot.txt
      supporting_text: Name=K(+); Xref=ChEBI:CHEBI:29103;
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Single high-throughput yeast two-hybrid interaction (with CPNE7, UniProt
      Q9UBL6-2) from the HuRI reference interactome; uninformative bare protein-binding
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: 'GO:0005515 protein binding conveys no specific molecular function and
      derives from a single systematic Y2H screen (HuRI) reporting a PKLR-CPNE7 interaction
      with no functional characterization or independent orthogonal validation for
      PKLR. Per curation guidance this bare protein-binding IPI is retained but flagged
      as an over-annotation rather than treated as a core function.'
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: With approximately 53,000 protein-protein interactions, HuRI
        has approximately four times as many such interactions as there are high-quality
        curated interactions from small-scale studies.
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to hypoxia projected electronically from the rat ortholog (P12928)
      via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: This is an orthology-transferred physiological/regulatory context (glycolytic
      flux is modulated under hypoxia), not PKLR's own molecular function. Biologically
      plausible for a glycolytic enzyme but peripheral to the core catalytic role,
      so retained as non-core.
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to nutrient projected electronically from the rat ortholog (P12928)
      via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: Reflects nutritional/dietary regulation of the hepatic pyruvate kinase
      isoform's expression rather than PKLR's molecular function. Retained as a non-core,
      orthology-inferred regulatory context.
- term:
    id: GO:0009749
    label: response to glucose
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to glucose projected electronically from the rat ortholog (P12928)
      via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: Hepatic pyruvate kinase (L isoform) transcription is induced by dietary
      glucose/carbohydrate; this is a regulatory context transferred from the rat
      ortholog, not PKLR's molecular activity. Retained as non-core.
- term:
    id: GO:0010038
    label: response to metal ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to metal ion projected electronically from the rat ortholog
      (P12928) via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: Pyruvate kinase depends on Mg2+/Mn2+ and K+ as catalytic cofactors, so
      metal-ion sensitivity is biologically plausible, but this orthology-transferred
      biological-process term overlaps with the more precise metal-ion-binding molecular-function
      annotations and is peripheral to the core function. Retained as non-core.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Cellular insulin response projected electronically from the rat ortholog
      (P12928); reflects hormonal regulation of the liver isoform, not PKLR's molecular
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Duplicates the IBA cellular-response-to-insulin annotation via orthology
      transfer. It captures upstream insulin/glucagon regulation of hepatic pyruvate
      kinase expression and phosphorylation rather than a process PKLR itself performs;
      retained but flagged as an over-annotation.
- term:
    id: GO:0033198
    label: response to ATP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to ATP projected electronically from the rat ortholog (P12928)
      via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: ATP is both a product of the pyruvate kinase reaction and a classic allosteric
      inhibitor of the enzyme, so ATP-sensitivity is biologically real, but this orthology-transferred
      biological-process term is peripheral to the core catalytic function. Retained
      as non-core.
- term:
    id: GO:0042866
    label: pyruvate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Pyruvate biosynthesis projected electronically from the rat ortholog
      (P12928); an alternative process framing of the pyruvate kinase reaction, whose
      product is pyruvate.
    action: KEEP_AS_NON_CORE
    reason: Pyruvate is the direct product of the pyruvate kinase reaction, so this
      is a correct but redundant restatement of the glycolytic function. It duplicates
      the Reactome TAS pyruvate-biosynthetic-process annotation and is subsumed by
      the glycolytic-process core annotation; retained as non-core.
- term:
    id: GO:0048029
    label: monosaccharide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Monosaccharide binding projected electronically from the rat ortholog
      (P12928); likely a misleading generalization of fructose 1,6-bisphosphate allosteric
      binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: PKLR is allosterically activated by fructose 1,6-bisphosphate, a bisphosphorylated
      hexose, via a dedicated allosteric site. Generalizing this to broad monosaccharide
      binding is misleading (FBP is a phosphorylated sugar bisphosphate, not a free
      monosaccharide) and adds no informative molecular function. Retained but flagged
      as an over-annotation.
- term:
    id: GO:0051591
    label: response to cAMP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Response to cAMP projected electronically from the rat ortholog (P12928)
      via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: Glucagon raises hepatic cAMP, activating PKA, which phosphorylates and
      inhibits the liver pyruvate kinase isoform; cAMP-responsiveness is therefore
      biologically plausible but represents upstream regulation rather than PKLR's
      molecular function. Retained as non-core.
