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P11980

- KPYM_RAT

UniProt

P11980 - KPYM_RAT

Protein

Pyruvate kinase PKM

Gene

Pkm

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    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

    Magnesium.
    Potassium.

    Enzyme regulationi

    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 By similarity.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei70 – 701SerineBy similarity
    Binding sitei73 – 731SubstrateBy similarity
    Metal bindingi75 – 751PotassiumBy similarity
    Metal bindingi77 – 771PotassiumBy similarity
    Binding sitei106 – 1061SerineBy similarity
    Metal bindingi113 – 1131PotassiumBy similarity
    Metal bindingi114 – 1141Potassium; via carbonyl oxygenBy similarity
    Sitei270 – 2701Transition state stabilizerBy similarity
    Metal bindingi272 – 2721MagnesiumBy similarity
    Binding sitei295 – 2951Substrate; via amide nitrogenBy similarity
    Metal bindingi296 – 2961MagnesiumBy similarity
    Binding sitei296 – 2961Substrate; via amide nitrogenBy similarity
    Binding sitei328 – 3281SubstrateBy similarity
    Binding sitei464 – 4641SerineBy similarity
    Binding sitei482 – 4821D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity
    Binding sitei489 – 4891D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity

    GO - Molecular functioni

    1. ADP binding Source: RGD
    2. ATP binding Source: UniProtKB-KW
    3. magnesium ion binding Source: InterPro
    4. potassium ion binding Source: InterPro
    5. protein binding Source: RGD
    6. pyruvate kinase activity Source: RGD

    GO - Biological processi

    1. ATP biosynthetic process Source: RGD
    2. glucose metabolic process Source: RGD
    3. glycolytic process Source: RGD
    4. liver development Source: RGD
    5. organ regeneration Source: RGD
    6. pyruvate biosynthetic process Source: RGD
    7. response to gravity Source: RGD
    8. response to hypoxia Source: RGD
    9. response to insulin Source: RGD
    10. response to muscle inactivity Source: RGD
    11. response to nutrient Source: RGD
    12. response to organic substance Source: RGD
    13. skeletal muscle tissue regeneration Source: RGD

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Glycolysis

    Keywords - Ligandi

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

    Enzyme and pathway databases

    SABIO-RKP11980.
    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, Pykm
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 8

    Organism-specific databases

    RGDi3337. Pkm.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 531530Pyruvate kinase PKMPRO_0000112092Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei37 – 371PhosphoserineBy similarity
    Modified residuei62 – 621N6-acetyllysineBy similarity
    Modified residuei66 – 661N6-succinyllysineBy similarity
    Modified residuei89 – 891N6-acetyllysineBy similarity
    Modified residuei105 – 1051PhosphotyrosineBy similarity
    Modified residuei148 – 1481PhosphotyrosineBy similarity
    Modified residuei166 – 1661N6-acetyllysine; alternateBy similarity
    Modified residuei166 – 1661N6-succinyllysine; alternateBy similarity
    Modified residuei175 – 1751PhosphotyrosineBy similarity
    Modified residuei195 – 1951PhosphothreonineBy similarity
    Modified residuei266 – 2661N6-acetyllysineBy similarity
    Modified residuei270 – 2701N6-acetyllysineBy similarity
    Modified residuei305 – 3051N6-acetyllysineBy similarity
    Modified residuei322 – 3221N6-acetyllysine; alternateBy similarity
    Modified residuei322 – 3221N6-succinyllysine; alternateBy similarity
    Modified residuei408 – 40814-hydroxyprolineBy similarity
    Modified residuei475 – 4751N6-acetyllysineBy similarity
    Modified residuei498 – 4981N6-succinyllysineBy similarity

    Post-translational modificationi

    ISGylated.By similarity
    Under hypoxia, hydroxylated by EGLN3.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, Hydroxylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP11980.
    PRIDEiP11980.

    2D gel databases

    World-2DPAGE0004:P11980.

    PTM databases

    PhosphoSiteiP11980.

    Expressioni

    Gene expression databases

    GenevestigatoriP11980.

    Interactioni

    Subunit structurei

    Monomer and homotetramer. Exists as a monomer in the absence of FBP, and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds T3. Tetramer formation induces pyruvate kinase activity. Interacts with HERC1 formation induces pyruvate kinase activity. Interacts with HERC1, POU5F1 and PML. Interacts 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.By similarity

    Protein-protein interaction databases

    BioGridi247659. 3 interactions.
    IntActiP11980. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP11980.
    SMRiP11980. Positions 11-531.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni307 – 531225Interaction with POU5F1By similarityAdd
    BLAST
    Regioni389 – 43345Intersubunit contactAdd
    BLAST
    Regioni432 – 4376D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity
    Regioni514 – 5218D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity

    Sequence similaritiesi

    Belongs to the pyruvate kinase family.Curated

    Phylogenomic databases

    eggNOGiCOG0469.
    GeneTreeiENSGT00390000008859.
    HOGENOMiHOG000021559.
    HOVERGENiHBG000941.
    InParanoidiP11980.
    KOiK00873.
    OMAiYAAPGDQ.
    OrthoDBiEOG78M01Q.
    PhylomeDBiP11980.
    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 (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. Align

    Isoform M1 (identifier: P11980-1) [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

    MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT    50
    IGPASRSVEM LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS 100
    DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME 150
    KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKEKGA DYLVTEVENG 200
    GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKAAD 250
    VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE 300
    IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN 350
    AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAVF HRLLFEELAR 400
    ASSQSTDPLE AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI 450
    IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD AWAEDVDLRV NLAMNVGKAR 500
    GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P 531
    Length:531
    Mass (Da):57,818
    Last modified:January 23, 2007 - v3
    Checksum:iF0B133FDDD5991A9
    GO
    Isoform M2 (identifier: P11980-2) [UniParc] [UniParc]FASTAAdd to Basket

    Also known as: PKM2

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

    Show »
    Length:531
    Mass (Da):57,781
    Checksum:i321D9EB3500272DA
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei389 – 43345VFHRL…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2. CuratedVSP_011107Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    PIRiA26186.
    B26186.
    RefSeqiNP_445749.1. NM_053297.2. [P11980-1]
    UniGeneiRn.1556.

    Genome annotation databases

    EnsembliENSRNOT00000015332; ENSRNOP00000015331; ENSRNOG00000011329. [P11980-2]
    GeneIDi25630.
    KEGGirno:25630.
    UCSCiRGD:3337. rat. [P11980-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 ]
    UniGenei Rn.1556.

    3D structure databases

    ProteinModelPortali P11980.
    SMRi P11980. Positions 11-531.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247659. 3 interactions.
    IntActi P11980. 2 interactions.

    Chemistry

    BindingDBi P11980.
    ChEMBLi CHEMBL4994.

    PTM databases

    PhosphoSitei P11980.

    2D gel databases

    World-2DPAGE 0004:P11980.

    Proteomic databases

    PaxDbi P11980.
    PRIDEi P11980.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000015332 ; ENSRNOP00000015331 ; ENSRNOG00000011329 . [P11980-2 ]
    GeneIDi 25630.
    KEGGi rno:25630.
    UCSCi RGD:3337. rat. [P11980-1 ]

    Organism-specific databases

    CTDi 5315.
    RGDi 3337. Pkm.

    Phylogenomic databases

    eggNOGi COG0469.
    GeneTreei ENSGT00390000008859.
    HOGENOMi HOG000021559.
    HOVERGENi HBG000941.
    InParanoidi P11980.
    KOi K00873.
    OMAi YAAPGDQ.
    OrthoDBi EOG78M01Q.
    PhylomeDBi P11980.
    TreeFami TF300390.

    Enzyme and pathway databases

    UniPathwayi UPA00109 ; UER00188 .
    SABIO-RK P11980.

    Miscellaneous databases

    NextBioi 607431.

    Gene expression databases

    Genevestigatori P11980.

    Family and domain databases

    Gene3Di 2.40.33.10. 1 hit.
    3.20.20.60. 2 hits.
    3.40.1380.20. 1 hit.
    InterProi IPR001697. 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 ]
    PANTHERi PTHR11817. PTHR11817. 1 hit.
    Pfami PF00224. PK. 1 hit.
    PF02887. PK_C. 1 hit.
    [Graphical view ]
    PRINTSi PR01050. PYRUVTKNASE.
    SUPFAMi SSF50800. SSF50800. 1 hit.
    SSF51621. SSF51621. 2 hits.
    SSF52935. SSF52935. 1 hit.
    TIGRFAMsi TIGR01064. pyruv_kin. 1 hit.
    PROSITEi PS00110. PYRUVATE_KINASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing."
      Noguchi T., Inoue H., Tanaka T.
      J. Biol. Chem. 261:13807-13812(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS M1 AND M2).
    2. "Rat pyruvate kinase M gene: its complete structure and characterization of the 5'-flanking region."
      Takenaka M., Noguchi T., Inoue H., Yamada K., Matsuda T., Tanaka T.
      J. Biol. Chem. 264:2363-2367(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS M1 AND M2), SEQUENCE REVISION.
    3. "The nucleotide sequence of a full length cDNA encoding rat pituitary pyruvate kinase."
      Parkinson C., Kato H., Cheng S.
      Nucleic Acids Res. 17:7106-7106(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1).
      Tissue: Pituitary.
    4. Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.
      Submitted (JUL-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 33-56; 74-89; 93-115; 174-186; 208-246; 279-294; 343-376; 393-400; 423-436; 476-498 AND 505-526, PROTEIN SEQUENCE OF 384-399 (ISOFORM M2), IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: Sprague-Dawley.
      Tissue: Brain, Hippocampus and Spinal cord.

    Entry informationi

    Entry nameiKPYM_RAT
    AccessioniPrimary (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: October 1, 2014
    This is version 140 of the entry and version 3 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

    Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3