UniProtKB - P11980 (KPYM_RAT)
Pyruvate kinase PKM
Pkm
Functioni
Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
By similarityIsoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity. In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase. Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase. Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription. Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (By similarity).
Promotes the expression of the immune checkpoint protein CD274 in ARNTL/BMAL1-deficient macrophages. May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity).
Plays a role in caspase independent cell death of tumor cells (By similarity).
By similarityPyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth. In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.
By similarityMiscellaneous
Catalytic activityi
- EC:2.7.1.40By similarity EC:2.7.1.40By similarityThis reaction proceeds in the backwardBy similarity direction.
- EC:2.7.10.2By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:2.7.11.1By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Protein has several cofactor binding sites:Activity regulationi
: glycolysis Pathwayi
This protein is involved in step 5 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate.By similarity This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.View all proteins of this organism that are known to be involved in the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate, the pathway glycolysis and in Carbohydrate degradation.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 70 | SerineBy similarity | 1 | |
Binding sitei | 73 | SubstrateBy similarity | 1 | |
Metal bindingi | 75 | PotassiumBy similarity | 1 | |
Metal bindingi | 77 | PotassiumBy similarity | 1 | |
Binding sitei | 106 | SerineBy similarity | 1 | |
Metal bindingi | 113 | PotassiumBy similarity | 1 | |
Metal bindingi | 114 | Potassium; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 120 | ATPBy similarity | 1 | |
Binding sitei | 207 | ATPBy similarity | 1 | |
Binding sitei | 270 | Substrate; via amide nitrogenBy similarity | 1 | |
Sitei | 270 | Transition state stabilizerBy similarity | 1 | |
Metal bindingi | 272 | MagnesiumBy similarity | 1 | |
Binding sitei | 295 | Substrate; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 296 | MagnesiumBy similarity | 1 | |
Binding sitei | 296 | Substrate; via amide nitrogenBy similarity | 1 | |
Binding sitei | 328 | SubstrateBy similarity | 1 | |
Binding sitei | 464 | SerineBy similarity | 1 | |
Binding sitei | 482 | D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity | 1 | |
Binding sitei | 489 | D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 75 – 78 | ATPBy similarity | 4 |
GO - Molecular functioni
- ADP binding Source: RGD
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: CAFA
- kinase activity Source: UniProtKB-KW
- magnesium ion binding Source: InterPro
- mRNA binding Source: UniProtKB
- potassium ion binding Source: InterPro
- pyruvate kinase activity Source: CAFA
- thyroid hormone binding Source: CAFA
GO - Biological processi
- animal organ regeneration Source: RGD
- ATP biosynthetic process Source: RGD
- cellular response to insulin stimulus Source: GO_Central
- glucose metabolic process Source: RGD
- glycolytic process Source: CAFA
- liver development Source: RGD
- positive regulation of cytoplasmic translation Source: UniProtKB
- positive regulation of sprouting angiogenesis Source: UniProtKB
- programmed cell death Source: RGD
- pyruvate biosynthetic process Source: RGD
- response to gravity Source: RGD
- response to hypoxia Source: RGD
- response to insulin Source: RGD
- response to muscle inactivity Source: RGD
- response to nutrient Source: RGD
- response to organic substance Source: RGD
- skeletal muscle tissue regeneration Source: RGD
Keywordsi
Molecular function | Allosteric enzyme, Kinase, Transferase |
Biological process | Glycolysis, Translation regulation |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Pyruvate |
Enzyme and pathway databases
SABIO-RKi | P11980 |
UniPathwayi | UPA00109;UER00188 |
Protein family/group databases
MoonProti | P11980 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Pkm Synonyms:Pkm2, Pykm |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3337, Pkm |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Endoplasmic reticulum
- rough endoplasmic reticulum Source: UniProtKB
Nucleus
- nucleus Source: RGD
Other locations
- cilium Source: RGD
- cytoplasm Source: GO_Central
- pyruvate kinase complex Source: CAFA
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000112092 | 1 – 531 | Pyruvate kinase PKMAdd BLAST | 531 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 3 | N6,N6,N6-trimethyllysineBy similarity | 1 | |
Modified residuei | 37 | PhosphoserineBy similarity | 1 | |
Modified residuei | 41 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 62 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 66 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 89 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 97 | PhosphoserineCombined sources | 1 | |
Modified residuei | 100 | PhosphoserineCombined sources | 1 | |
Modified residuei | 105 | PhosphotyrosineBy similarity | 1 | |
Cross-linki | 115 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 127 | PhosphoserineBy similarity | 1 | |
Modified residuei | 148 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 166 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 166 | N6-succinyllysine; alternateBy similarity | 1 | |
Cross-linki | 166 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity | ||
Modified residuei | 175 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 195 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 266 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 266 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity | ||
Modified residuei | 270 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 270 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity | ||
Modified residuei | 305 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 322 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 322 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 408 | 4-hydroxyprolineBy similarity | 1 | |
Modified residuei | 475 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 498 | N6-succinyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Hydroxylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | P11980 |
PaxDbi | P11980 |
PRIDEi | P11980 |
2D gel databases
World-2DPAGEi | 0004:P11980 |
PTM databases
iPTMneti | P11980 |
PhosphoSitePlusi | P11980 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000011329, Expressed in skeletal muscle tissue and 21 other tissues |
ExpressionAtlasi | P11980, baseline and differential |
Genevisiblei | P11980, RN |
Interactioni
Subunit structurei
Monomer and homotetramer; exists as a monomer in the absence of D-fructose 1,6-bisphosphate (FBP), and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds 3,3',5-triiodo-L-thyronine (T3). Tetramer formation induces pyruvate kinase activity. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. FBP stimulates the formation of tetramers from dimers. Homodimer; exists in a dimeric form in tumor cells and the dimeric form has less affinity for the phosphoenolpyruvate substrate. The homodimer converts into a protein kinase.
