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P14618 (KPYM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 190. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PKM
Synonyms:OIP3, PK2, PK3, PKM2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 betwween 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. Ref.21 Ref.23 Ref.32

Catalytic activity

ATP + pyruvate = ADP + phosphoenolpyruvate. Ref.12 Ref.36

Cofactor

Magnesium.

Potassium.

Enzyme regulation

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. Ref.2 Ref.12 Ref.22 Ref.36 Ref.38 Ref.39

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.

Subunit structure

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. 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. Ref.2 Ref.12 Ref.16 Ref.22 Ref.23 Ref.32 Ref.33 Ref.36 Ref.39

Subcellular location

Cytoplasm. 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. Ref.21 Ref.22 Ref.23 Ref.32

Tissue specificity

Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells. Ref.23

Post-translational modification

ISGylated. Ref.17

Under hypoxia, hydroxylated by EGLN3.

Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy. Ref.11 Ref.34

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.

Sequence similarities

Belongs to the pyruvate kinase family.

Biophysicochemical properties

Kinetic parameters:

KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0) Ref.12 Ref.36

KM=0.17 mM for phosphoenolpyruvate (in the presence of 2 mM FBP, at 32 degrees Celsius, pH 8.0)

KM=0.34 mM for ADP (at 32 degrees Celsius, pH 8.0)

KM=0.24 mM for ADP (in the presence of 2 mM FBP, at 32 degrees Celsius, pH 8.0)

KM=0.13 mM for phosphoenolpyruvate (in the presence of 2 mM FBP, at 25 degrees Celsius)

KM=0.63 mM for ADP (in the presence of 2 mM FBP, at 25 degrees Celsius)

pH dependence:

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.

Sequence caution

The sequence BAG57589.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processGlycolysis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Potassium
Pyruvate
   Molecular functionKinase
Transferase
   PTMAcetylation
Hydroxylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

glycolysis

Traceable author statement. Source: Reactome

programmed cell death

Inferred from direct assay Ref.21. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcilium

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.22. Source: UniProtKB

cytosol

Non-traceable author statement Ref.2. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 11487543PubMed 12519789PubMed 21362503. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

nucleus

Inferred from direct assay Ref.21Ref.23. Source: UniProtKB

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MHC class II protein complex binding

Inferred from direct assay PubMed 20458337. Source: UniProt

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

potassium ion binding

Inferred from electronic annotation. Source: InterPro

pyruvate kinase activity

Traceable author statement Ref.4Ref.2Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform M2 (identifier: P14618-1)

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.
Isoform M1 (identifier: P14618-2)

Also known as: M1-PK; PKM1;

The sequence of this isoform differs from the canonical sequence as follows:
     389-433: IYHLQLFEEL...CSGAIIVLTK → MFHRKLFEEL...LAAALIVLTE
Isoform 3 (identifier: P14618-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-82: MSKPHSEAGT...RLNFSHGTHE → MSPEAQPQRT...PGTLASSVPL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11 Ref.12 Ref.13
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112088

Regions

Region307 – 531225Interaction with POU5F1
Region389 – 43345Intersubunit contact
Region432 – 4376D-fructose 1,6-bisphosphate binding; part of allosteric site
Region514 – 5218D-fructose 1,6-bisphosphate binding; part of allosteric site

Sites

Metal binding751Potassium By similarity
Metal binding771Potassium By similarity
Metal binding1131Potassium
Metal binding1141Potassium; via carbonyl oxygen By similarity
Metal binding2721Magnesium
Metal binding2961Magnesium
Binding site701Serine
Binding site731Substrate By similarity
Binding site1061Serine
Binding site2951Substrate; via amide nitrogen By similarity
Binding site2961Substrate; via amide nitrogen By similarity
Binding site3281Substrate By similarity
Binding site4641Serine
Binding site4821D-fructose 1,6-bisphosphate; part of allosteric site
Binding site4891D-fructose 1,6-bisphosphate; part of allosteric site
Site2701Transition state stabilizer
Site4331Crucial for phosphotyrosine binding

