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Protein

Pyruvate kinase PKM

Gene

PKM

Organism
Homo sapiens (Human)
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. Plays a general role in caspase independent cell death of tumor cells. 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.3 Publications

Catalytic activityi

ATP + pyruvate = ADP + phosphoenolpyruvate.2 Publications

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 M2.6 Publications

Kineticsi

  1. KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0)2 Publications
  2. KM=0.17 mM for phosphoenolpyruvate (in the presence of 2 mM D-fructose 1,6-bisphosphate (FBP), at 32 degrees Celsius, pH 8.0)2 Publications
  3. KM=0.34 mM for ADP (at 32 degrees Celsius, pH 8.0)2 Publications
  4. KM=0.24 mM for ADP (in the presence of 2 mM FBP, at 32 degrees Celsius, pH 8.0)2 Publications
  5. KM=0.13 mM for phosphoenolpyruvate (in the presence of 2 mM FBP, at 25 degrees Celsius)2 Publications
  6. KM=0.63 mM for ADP (in the presence of 2 mM FBP, at 25 degrees Celsius)2 Publications

    pH dependencei

    Optimum pH for T3 binding is 6.0-6.5. Increase in pH causes T3 binding to drop, does not bind T3 above pH 9.0 or below pH 5.0.2 Publications

    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, Glyceraldehyde-3-phosphate dehydrogenase (HEL-S-162eP), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (HEL-S-278), Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (GAPDHS)
    2. Phosphoglycerate kinase 2 (PGK2), Phosphoglycerate kinase 1 (PGK1)
    3. no protein annotated in this organism
    4. Beta-enolase (ENO3), Alpha-enolase (ENO1), Enolase 4 (ENO4), Gamma-enolase (ENO2)
    5. Pyruvate kinase, Pyruvate kinase PKM (PKM), Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase, Pyruvate kinase (PKM), Pyruvate kinase, Pyruvate kinase PKLR (PKLR), Pyruvate kinase, Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase (HEL-S-30), Pyruvate kinase (PKM2)
    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 sitei70Serine1
    Binding sitei73SubstrateBy similarity1
    Metal bindingi75PotassiumCombined sources1 Publication1
    Metal bindingi77PotassiumCombined sources1 Publication1
    Binding sitei106Serine1
    Metal bindingi113PotassiumCombined sources1 Publication1
    Metal bindingi114Potassium; via carbonyl oxygenCombined sources1 Publication1
    Binding sitei120ATPCombined sources1 Publication1
    Binding sitei207ATPCombined sources1 Publication1
    Binding sitei270Substrate; via amide nitrogenBy similarity1
    Sitei270Transition state stabilizerBy similarity1
    Metal bindingi272MagnesiumCombined sources1 Publication1
    Binding sitei295Substrate; via amide nitrogenBy similarity1
    Metal bindingi296MagnesiumCombined sources1 Publication1
    Binding sitei296Substrate; via amide nitrogenBy similarity1
    Binding sitei328SubstrateBy similarity1
    Sitei433Crucial for phosphotyrosine binding1
    Binding sitei464Serine1
    Binding sitei482D-fructose 1,6-bisphosphate; part of allosteric siteCombined sources2 Publications1
    Binding sitei489D-fructose 1,6-bisphosphate; part of allosteric siteCombined sources2 Publications1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi75 – 78ATPCombined sources1 Publication4

    GO - Molecular functioni

    • ADP binding Source: Ensembl
    • ATP binding Source: UniProtKB-KW
    • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
    • kinase activity Source: UniProtKB-KW
    • magnesium ion binding Source: InterPro
    • MHC class II protein complex binding Source: UniProtKB
    • poly(A) RNA binding Source: UniProtKB
    • potassium ion binding Source: InterPro
    • pyruvate kinase activity Source: UniProtKB

