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Protein

Pyruvate kinase PKM

Gene

PKM

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation (By similarity).By similarity

Catalytic activityi

ATP + pyruvate = ADP + phosphoenolpyruvate.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2 (By similarity).By similarity

Pathwayi: glycolysis

This protein is involved in step 5 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate.
Proteins known to be involved in the 5 steps of the subpathway in this organism are:
  1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (GAPDHS), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase (GAPDHS)
  2. no protein annotated in this organism
  3. no protein annotated in this organism
  4. Beta-enolase (ENO3)
  5. Pyruvate kinase (PKLR), Pyruvate kinase (PKM), Pyruvate kinase (PKLR), Pyruvate kinase (pklr), Pyruvate kinase PKM (PKM)
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei70SerineBy similarity1
Binding sitei73SubstrateBy similarity1
Metal bindingi75PotassiumBy similarity1
Metal bindingi77PotassiumBy similarity1
Binding sitei106SerineBy similarity1
Metal bindingi113PotassiumBy similarity1
Metal bindingi114Potassium; via carbonyl oxygenBy similarity1
Sitei270Transition state stabilizerBy similarity1
Metal bindingi272MagnesiumBy similarity1
Binding sitei295Substrate; via amide nitrogenBy similarity1
Metal bindingi296MagnesiumBy similarity1
Binding sitei296Substrate; via amide nitrogenBy similarity1
Binding sitei328SubstrateBy similarity1
Binding sitei464SerineBy similarity1
Binding sitei482D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity1
Binding sitei489D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity1

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Pyruvate

Enzyme and pathway databases

BRENDAi2.7.1.40. 1749.
SABIO-RKP11974.
UniPathwayiUPA00109; UER00188.

Names & Taxonomyi

Protein namesi
Recommended name:
Pyruvate kinase PKM (EC:2.7.1.40)
Alternative name(s):
Pyruvate kinase muscle isozyme
Gene namesi
Name:PKM
Synonyms:PKM2
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic activity.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5637.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001120912 – 531Pyruvate kinase PKMAdd BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei3N6,N6,N6-trimethyllysineBy similarity1
Modified residuei37PhosphoserineBy similarity1
Modified residuei41PhosphothreonineBy similarity1
Modified residuei62N6-acetyllysineBy similarity1
Modified residuei66N6-succinyllysineBy similarity1
Modified residuei89N6-acetyllysineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei105PhosphotyrosineBy similarity1
Modified residuei127PhosphoserineBy similarity1
Modified residuei148PhosphotyrosineBy similarity1
Modified residuei166N6-acetyllysine; alternateBy similarity1
Modified residuei166N6-succinyllysine; alternateBy similarity1
Cross-linki166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Modified residuei175PhosphotyrosineBy similarity1
Modified residuei195PhosphothreonineBy similarity1
Modified residuei266N6-acetyllysineBy similarity1
Modified residuei270N6-acetyllysineBy similarity1
Modified residuei305N6-acetyllysineBy similarity1
Modified residuei322N6-acetyllysine; alternateBy similarity1
Modified residuei322N6-succinyllysine; alternateBy similarity1
Modified residuei475N6-acetyllysineBy similarity1
Modified residuei498N6-succinyllysineBy similarity1

Post-translational modificationi

ISGylated.By similarity
Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP11974.

Interactioni

Subunit structurei

Monomer and homotetramer. Exists as a monomer in the absence of fructose 1,6 bi-phosphate (FBP), and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds T3. Tetramer formation induces pyruvate kinase activity. FBP stimulates the formation of tetramers from dimers. Interacts with HERC1, POU5F1 and PML. Interacts (isoform M2) with EGLN3; the interaction hydroxylates PKM under hypoxia and enhances binding to HIF1A. Interacts (isoform M2) with HIF1A; the interaction is enhanced by binding of EGLN3, promoting enhanced transcription activity under hypoxia (By similarity). Interacts (isoform M2, but not isoform M1) with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CKMP005632EBI-7133357,EBI-2750756

Protein-protein interaction databases

DIPiDIP-47514N.
IntActiP11974. 1 interactor.
MINTiMINT-6824949.