Interacts with HERC1, POU5F1 and PML.
Interacts with EGLN3; the interaction hydroxylates PKM under hypoxia and enhances binding to HIF1A.
Interacts with HIF1A; the interaction is enhanced by binding of EGLN3, promoting enhanced transcription activity under hypoxia.
Interacts with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation.
Interacts with JMJD8.
Interacts with TRAF4.
Interacts with (phosphorylated) CTNNB1; leading to activate transcription.
By similarityGO - Molecular functioni
- identical protein binding Source: CAFA
Protein-protein interaction databases
BioGRIDi | 247659, 8 interactors |
CORUMi | P11980 |
IntActi | P11980, 6 interactors |
MINTi | P11980 |
STRINGi | 10116.ENSRNOP00000015331 |
Chemistry databases
BindingDBi | P11980 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 307 – 531 | Interaction with POU5F1By similarityAdd BLAST | 225 | |
Regioni | 389 – 433 | Intersubunit contactAdd BLAST | 45 | |
Regioni | 432 – 437 | D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity | 6 | |
Regioni | 516 – 521 | D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity | 6 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2323, Eukaryota |
GeneTreei | ENSGT00390000008859 |
HOGENOMi | CLU_015439_0_1_1 |
InParanoidi | P11980 |
OMAi | QVPIVQK |
OrthoDBi | 933620at2759 |
PhylomeDBi | P11980 |
TreeFami | TF300390 |
Family and domain databases
CDDi | cd00288, Pyruvate_Kinase, 1 hit |
Gene3Di | 2.40.33.10, 1 hit 3.20.20.60, 1 hit 3.40.1380.20, 2 hits |
InterProi | View protein in InterPro IPR001697, Pyr_Knase IPR015813, Pyrv/PenolPyrv_Kinase-like_dom IPR040442, Pyrv_Kinase-like_dom_sf IPR011037, Pyrv_Knase-like_insert_dom_sf IPR018209, Pyrv_Knase_AS IPR015793, Pyrv_Knase_brl IPR015795, Pyrv_Knase_C IPR036918, Pyrv_Knase_C_sf IPR015806, Pyrv_Knase_insert_dom_sf |
PANTHERi | PTHR11817, PTHR11817, 1 hit |
Pfami | View protein in Pfam PF00224, PK, 1 hit PF02887, PK_C, 1 hit |
PRINTSi | PR01050, PYRUVTKNASE |
SUPFAMi | SSF50800, SSF50800, 1 hit SSF51621, SSF51621, 1 hit SSF52935, SSF52935, 1 hit |
TIGRFAMsi | TIGR01064, pyruv_kin, 1 hit |
PROSITEi | View protein in PROSITE PS00110, PYRUVATE_KINASE, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT
60 70 80 90 100
IGPASRSVEM LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS
110 120 130 140 150
DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKEKGA DYLVTEVENG
210 220 230 240 250
GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKAAD
260 270 280 290 300
VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
310 320 330 340 350
IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN
360 370 380 390 400
AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAVF HRLLFEELAR
410 420 430 440 450
ASSQSTDPLE AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD AWAEDVDLRV NLAMNVGKAR
510 520 530
GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
The sequence of this isoform differs from the canonical sequence as follows:
389-433: VFHRLLFEEL...LAAALIVLTE → IYHLQLFEEL...CSGAIIVLTK
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2JVG3 | A0A0G2JVG3_RAT | Pyruvate kinase | Pkm | 612 | Annotation score: | ||
A0A8I6ABE3 | A0A8I6ABE3_RAT | Pyruvate kinase PKM | Pkm | 591 | Annotation score: | ||