    GO - Biological processi

    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

    BioCyciMetaCyc:HS00906-MONOMER.
    ZFISH:HS00906-MONOMER.
    BRENDAi2.7.1.40. 2681.
    ReactomeiR-HSA-6798695. Neutrophil degranulation.
    R-HSA-70171. Glycolysis.
    SABIO-RKP14618.
    SIGNORiP14618.
    UniPathwayiUPA00109; UER00188.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pyruvate kinase PKM (EC:2.7.1.40)
    Alternative name(s):
    Cytosolic thyroid hormone-binding protein
    Short name:
    CTHBP
    Opa-interacting protein 3
    Short name:
    OIP-3
    Pyruvate kinase 2/3
    Pyruvate kinase muscle isozyme
    Thyroid hormone-binding protein 1
    Short name:
    THBP1
    Tumor M2-PK
    p58
    Gene namesi
    Name:PKM
    Synonyms:OIP3, PK2, PK3, PKM2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:9021. PKM.

    Subcellular locationi

    • Cytoplasm 1 Publication
    • Nucleus

    • 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.

    GO - Cellular componenti

    • cell-cell adherens junction Source: BHF-UCL
    • cilium Source: Ensembl
    • cytoplasm Source: UniProtKB
    • cytosol Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    • extracellular matrix Source: UniProtKB
    • extracellular vesicle Source: UniProtKB
    • mitochondrion Source: UniProtKB
    • myelin sheath Source: Ensembl
    • nucleus Source: UniProtKB
    • plasma membrane Source: HPA
    • vesicle Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi403P → A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-408. 1 Publication1
    Mutagenesisi408P → A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-403. 1 Publication1
    Mutagenesisi437S → Y: Unable to bind FBP but still activated by serine. 1 Publication1
    Mutagenesisi464H → A: Abolishes serine binding and allosteric activation. 1 Publication1

    Organism-specific databases

    DisGeNETi5315.
    OpenTargetsiENSG00000067225.
    PharmGKBiPA33353.

    Chemistry databases

    ChEMBLiCHEMBL1075189.
    DrugBankiDB00119. Pyruvic acid.

    Polymorphism and mutation databases

    BioMutaiPKM.
    DMDMi20178296.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources3 Publications
    ChainiPRO_00001120882 – 531Pyruvate kinase PKMAdd BLAST530

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserineCombined sources1 Publication1
    Modified residuei3N6,N6,N6-trimethyllysineCombined sources1
    Modified residuei37PhosphoserineCombined sources1
    Modified residuei41PhosphothreonineCombined sources1
    Modified residuei62N6-acetyllysineCombined sources1
    Modified residuei66N6-succinyllysineBy similarity1
    Modified residuei89N6-acetyllysineCombined sources1
    Modified residuei97PhosphoserineBy similarity1
    Modified residuei100PhosphoserineBy similarity1
    Modified residuei105PhosphotyrosineCombined sources1
    Modified residuei127PhosphoserineCombined sources1
    Modified residuei148PhosphotyrosineBy similarity1
    Modified residuei166N6-acetyllysine; alternateCombined sources1
    Modified residuei166N6-succinyllysine; alternateBy similarity1
    Cross-linki166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
    Modified residuei175PhosphotyrosineCombined sources1
    Modified residuei195PhosphothreonineCombined sources1
    Modified residuei249PhosphoserineBy similarity1
    Modified residuei266N6-acetyllysineCombined sources1
    Modified residuei270N6-acetyllysineBy similarity1
    Modified residuei305N6-acetyllysine1 Publication1
    Modified residuei322N6-acetyllysine; alternateBy similarity1
    Modified residuei322N6-succinyllysine; alternateBy similarity1
    Modified residuei4034-hydroxyproline1 Publication1
    Modified residuei4084-hydroxyproline1 Publication1
    Modified residuei433N6-acetyllysineCombined sources1
    Modified residuei475N6-acetyllysineBy similarity1
    Modified residuei498N6-succinyllysineBy similarity1

    Post-translational modificationi

    ISGylated.1 Publication
    Under hypoxia, hydroxylated by EGLN3.1 Publication
    Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.2 Publications
    FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.1 Publication

    Keywords - PTMi

    Acetylation, Hydroxylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiP14618.
    PaxDbiP14618.
    PeptideAtlasiP14618.
    PRIDEiP14618.
    TopDownProteomicsiP14618-1. [P14618-1]
    P14618-2. [P14618-2]

    2D gel databases

    DOSAC-COBS-2DPAGEP14618.
    OGPiP14618.
    REPRODUCTION-2DPAGEIPI00220644.
    IPI00479186.
    UCD-2DPAGEP14618.