Amino acid modifications

Modified residue21N-acetylserine Ref.11 Ref.27
Modified residue371Phosphoserine Ref.19 Ref.20 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.35
Modified residue621N6-acetyllysine Ref.29
Modified residue661N6-succinyllysine By similarity
Modified residue891N6-acetyllysine Ref.29
Modified residue1051Phosphotyrosine Ref.18
Modified residue1481Phosphotyrosine By similarity
Modified residue1661N6-acetyllysine; alternate Ref.29
Modified residue1661N6-succinyllysine; alternate By similarity
Modified residue1751Phosphotyrosine Ref.28
Modified residue1951Phosphothreonine Ref.28
Modified residue2661N6-acetyllysine Ref.29
Modified residue2701N6-acetyllysine By similarity
Modified residue3051N6-acetyllysine Ref.34
Modified residue3221N6-acetyllysine; alternate By similarity
Modified residue3221N6-succinyllysine; alternate By similarity
Modified residue40314-hydroxyproline Ref.32
Modified residue40814-hydroxyproline Ref.32
Modified residue4331N6-acetyllysine Ref.29
Modified residue4751N6-acetyllysine By similarity
Modified residue4981N6-succinyllysine By similarity

Natural variations

Alternative sequence1 – 8282MSKPH…HGTHE → MSPEAQPQRTKGPQQPCRSP IVKPGLPSFRPSSCTQPWLT HSWSTCAAWTLIHHPSQPGT LASSVPL in isoform 3.
VSP_043370
Alternative sequence389 – 43345IYHLQ…IVLTK → MFHRKLFEELVRASSHSTDL MEAMAMGSVEASYKCLAAAL IVLTE in isoform M1.
VSP_011101
Natural variant2041G → V. Ref.10
Corresponds to variant rs17853396 [ dbSNP | Ensembl ].
VAR_033067

Experimental info

Mutagenesis4031P → A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-408. Ref.32
Mutagenesis4081P → A: Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-403. Ref.32
Mutagenesis4371S → Y: Unable to bind FBP but still activated by serine. Ref.39
Mutagenesis4641H → A: Abolishes serine binding and allosteric activation. Ref.39
Sequence conflict71E → Q in AAH12811. Ref.10
Sequence conflict541A → T in BAG52542. Ref.5
Sequence conflict1031I → Y in AAA36672. Ref.2
Sequence conflict1321V → L in AAA36672. Ref.2
Sequence conflict1871Q → R in BAD96647. Ref.6
Sequence conflict2521H → R in BAD96647. Ref.6
Sequence conflict3391R → P in CAA39849. Ref.4
Sequence conflict3491A → V in BAG52542. Ref.5
Sequence conflict3791H → N in AAA36449. Ref.1
Sequence conflict5071D → H in AAH12811. Ref.10

Secondary structure

........................................................................................................ 531
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform M2 (M2-PK) (PKM2) [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: AA94D7818ED6BBAD

FASTA53157,937
        10         20         30         40         50         60 
MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVET 

        70         80         90        100        110        120 
LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRTATESFAS DPILYRPVAV ALDTKGPEIR 

       130        140        150        160        170        180 
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL 

       190        200        210        220        230        240 
ISLQVKQKGA DFLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV 

       250        260        270        280        290        300 
FASFIRKASD VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE 

       310        320        330        340        350        360 
IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN AVLDGADCIM 

       370        380        390        400        410        420 
LSGETAKGDY PLEAVRMQHL IAREAEAAIY HLQLFEELRR LAPITSDPTE ATAVGAVEAS 

       430        440        450        460        470        480 
FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE 

       490        500        510        520        530 
AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P 

« Hide

Isoform M1 (M1-PK) (PKM1) [UniParc] [UniParc].

Checksum: AB9B5B2308D26B79
Show »

FASTA53158,062
Isoform 3 [UniParc].