- term:
    id: GO:0071872
    label: cellular response to epinephrine stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Cellular epinephrine response projected electronically from the rat ortholog
      (P12928) via Ensembl Compara orthology.
    action: KEEP_AS_NON_CORE
    reason: Epinephrine, like glucagon, elevates cAMP/PKA signalling that regulates
      hepatic pyruvate kinase activity by phosphorylation; this is an orthology-transferred
      regulatory context peripheral to PKLR's core catalytic function. Retained as
      non-core.
- term:
    id: GO:0042866
    label: pyruvate biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70268
  qualifier: involved_in
  review:
    summary: Reactome-asserted involvement in pyruvate biosynthesis, reflecting that
      pyruvate is the product of the pyruvate kinase reaction.
    action: KEEP_AS_NON_CORE
    reason: Correct product-oriented framing of the same PEP -> pyruvate reaction that
      is captured more informatively by the glycolytic-process and pyruvate-kinase-activity
      core annotations. Retained as non-core to avoid redundancy with the core function.
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70171
  qualifier: involved_in
  review:
    summary: Reactome-asserted participation in canonical glycolysis (Embden-Meyerhof-Parnas
      pathway), the final ATP-generating step of which PKLR catalyses.
    action: ACCEPT
    reason: Canonical glycolysis is a precise subtype of glycolytic process describing
      the classic glucose-to-pyruvate EMP pathway, of which pyruvate kinase catalyses
      the terminal committed step. This accurately captures PKLR's biological process
      role.
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: EXP
  original_reference_id: PMID:11960989
  qualifier: enables
  review:
    summary: Experimentally demonstrated pyruvate kinase activity of human erythrocyte
      RPK, characterized structurally and kinetically together with disease mutants.
    action: ACCEPT
    reason: This study solved the crystal structure of human RPK in complex with fructose
      1,6-bisphosphate and a substrate analogue and functionally characterized wild-type
      and mutant enzymes, directly establishing the pyruvate kinase catalytic activity
      that is the core molecular function of PKLR.
    supported_by:
    - reference_id: PMID:11960989
      supporting_text: we have solved the 2.7 A resolution crystal structure of human
        RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and
        phosphoglycolate, a substrate analogue
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: EXP
  original_reference_id: PMID:15996096
  qualifier: enables
  review:
    summary: Pyruvate kinase activity supported by a structural/mechanistic study;
      the cited paper characterizes the human M2 isozyme (PKM gene), applied to PKLR
      by isozyme analogy via Reactome.
    action: ACCEPT
    reason: 'The pyruvate kinase catalytic activity assignment is correct for PKLR
      and independently established by human RPK biochemistry (PMID:11960989). This
      particular Reactome-sourced EXP citation is the PKM2 crystallography paper (a
      paralog); the catalytic mechanism, cofactor (Mg2+/K+) and FBP allostery are
      conserved across the L/R/M1/M2 isozymes, so it does not conflict with the annotation.
      Per curation policy the experimental annotation is retained rather than removed;
      reference relevance is flagged as MEDIUM (paralog-derived).'
    supported_by:
    - reference_id: PMID:15996096
      supporting_text: The X-ray structure of human hPKM2 complexed with Mg(2+), K(+),
        the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PKLR in urinary exosomes; a common
      MS finding for abundant cytosolic enzymes rather than a functional location.
    action: KEEP_AS_NON_CORE
    reason: Detection in an exosome/extracellular-vesicle proteome is a frequent incidental
      finding for highly abundant soluble glycolytic enzymes and does not reflect
      where PKLR performs its catalytic function (the cytosol). Retained as a non-core
      localization observation.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: we used LC-MS/MS to profile the proteome of human urinary exosomes
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71670
  qualifier: located_in
  review:
    summary: Reactome-asserted cytosolic localization, the compartment where PKLR
      catalyses the glycolytic pyruvate kinase reaction.
    action: ACCEPT
    reason: PKLR is a soluble cytosolic enzyme; glycolysis occurs in the cytosol and
      the pyruvate kinase step is cytosolic. This is the informative subcellular location
      and represents the core cellular component for the gene product.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9727857
  qualifier: located_in
  review:
    summary: Reactome-asserted cytosolic localization (from a SARS-CoV-1 host-interaction
      model), consistent with PKLR being a soluble cytosolic enzyme.
    action: ACCEPT
    reason: Duplicate cytosol localization from a different Reactome reaction; correct
      and consistent with the primary glycolysis-based cytosol annotation. Cytosol
      is the core cellular component for PKLR.