    PTM databases

    iPTMnetiP14618.
    PhosphoSitePlusiP14618.
    SwissPalmiP14618.

    Expressioni

    Tissue specificityi

    Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells.1 Publication

    Gene expression databases

    BgeeiENSG00000067225.
    CleanExiHS_PKM2.
    ExpressionAtlasiP14618. baseline and differential.
    GenevisibleiP14618. HS.

    Organism-specific databases

    HPAiCAB019421.
    HPA029501.

    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 T3. Tetramer formation induces pyruvate kinase activity. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. Exists in a nearly inactive dimeric form in tumor cells and the dimeric form has less affinity for the substrate. Binding to certain oncoproteins such as HPV-16 E7 oncoprotein can trigger dimerization. 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. Interacts (isoform M2, but not isoform M1) with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation (PubMed:25263439).11 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Q9WMX24EBI-353408,EBI-710918From a different organism.
    ARAFP103982EBI-353408,EBI-365961
    ARRB1P494073EBI-353408,EBI-743313
    ARRB2P321214EBI-353408,EBI-714559
    DAPK1P533553EBI-353408,EBI-358616
    EGLN3Q9H6Z92EBI-4304679,EBI-1175354
    HIF1AQ166657EBI-4304679,EBI-447269
    HIST1H3DP684313EBI-4304679,EBI-79722
    HTTP428583EBI-353408,EBI-466029
    MAPK3P273613EBI-4304679,EBI-73995
    RAF1P040493EBI-353408,EBI-365996
    TINF2Q9BSI42EBI-353408,EBI-717399

    GO - Molecular functioni

    • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
    • MHC class II protein complex binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi111332. 177 interactors.
    DIPiDIP-31273N.
    IntActiP14618. 241 interactors.
    MINTiMINT-4998892.
    STRINGi9606.ENSP00000320171.

    Chemistry databases

    BindingDBiP14618.

    Structurei

    Secondary structure

    1531
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi15 – 17Combined sources3
    Helixi18 – 21Combined sources4
    Helixi26 – 31Combined sources6
    Beta strandi35 – 37Combined sources3
    Beta strandi45 – 50Combined sources6
    Turni53 – 55Combined sources3
    Helixi58 – 67Combined sources10
    Beta strandi71 – 75Combined sources5
    Helixi76 – 78Combined sources3
    Helixi81 – 96Combined sources16
    Turni97 – 100Combined sources4
    Turni102 – 104Combined sources3
    Beta strandi109 – 113Combined sources5
    Beta strandi119 – 121Combined sources3
    Beta strandi127 – 129Combined sources3
    Beta strandi132 – 134Combined sources3
    Beta strandi139 – 143Combined sources5
    Helixi146 – 148Combined sources3
    Beta strandi154 – 160Combined sources7
    Helixi164 – 167Combined sources4
    Beta strandi173 – 176Combined sources4
    Turni177 – 180Combined sources4
    Beta strandi181 – 188Combined sources8
    Beta strandi190 – 199Combined sources10
    Beta strandi201 – 203Combined sources3
    Beta strandi204 – 206Combined 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
    Beta strandi367 – 369Combined sources3
    Helixi371 – 387Combined sources17
    Helixi391 – 401Combined sources11
    Turni402 – 404Combined sources3
    Helixi408 – 422Combined sources15
    Beta strandi428 – 431Combined sources4
    Beta strandi433 – 435Combined sources3
    Helixi436 – 442Combined sources7
    Beta strandi450 – 455Combined sources6
    Helixi457 – 462Combined sources6
    Helixi463 – 465Combined sources3
    Beta strandi469 – 473Combined sources5
    Helixi482 – 499Combined sources18
    Beta strandi508 – 518Combined sources11
    Beta strandi522 – 529Combined sources8