A0A8I6G5T6 | A0A8I6G5T6_RAT | Pyruvate kinase PKM | Pkm | 591 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_011107 | 389 – 433 | VFHRL…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2. CuratedAdd BLAST | 45 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M24359 Genomic DNA Translation: AAB93666.1 M24359 Genomic DNA Translation: AAB93667.1 M14377 Genomic DNA No translation available. X15800 mRNA Translation: CAA33799.1 |
PIRi | A26186 B26186 |
RefSeqi | NP_445749.1, NM_053297.2 [P11980-1] XP_006243250.2, XM_006243188.3 [P11980-2] |
Genome annotation databases
GeneIDi | 25630 |
KEGGi | rno:25630 |
UCSCi | RGD:3337, rat [P11980-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M24359 Genomic DNA Translation: AAB93666.1 M24359 Genomic DNA Translation: AAB93667.1 M14377 Genomic DNA No translation available. X15800 mRNA Translation: CAA33799.1 |
PIRi | A26186 B26186 |
RefSeqi | NP_445749.1, NM_053297.2 [P11980-1] XP_006243250.2, XM_006243188.3 [P11980-2] |
3D structure databases
AlphaFoldDBi | P11980 |
SMRi | P11980 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 247659, 8 interactors |
CORUMi | P11980 |
IntActi | P11980, 6 interactors |
MINTi | P11980 |
STRINGi | 10116.ENSRNOP00000015331 |
Chemistry databases
BindingDBi | P11980 |
ChEMBLi | CHEMBL4994 |
Protein family/group databases
MoonProti | P11980 |
PTM databases
iPTMneti | P11980 |
PhosphoSitePlusi | P11980 |
2D gel databases
World-2DPAGEi | 0004:P11980 |
Proteomic databases
jPOSTi | P11980 |
PaxDbi | P11980 |
PRIDEi | P11980 |
Protocols and materials databases
DNASUi | 25630 |
Genome annotation databases
GeneIDi | 25630 |
KEGGi | rno:25630 |
UCSCi | RGD:3337, rat [P11980-1] |
Organism-specific databases
CTDi | 5315 |
RGDi | 3337, Pkm |
Phylogenomic databases
eggNOGi | KOG2323, Eukaryota |
GeneTreei | ENSGT00390000008859 |
HOGENOMi | CLU_015439_0_1_1 |
InParanoidi | P11980 |
OMAi | QVPIVQK |
OrthoDBi | 933620at2759 |
PhylomeDBi | P11980 |
TreeFami | TF300390 |
Enzyme and pathway databases
UniPathwayi | UPA00109;UER00188 |
SABIO-RKi | P11980 |
Miscellaneous databases
PROi | PR:P11980 |
Gene expression databases
Bgeei | ENSRNOG00000011329, Expressed in skeletal muscle tissue and 21 other tissues |
ExpressionAtlasi | P11980, baseline and differential |
Genevisiblei | P11980, RN |
Family and domain databases
CDDi | cd00288, Pyruvate_Kinase, 1 hit |
Gene3Di | 2.40.33.10, 1 hit 3.20.20.60, 1 hit 3.40.1380.20, 2 hits |
InterProi | View protein in InterPro IPR001697, Pyr_Knase IPR015813, Pyrv/PenolPyrv_Kinase-like_dom IPR040442, Pyrv_Kinase-like_dom_sf IPR011037, Pyrv_Knase-like_insert_dom_sf IPR018209, Pyrv_Knase_AS IPR015793, Pyrv_Knase_brl IPR015795, Pyrv_Knase_C IPR036918, Pyrv_Knase_C_sf IPR015806, Pyrv_Knase_insert_dom_sf |
PANTHERi | PTHR11817, PTHR11817, 1 hit |
Pfami | View protein in Pfam PF00224, PK, 1 hit PF02887, PK_C, 1 hit |
PRINTSi | PR01050, PYRUVTKNASE |
SUPFAMi | SSF50800, SSF50800, 1 hit SSF51621, SSF51621, 1 hit SSF52935, SSF52935, 1 hit |
TIGRFAMsi | TIGR01064, pyruv_kin, 1 hit |
PROSITEi | View protein in PROSITE PS00110, PYRUVATE_KINASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KPYM_RAT | |
Accessioni | P11980Primary (citable) accession number: P11980 Secondary accession number(s): P11981 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1989 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 195 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families