Structurei

Secondary structure

1531
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi18 – 21Combined sources4
Helixi26 – 31Combined sources6
Beta strandi45 – 50Combined sources6
Turni53 – 55Combined sources3
Helixi58 – 67Combined sources10
Beta strandi71 – 75Combined sources5
Helixi81 – 96Combined sources16
Turni97 – 100Combined sources4
Turni102 – 104Combined sources3
Beta strandi109 – 113Combined sources5
Beta strandi119 – 121Combined sources3
Beta strandi126 – 128Combined sources3
Beta strandi130 – 134Combined sources5
Beta strandi139 – 143Combined sources5
Helixi146 – 148Combined sources3
Beta strandi154 – 160Combined sources7
Helixi164 – 167Combined sources4
Beta strandi173 – 176Combined sources4
Turni177 – 180Combined sources4
Beta strandi181 – 189Combined sources9
Beta strandi192 – 199Combined sources8
Beta strandi201 – 203Combined sources3
Beta strandi208 – 210Combined sources3
Beta strandi212 – 214Combined sources3
Helixi223 – 234Combined sources12
Beta strandi238 – 242Combined sources5
Helixi248 – 258Combined sources11
Turni259 – 264Combined sources6
Beta strandi265 – 271Combined sources7
Helixi274 – 278Combined sources5
Helixi280 – 286Combined sources7
Beta strandi287 – 293Combined sources7
Helixi294 – 300Combined sources7
Helixi303 – 305Combined sources3
Helixi306 – 320Combined sources15
Beta strandi324 – 329Combined sources6
Helixi332 – 335Combined sources4
Beta strandi337 – 339Combined sources3
Helixi342 – 354Combined sources13
Beta strandi357 – 362Combined sources6
Helixi363 – 366Combined sources4
Helixi371 – 387Combined sources17
Helixi391 – 401Combined sources11
Turni402 – 404Combined sources3
Helixi408 – 423Combined sources16
Beta strandi428 – 431Combined sources4
Beta strandi433 – 435Combined sources3
Helixi436 – 443Combined sources8
Beta strandi450 – 455Combined sources6
Helixi457 – 462Combined sources6
Helixi463 – 465Combined sources3
Beta strandi469 – 473Combined sources5
Helixi482 – 499Combined sources18
Beta strandi508 – 513Combined sources6
Beta strandi515 – 518Combined sources4
Beta strandi524 – 529Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A49X-ray2.10A/B/C/D/E/F/G/H2-531[»]
1A5UX-ray2.35A/B/C/D/E/F/G/H2-531[»]
1AQFX-ray2.70A/B/C/D/E/F/G/H2-531[»]
1F3WX-ray3.00A/B/C/D/E/F/G/H2-531[»]
1F3XX-ray2.80A/B/C/D/E/F/G/H2-531[»]
1PKNX-ray2.90A2-531[»]
2G50X-ray1.65A/B/C/D/E/F/G/H2-531[»]
3N25X-ray2.41A/B/C/D/E/F/G/H1-531[»]
ProteinModelPortaliP11974.
SMRiP11974.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11974.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni307 – 531Interaction with POU5F1By similarityAdd BLAST225
Regioni432 – 437D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity6
Regioni514 – 521D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity8

Sequence similaritiesi

Belongs to the pyruvate kinase family.Curated

Phylogenomic databases

HOGENOMiHOG000021559.
HOVERGENiHBG000941.
InParanoidiP11974.
KOiK00873.