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1T5AX-ray2.80A/B/C/D1-531[»]
    1ZJHX-ray2.20A3-531[»]
    3BJFX-ray2.03A/B/C/D14-531[»]
    3BJTX-ray2.50A/B/C/D2-531[»]
    3G2GX-ray2.00A/B/C/D1-531[»]
    3GQYX-ray1.85A/B/C/D1-531[»]
    3GR4X-ray1.60A/B/C/D1-531[»]
    3H6OX-ray2.00A/B/C/D1-531[»]
    3ME3X-ray1.95A/B/C/D1-531[»]
    3SRDX-ray2.90A/B/C/D1-531[»]
    3SRFX-ray2.84A/B/C/D/E/F/G/H1-531[»]
    3SRHX-ray2.60A/B/C/D1-531[»]
    3U2ZX-ray2.10A/B/C/D1-531[»]
    4B2DX-ray2.30A/B/C/D2-531[»]
    4FXFX-ray2.55A/B/C/D1-531[»]
    4FXJX-ray2.90A/B/C/D1-531[»]
    4G1NX-ray2.30A/B/C/D14-531[»]
    4JPGX-ray2.33A/B/C/D1-531[»]
    4QG6X-ray3.21A/B/C/D1-531[»]
    4QG8X-ray2.30A/B/C/D1-531[»]
    4QG9X-ray2.38A/B/C/D1-531[»]
    4QGCX-ray2.30A/B/C/D1-531[»]
    4RPPX-ray2.58A/B/C/D1-531[»]
    4WJ8X-ray2.87A/B/C/D1-531[»]
    4YJ5X-ray2.41A/B/C/D14-531[»]
    ProteinModelPortaliP14618.
    SMRiP14618.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14618.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni307 – 531Interaction with POU5F11 PublicationAdd BLAST225
    Regioni389 – 433Intersubunit contactAdd BLAST45
    Regioni432 – 437D-fructose 1,6-bisphosphate binding; part of allosteric siteCombined sources2 Publications6
    Regioni516 – 521D-fructose 1,6-bisphosphate binding; part of allosteric siteCombined sources2 Publications6

    Sequence similaritiesi

    Belongs to the pyruvate kinase family.Curated

    Phylogenomic databases

    eggNOGiKOG2323. Eukaryota.
    COG0469. LUCA.
    GeneTreeiENSGT00390000008859.
    HOGENOMiHOG000021559.
    HOVERGENiHBG000941.
    InParanoidiP14618.
    KOiK00873.
    OMAiKQHGGEH.
    PhylomeDBiP14618.
    TreeFamiTF300390.

    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 (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform M2 (identifier: P14618-1) [UniParc]FASTAAdd to basket
    Also known as: M2-PK, PKM2

    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
    MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT
    60 70 80 90 100
    IGPASRSVET LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRTATESFAS
    110 120 130 140 150
    DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
    160 170 180 190 200
    KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKQKGA DFLVTEVENG
    210 220 230 240 250
    GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKASD
    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 IAREAEAAIY HLQLFEELRR
    410 420 430 440 450
    LAPITSDPTE ATAVGAVEAS FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI
    460 470 480 490 500
    IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE AWAEDVDLRV NFAMNVGKAR
    510 520 530
    GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
    Length:531
    Mass (Da):57,937
    Last modified:January 23, 2007 - v4
    Checksum:iAA94D7818ED6BBAD
    GO
    Isoform M1 (identifier: P14618-2) [UniParc] [UniParc]FASTAAdd to basket
    Also known as: M1-PK, PKM1