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: TAS
  original_reference_id: PMID:3126495
  qualifier: enables
  review:
    summary: Author-stated pyruvate kinase activity from the study that cloned and
      expressed human liver (L)-type PK, detecting enzymatic activity in transfected
      cells.
    action: ACCEPT
    reason: This paper determined the full-length human L-type PK cDNA and expressed
      it in COS cells, where L-type PK activity was detected, corroborating the core
      pyruvate kinase molecular function of PKLR.
    supported_by:
    - reference_id: PMID:3126495
      supporting_text: Human L-type PK activity was detected in the extract of COS
        cells by the classical PK electrophoresis method.
- term:
    id: GO:0004743
    label: pyruvate kinase activity
  evidence_type: NAS
  original_reference_id: PMID:1445295
  qualifier: enables
  review:
    summary: Non-traceable author statement of pyruvate kinase identity from a study
      of the human PK L-gene structure and its erythroid promoter.
    action: ACCEPT
    reason: This paper characterizes the human pyruvate kinase L-gene (12 exons, R-
      and L-type transcripts from alternative first exons) and its promoter; the pyruvate
      kinase activity assignment is correct for the gene, though the evidence here
      is genomic/promoter rather than a direct activity assay. Consistent with the
      stronger EXP/TAS evidence, so accepted.
    supported_by:
    - reference_id: PMID:1445295
      supporting_text: The human pyruvate kinase (PK) L-gene is organized in 12 exons
        over 9.5
core_functions:
- description: Catalyses the final, committed, essentially irreversible ATP-generating
    step of glycolysis, transferring phosphate from phosphoenolpyruvate to ADP to
    form pyruvate and ATP (EC 2.7.1.40), requiring Mg2+/Mn2+ and K+ as cofactors and
    allosterically activated by fructose 1,6-bisphosphate.
  molecular_function:
    id: GO:0004743
    label: pyruvate kinase activity
  directly_involved_in:
  - id: GO:0006096
    label: glycolytic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:11960989
    supporting_text: we have solved the 2.7 A resolution crystal structure of human
      RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and
      phosphoglycolate, a substrate analogue
  - reference_id: file:human/PKLR/PKLR-uniprot.txt
    supporting_text: Pyruvate kinase that catalyzes the conversion of
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/PKLR/PKLR-uniprot.txt
  title: UniProtKB P30613 (KPYR_HUMAN) Pyruvate kinase PKLR
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary source record for PKLR function, catalytic activity (EC
      2.7.1.40), Mg2+/Mn2+/K+ cofactors, FBP allosteric activation, homotetramer,
      glycolysis pathway, and CNSHA2/PKHYP disease associations.
- id: PMID:11960989
  title: Structure and function of human erythrocyte pyruvate kinase. Molecular basis
    of nonspherocytic hemolytic anemia.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Crystal structure and functional characterization of human erythrocyte
      RPK with FBP and a substrate analogue; establishes catalytic activity, cofactors,
      allostery, and links CNSHA2 mutations to enzyme defects.
- id: PMID:1445295
  title: Structural analysis of human pyruvate kinase L-gene and identification of
    the promoter activity in erythroid cells.
  findings: []
- id: PMID:15996096
  title: Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Structure/mechanism paper on the human M2 isozyme (PKM gene), not
      PKLR. Used by Reactome to support pyruvate kinase activity for PKLR by isozyme
      analogy; the catalytic mechanism and Mg2+/K+/FBP dependence are conserved across
      the L/R/M1/M2 isozymes, so it corroborates but is not a direct PKLR study.
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput urinary exosome proteomics; supports the incidental
      extracellular-exosome localization (HDA) but not PKLR's core catalytic function.
      PKLR is not individually discussed in the abstract.
- id: PMID:3126495
  title: 'Human liver type pyruvate kinase: complete amino acid sequence and the expression
    in mammalian cells.'
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HuRI systematic yeast two-hybrid interactome; source of the single
      PKLR-CPNE7 (Q9UBL6-2) protein-binding IPI. High-throughput, no PKLR-specific
      functional characterization; underlies an uninformative bare protein-binding
      annotation flagged as over-annotated.
- id: Reactome:R-HSA-70171
  title: Glycolysis
  findings: []
- id: Reactome:R-HSA-70268
  title: Pyruvate metabolism
  findings: []
- id: Reactome:R-HSA-71670
  title: Pyruvate kinase dephosphorylates PEP to PYR
  findings: []
- id: Reactome:R-HSA-9727857
  title: SARS-CoV-1 SUMO1-K62-p-S177-N dimer binds to PKL
  findings: []

PKLR

Gene Description