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P11979

- KPYM_FELCA

UniProt

P11979 - KPYM_FELCA

Protein

Pyruvate kinase PKM

Gene

PKM

Organism
Felis catus (Cat) (Felis silvestris catus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 2 (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. ATP binding Source: UniProtKB-KW
    2. magnesium ion binding Source: InterPro
    3. potassium ion binding Source: InterPro
    4. pyruvate kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. glycolytic process Source: UniProtKB-UniPathway

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Glycolysis

    Keywords - Ligandi

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

    Enzyme and pathway databases

    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
    OrganismiFelis catus (Cat) (Felis silvestris catus)
    Taxonomic identifieri9685 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraFeliformiaFelidaeFelinaeFelis
    ProteomesiUP000011712: Unplaced

    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 – 11Removed1 Publication
    Chaini2 – 531530Pyruvate kinase PKMPRO_0000112087Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    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 residuei475 – 4751N6-acetyllysineBy similarity
    Modified residuei498 – 4981N6-succinyllysineBy similarity

    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, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP11979.

    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 POU5F1 and PML By similarity.By similarity

    Protein-protein interaction databases

    STRINGi9685.ENSFCAP00000000606.

    Structurei

    Secondary structure

    1
    531
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi18 – 214
    Helixi26 – 316
    Beta strandi45 – 506
    Turni53 – 553
    Helixi58 – 669
    Beta strandi69 – 757
    Helixi81 – 9616
    Turni97 – 1004
    Turni102 – 1043
    Beta strandi109 – 1135
    Beta strandi119 – 1213
    Beta strandi139 – 1435
    Beta strandi148 – 1514
    Beta strandi154 – 1607
    Helixi164 – 1674
    Beta strandi173 – 1764
    Turni177 – 1804
    Beta strandi181 – 1888
    Beta strandi190 – 19910
    Beta strandi208 – 2103
    Helixi223 – 23412
    Beta strandi238 – 2436
    Helixi248 – 25811
    Turni259 – 2646
    Beta strandi265 – 2717
    Helixi275 – 2784
    Helixi280 – 2867
    Beta strandi287 – 2937
    Helixi294 – 3007
    Turni303 – 3053
    Helixi306 – 32015
    Beta strandi324 – 3318
    Helixi332 – 3354
    Helixi342 – 35413
    Beta strandi357 – 3626
    Helixi363 – 3664
    Helixi371 – 38717
    Helixi391 – 40212
    Helixi408 – 42316
    Beta strandi428 – 4314
    Beta strandi433 – 4353
    Helixi436 – 4438
    Beta strandi450 – 4556
    Helixi457 – 4626
    Helixi463 – 4653
    Beta strandi469 – 4735
    Helixi482 – 49918
    Beta strandi508 – 5136
    Beta strandi524 – 5296

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1PKMX-ray2.60A2-531[»]
    ProteinModelPortaliP11979.
    SMRiP11979. Positions 13-531.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11979.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni307 – 531225Interaction with POU5F1By similarityAdd
    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.
    HOGENOMiHOG000021559.
    HOVERGENiHBG000941.
    OrthoDBiEOG78M01Q.
    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: P11979-1) [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

    MSKPHSDVGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT    50
    IGPASRSVEI LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS 100
    DPIRYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME 150
    KCDENVLWLD YKNICKVVEV GSKVYVDDGL ISLLVKEKGA DFLVTEVENG 200
    GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKASD 250
    VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE 300
    IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN 350
    AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELVR 400
    GSSHSTDLME AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI 450
    IAVTRNHQTA RQAHLYRGIF PVVCKDPVQE AWAEDVDLRV NLAMNVGKAR 500
    GFFKHGDVVI VLTGWRPGSG FTNTMRVVPV P 531
    Length:531
    Mass (Da):58,046
    Last modified:January 23, 2007 - v2
    Checksum:i302475E32D6109A8
    GO
    Isoform M2 (identifier: P11979-2)

    Also known as: PKM2

    Sequence is not available
    Length:
    Mass (Da):

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti209 – 2091V → A AA sequence 1 PublicationCurated
    Sequence conflicti226 – 2272IQ → FE AA sequence 1 PublicationCurated
    Sequence conflicti232 – 2321G → Q AA sequence 1 PublicationCurated
    Sequence conflicti235 – 2351Q → R AA sequence 1 PublicationCurated

    Sequence databases

    PIRiA25091.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    PIRi A25091.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PKM X-ray 2.60 A 2-531 [» ]
    ProteinModelPortali P11979.
    SMRi P11979. Positions 13-531.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9685.ENSFCAP00000000606.

    Proteomic databases

    PRIDEi P11979.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    eggNOGi COG0469.
    HOGENOMi HOG000021559.
    HOVERGENi HBG000941.
    OrthoDBi EOG78M01Q.
    TreeFami TF300390.

    Enzyme and pathway databases

    UniPathwayi UPA00109 ; UER00188 .

    Miscellaneous databases

    EvolutionaryTracei P11979.

    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 structure of cat muscle pyruvate kinase."
      Muirhead H., Clayden D.A., Barford D., Lorimer C.G., Fothergill-Gilmore L.A., Schiltz E., Schmitt W.
      EMBO J. 5:475-481(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-531, ACETYLATION AT SER-2.
    2. "Hydroxylamine cleavage of cat skeletal-muscle pyruvate kinase: separation of the fragments and N-terminal sequence analysis."
      McAleese S.M., Hoar C.G., Dunbar B., Fothergill-Gilmore L.A.
      Biochem. Soc. Trans. 10:444-445(1982)
      Cited for: PROTEIN SEQUENCE OF 200-236.
    3. "A comparison of the structure and activity of cat and trout muscle pyruvate kinases."
      Harkins R.N., Nocton J.C., Russell M.P., Fothergill-Gilmore L.A., Muirhead H.
      Eur. J. Biochem. 136:341-346(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 314-330.
    4. "Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 A."
      Stuart D.I., Levine M., Muirhead H., Stammers D.K.
      J. Mol. Biol. 134:109-142(1979) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
    5. "Three-dimensional structure of cat muscle pyruvate kinase at 3.1-A resolution."
      Stammers D.K., Muirhead H.
      J. Mol. Biol. 112:309-316(1977) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
    6. "Three-dimensional structure of cat muscle pyruvate kinase at 6-A resolution."
      Stammers D.K., Muirhead H.
      J. Mol. Biol. 95:213-225(1975) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (6.0 ANGSTROMS).
    7. "Refined three-dimensional structure of cat-muscle (M1) pyruvate kinase at a resolution of 2.6 A."
      Allen S.C., Muirhead H.
      Acta Crystallogr. D 52:499-504(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).

    Entry informationi

    Entry nameiKPYM_FELCA
    AccessioniPrimary (citable) accession number: P11979
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 138 of the entry and version 2 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

    External Data

    Dasty 3