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

    Show »
    Length:531
    Mass (Da):58,062
    Checksum:iAB9B5B2308D26B79
    GO
    Isoform 3 (identifier: P14618-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-82: MSKPHSEAGT...RLNFSHGTHE → MSPEAQPQRT...PGTLASSVPL

    Note: No experimental confirmation available.
    Show »
    Length:516
    Mass (Da):56,273
    Checksum:i23200C40C7C42045
    GO

    Sequence cautioni

    The sequence BAG57589 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti7E → Q in AAH12811 (PubMed:15489334).Curated1
    Sequence conflicti54A → T in BAG52542 (PubMed:14702039).Curated1
    Sequence conflicti103I → Y in AAA36672 (PubMed:2813362).Curated1
    Sequence conflicti132V → L in AAA36672 (PubMed:2813362).Curated1
    Sequence conflicti187Q → R in BAD96647 (Ref. 5) Curated1
    Sequence conflicti252H → R in BAD96647 (Ref. 5) Curated1
    Sequence conflicti339R → P in CAA39849 (PubMed:2040271).Curated1
    Sequence conflicti349A → V in BAG52542 (PubMed:14702039).Curated1
    Sequence conflicti379H → N in AAA36449 (PubMed:2854097).Curated1
    Sequence conflicti507D → H in AAH12811 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_033067204G → V.1 PublicationCorresponds to variant rs17853396dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0433701 – 82MSKPH…HGTHE → MSPEAQPQRTKGPQQPCRSP IVKPGLPSFRPSSCTQPWLT HSWSTCAAWTLIHHPSQPGT LASSVPL in isoform 3. 1 PublicationAdd BLAST82
    Alternative sequenceiVSP_011101389 – 433IYHLQ…IVLTK → MFHRKLFEELVRASSHSTDL MEAMAMGSVEASYKCLAAAL IVLTE in isoform M1. 1 PublicationAdd BLAST45

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M23725 mRNA. Translation: AAA36449.1.
    M26252 mRNA. Translation: AAA36672.1.
    X56494 Genomic DNA. Translation: CAA39849.1.
    AK092369 mRNA. Translation: BAG52542.1.
    AK222927 mRNA. Translation: BAD96647.1.
    AK294315 mRNA. Translation: BAG57589.1. Different initiation.
    AK300800 mRNA. Translation: BAG62458.1.
    AK312253 mRNA. Translation: BAG35185.1.
    AY352517 Genomic DNA. Translation: AAQ15274.1.
    AC020779 Genomic DNA. No translation available.
    CH471082 Genomic DNA. Translation: EAW77884.1.
    CH471082 Genomic DNA. Translation: EAW77888.1.
    BC000481 mRNA. Translation: AAH00481.3.
    BC007640 mRNA. Translation: AAH07640.1.
    BC007952 mRNA. Translation: AAH07952.3.
    BC012811 mRNA. Translation: AAH12811.3.
    BC035198 mRNA. Translation: AAH35198.1.
    AF025439 mRNA. Translation: AAC39559.1.
    CCDSiCCDS32284.1. [P14618-1]
    CCDS32285.1. [P14618-2]
    CCDS55972.1. [P14618-3]
    PIRiS30038.
    S64635.
    RefSeqiNP_001193725.1. NM_001206796.2.
    NP_001193726.1. NM_001206797.2.
    NP_001193727.1. NM_001206798.2. [P14618-3]
    NP_001193728.1. NM_001206799.1.
    NP_001303247.1. NM_001316318.1.
    NP_002645.3. NM_002654.5. [P14618-1]
    NP_872270.1. NM_182470.3. [P14618-2]
    NP_872271.1. NM_182471.3. [P14618-2]
    XP_005254502.1. XM_005254445.4. [P14618-1]
    XP_016877802.1. XM_017022313.1. [P14618-2]
    UniGeneiHs.534770.
    Hs.704299.