Family and domain databases

Gene3Di2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProiIPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
IPR011037. Pyrv_Knase-like_insert_dom.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR015793. Pyrv_Knase_brl.
IPR015795. Pyrv_Knase_C.
IPR015806. Pyrv_Knase_insert_dom.
[Graphical view]
PANTHERiPTHR11817. PTHR11817. 1 hit.
PfamiPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSiPR01050. PYRUVTKNASE.
SUPFAMiSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsiTIGR01064. pyruv_kin. 1 hit.
PROSITEiPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform M1 (identifier: P11974-1) [UniParc]FASTAAdd to basket
Also known as: PKM1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSKSHSEAGS AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT
60 70 80 90 100
IGPASRSVET LKEMIKSGMN VARMNFSHGT HEYHAETIKN VRTATESFAS
110 120 130 140 150
DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENILWLD YKNICKVVDV GSKVYVDDGL ISLQVKQKGP DFLVTEVENG
210 220 230 240 250
GFLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKAAD
260 270 280 290 300
VHEVRKILGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
310 320 330 340 350
IPAEKVFLAQ KMIIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN
360 370 380 390 400
AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELAR
410 420 430 440 450
SSSHSTDLME AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNHQTA RQAHLYRGIF PVVCKDPVQE AWAEDVDLRV NLAMNVGKAR
510 520 530
GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
Length:531
Mass (Da):58,048
Last modified:January 23, 2007 - v4
Checksum:iAC0AFB579FC505E6
GO
Isoform M2 (identifier: P11974-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: PKM2

The sequence of this isoform differs from the canonical sequence as follows:
     389-433: MFHRKLFEEL...LAAALIVLTE → IYHLQLFEEL...CSGAIIVLTK

Show »
Length:531
Mass (Da):57,905
Checksum:i5BCA6BC40C2FCA2D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti401S → A in AAC48536 (PubMed:8626426).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011106389 – 433MFHRK…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09028 mRNA. Translation: AAB61963.1.
U44751 mRNA. Translation: AAC48536.1.
AF032389 mRNA. Translation: AAB86587.1.
PIRiA28506.
A54113.
RefSeqiNP_001182573.1. NM_001195644.1.
NP_001182574.1. NM_001195645.1. [P11974-2]
UniGeneiOcu.2156.

Genome annotation databases

GeneIDi100008676.
KEGGiocu:100008676.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Worthington enzyme manual

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09028 mRNA. Translation: AAB61963.1.
U44751 mRNA. Translation: AAC48536.1.
AF032389 mRNA. Translation: AAB86587.1.
PIRiA28506.
A54113.
RefSeqiNP_001182573.1. NM_001195644.1.
NP_001182574.1. NM_001195645.1. [P11974-2]
UniGeneiOcu.2156.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A49X-ray2.10A/B/C/D/E/F/G/H2-531[»]
1A5UX-ray2.35A/B/C/D/E/F/G/H2-531[»]
1AQFX-ray2.70A/B/C/D/E/F/G/H2-531[»]
1F3WX-ray3.00A/B/C/D/E/F/G/H2-531[»]
1F3XX-ray2.80A/B/C/D/E/F/G/H2-531[»]
1PKNX-ray2.90A2-531[»]
2G50X-ray1.65A/B/C/D/E/F/G/H2-531[»]
3N25X-ray2.41A/B/C/D/E/F/G/H1-531[»]
ProteinModelPortaliP11974.
SMRiP11974.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-47514N.
IntActiP11974. 1 interactor.
MINTiMINT-6824949.

Chemistry databases

ChEMBLiCHEMBL5637.

Proteomic databases

PRIDEiP11974.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008676.
KEGGiocu:100008676.

Organism-specific databases

CTDi5315.

Phylogenomic databases

HOGENOMiHOG000021559.
HOVERGENiHBG000941.
InParanoidiP11974.
KOiK00873.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00188.
BRENDAi2.7.1.40. 1749.
SABIO-RKP11974.

Miscellaneous databases

EvolutionaryTraceiP11974.

Family and domain databases

Gene3Di2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProiIPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
IPR011037. Pyrv_Knase-like_insert_dom.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR015793. Pyrv_Knase_brl.
IPR015795. Pyrv_Knase_C.
IPR015806. Pyrv_Knase_insert_dom.
[Graphical view]
PANTHERiPTHR11817. PTHR11817. 1 hit.
PfamiPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSiPR01050. PYRUVTKNASE.
SUPFAMiSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsiTIGR01064. pyruv_kin. 1 hit.
PROSITEiPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPYM_RABIT
AccessioniPrimary (citable) accession number: P11974
Secondary accession number(s): O18919, Q29501
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 157 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

There are 4 isozymes of pyruvate kinase in mammals (L, R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L and R isozymes are generated from the PKLR by differential splicing of RNA; the M1 and M2 forms are produced from the PKM gene by differential splicing. 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 as well as in most cancer cells.

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.