    Genome annotation databases

    EnsembliENST00000319622; ENSP00000320171; ENSG00000067225. [P14618-2]
    ENST00000335181; ENSP00000334983; ENSG00000067225. [P14618-1]
    ENST00000449901; ENSP00000403365; ENSG00000067225. [P14618-3]
    ENST00000565154; ENSP00000455901; ENSG00000067225. [P14618-2]
    ENST00000565184; ENSP00000455736; ENSG00000067225. [P14618-2]
    ENST00000568459; ENSP00000456970; ENSG00000067225. [P14618-2]
    GeneIDi5315.
    KEGGihsa:5315.
    UCSCiuc002atw.2. human. [P14618-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Wikipedia

    Pyruvate kinase entry

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M23725 mRNA. Translation: AAA36449.1.
    M26252 mRNA. Translation: AAA36672.1.
    X56494 Genomic DNA. Translation: CAA39849.1.
    AK092369 mRNA. Translation: BAG52542.1.
    AK222927 mRNA. Translation: BAD96647.1.
    AK294315 mRNA. Translation: BAG57589.1. Different initiation.
    AK300800 mRNA. Translation: BAG62458.1.
    AK312253 mRNA. Translation: BAG35185.1.
    AY352517 Genomic DNA. Translation: AAQ15274.1.
    AC020779 Genomic DNA. No translation available.
    CH471082 Genomic DNA. Translation: EAW77884.1.
    CH471082 Genomic DNA. Translation: EAW77888.1.
    BC000481 mRNA. Translation: AAH00481.3.
    BC007640 mRNA. Translation: AAH07640.1.
    BC007952 mRNA. Translation: AAH07952.3.
    BC012811 mRNA. Translation: AAH12811.3.
    BC035198 mRNA. Translation: AAH35198.1.
    AF025439 mRNA. Translation: AAC39559.1.
    CCDSiCCDS32284.1. [P14618-1]
    CCDS32285.1. [P14618-2]
    CCDS55972.1. [P14618-3]
    PIRiS30038.
    S64635.
    RefSeqiNP_001193725.1. NM_001206796.2.
    NP_001193726.1. NM_001206797.2.
    NP_001193727.1. NM_001206798.2. [P14618-3]
    NP_001193728.1. NM_001206799.1.
    NP_001303247.1. NM_001316318.1.
    NP_002645.3. NM_002654.5. [P14618-1]
    NP_872270.1. NM_182470.3. [P14618-2]
    NP_872271.1. NM_182471.3. [P14618-2]
    XP_005254502.1. XM_005254445.4. [P14618-1]
    XP_016877802.1. XM_017022313.1. [P14618-2]
    UniGeneiHs.534770.
    Hs.704299.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1T5AX-ray2.80A/B/C/D1-531[»]
    1ZJHX-ray2.20A3-531[»]
    3BJFX-ray2.03A/B/C/D14-531[»]
    3BJTX-ray2.50A/B/C/D2-531[»]
    3G2GX-ray2.00A/B/C/D1-531[»]
    3GQYX-ray1.85A/B/C/D1-531[»]
    3GR4X-ray1.60A/B/C/D1-531[»]
    3H6OX-ray2.00A/B/C/D1-531[»]
    3ME3X-ray1.95A/B/C/D1-531[»]
    3SRDX-ray2.90A/B/C/D1-531[»]
    3SRFX-ray2.84A/B/C/D/E/F/G/H1-531[»]
    3SRHX-ray2.60A/B/C/D1-531[»]
    3U2ZX-ray2.10A/B/C/D1-531[»]
    4B2DX-ray2.30A/B/C/D2-531[»]
    4FXFX-ray2.55A/B/C/D1-531[»]
    4FXJX-ray2.90A/B/C/D1-531[»]
    4G1NX-ray2.30A/B/C/D14-531[»]
    4JPGX-ray2.33A/B/C/D1-531[»]
    4QG6X-ray3.21A/B/C/D1-531[»]
    4QG8X-ray2.30A/B/C/D1-531[»]
    4QG9X-ray2.38A/B/C/D1-531[»]
    4QGCX-ray2.30A/B/C/D1-531[»]
    4RPPX-ray2.58A/B/C/D1-531[»]
    4WJ8X-ray2.87A/B/C/D1-531[»]
    4YJ5X-ray2.41A/B/C/D14-531[»]
    ProteinModelPortaliP14618.
    SMRiP14618.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi111332. 177 interactors.
    DIPiDIP-31273N.
    IntActiP14618. 241 interactors.
    MINTiMINT-4998892.
    STRINGi9606.ENSP00000320171.

    Chemistry databases

    BindingDBiP14618.
    ChEMBLiCHEMBL1075189.
    DrugBankiDB00119. Pyruvic acid.

    PTM databases

    iPTMnetiP14618.
    PhosphoSitePlusiP14618.
    SwissPalmiP14618.

    Polymorphism and mutation databases

    BioMutaiPKM.
    DMDMi20178296.

    2D gel databases

    DOSAC-COBS-2DPAGEP14618.
    OGPiP14618.
    REPRODUCTION-2DPAGEIPI00220644.
    IPI00479186.
    UCD-2DPAGEP14618.

    Proteomic databases

    EPDiP14618.
    PaxDbiP14618.
    PeptideAtlasiP14618.
    PRIDEiP14618.
    TopDownProteomicsiP14618-1. [P14618-1]
    P14618-2. [P14618-2]

    Protocols and materials databases

    DNASUi5315.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000319622; ENSP00000320171; ENSG00000067225. [P14618-2]
    ENST00000335181; ENSP00000334983; ENSG00000067225. [P14618-1]
    ENST00000449901; ENSP00000403365; ENSG00000067225. [P14618-3]
    ENST00000565154; ENSP00000455901; ENSG00000067225. [P14618-2]
    ENST00000565184; ENSP00000455736; ENSG00000067225. [P14618-2]
    ENST00000568459; ENSP00000456970; ENSG00000067225. [P14618-2]
    GeneIDi5315.
    KEGGihsa:5315.
    UCSCiuc002atw.2. human. [P14618-1]

    Organism-specific databases

    CTDi5315.
    DisGeNETi5315.
    GeneCardsiPKM.
    HGNCiHGNC:9021. PKM.
    HPAiCAB019421.
    HPA029501.
    MIMi179050. gene.
    neXtProtiNX_P14618.
    OpenTargetsiENSG00000067225.
    PharmGKBiPA33353.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2323. Eukaryota.
    COG0469. LUCA.
    GeneTreeiENSGT00390000008859.
    HOGENOMiHOG000021559.
    HOVERGENiHBG000941.
    InParanoidiP14618.
    KOiK00873.
    OMAiKQHGGEH.
    PhylomeDBiP14618.
    TreeFamiTF300390.

    Enzyme and pathway databases

    UniPathwayiUPA00109; UER00188.
    BioCyciMetaCyc:HS00906-MONOMER.
    ZFISH:HS00906-MONOMER.
    BRENDAi2.7.1.40. 2681.
    ReactomeiR-HSA-6798695. Neutrophil degranulation.
    R-HSA-70171. Glycolysis.
    SABIO-RKP14618.
    SIGNORiP14618.

    Miscellaneous databases

    EvolutionaryTraceiP14618.
    GeneWikiiPKM2.
    GenomeRNAii5315.
    PROiP14618.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000067225.
    CleanExiHS_PKM2.
    ExpressionAtlasiP14618. baseline and differential.
    GenevisibleiP14618. HS.

    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_HUMAN
    AccessioniPrimary (citable) accession number: P14618
    Secondary accession number(s): A6NFK3
    , B2R5N8, B3KRY0, B4DFX8, B4DUU6, P14786, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: January 23, 2007
    Last modified: November 30, 2016
    This is version 220 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    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. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. 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.