Checksum: 23200C40C7C42045
Show »

FASTA51656,273

References

« Hide 'large scale' references
[1]"Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and expression in hepatoma."
Tani K., Yoshida M.C., Satoh H., Mitamura K., Noguchi T., Tanaka T., Fujii H., Miwa S.
Gene 73:509-516(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
Tissue: Liver.
[2]"Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase."
Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y.
Proc. Natl. Acad. Sci. U.S.A. 86:7861-7865(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2), PROTEIN SEQUENCE OF 70-98, SUBUNIT, ENZYME REGULATION.
[3]Erratum
Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y.
Proc. Natl. Acad. Sci. U.S.A. 87:1625-1625(1990)
[4]"Isolation and characterization of the human pyruvate kinase M gene."
Takenaka M., Noguchi T., Sadahiro S., Hirai H., Yamada K., Matsuda T., Imai E., Tanaka T.
Eur. J. Biochem. 198:101-106(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS M1 AND 3).
Tissue: Astrocyte and Fetal brain.
[6]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2).
Tissue: Kidney.
[7]NIEHS SNPs program
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2), VARIANT VAL-204.
Tissue: Kidney, Lung carcinoma, Ovary, Retina and Rhabdomyosarcoma.
[11]Bienvenut W.V.
Submitted (JUL-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-43; 57-73; 93-115; 126-135; 167-186; 231-246; 271-311; 401-422; 448-455 AND 490-498, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: B-cell lymphoma.
[12]"An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate."
Ashizawa K., McPhie P., Lin K.-H., Cheng S.-Y.
Biochemistry 30:7105-7111(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-18, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, INTERACTION WITH THYROID HORMONE.
[13]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-32.
Tissue: Platelet.
[14]Lubec G., Vishwanath V.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 74-89, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[15]"Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth."
Williams J.M., Chen G.-C., Zhu L., Rest R.F.
Mol. Microbiol. 27:171-186(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-531 (ISOFORM M2).
[16]"Interaction between HERC1 and M2-type pyruvate kinase."
Garcia-Gonzalo F.R., Cruz C., Munoz P., Mazurek S., Eigenbrodt E., Ventura F., Bartrons R., Rosa J.L.
FEBS Lett. 539:78-84(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HERC1.
[17]"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells."
Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.
Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[18]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death."
Stetak A., Veress R., Ovadi J., Csermely P., Keri G., Ullrich A.
Cancer Res. 67:1602-1608(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[22]"Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein."
Shimada N., Shinagawa T., Ishii S.
Genes Cells 13:245-254(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PML, ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION.
[23]"Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription."
Lee J., Kim H.K., Han Y.-M., Kim J.
Int. J. Biochem. Cell Biol. 40:1043-1054(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH POU5F1, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[24]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[25]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; TYR-175 AND THR-195, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[29]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-89; LYS-166; LYS-266 AND LYS-433, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1."
Luo W., Hu H., Chang R., Zhong J., Knabel M., O'Meally R., Cole R.N., Pandey A., Semenza G.L.
Cell 145:732-744(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EGLN3 AND HIF1A, SUBCELLULAR LOCATION, INDUCTION, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, HYDROXYLATION AT PRO-403 AND PRO-408, MUTAGENESIS OF PRO-403 AND PRO-408.
[33]"The oxygen sensor PHD3 limits glycolysis under hypoxia via direct binding to pyruvate kinase."
Chen N., Rinner O., Czernik D., Nytko K.J., Zheng D., Stiehl D.P., Zamboni N., Gstaiger M., Frei C.
Cell Res. 21:983-986(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EGLN3.
[34]"Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth."
Lv L., Li D., Zhao D., Lin R., Chu Y., Zhang H., Zha Z., Liu Y., Li Z., Xu Y., Wang G., Huang Y., Xiong Y., Guan K.L., Lei Q.Y.
Mol. Cell 42:719-730(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-305.
[35]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis."
Dombrauckas J.D., Santarsiero B.D., Mesecar A.D.
Biochemistry 44:9417-9429(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF ISOFORM M2 IN COMPLEX WITH OXALATE AND FBP, CATALYTIC ACTIVITY, SUBUNIT, ENZYME MECHANISM, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[37]"Structure of human muscle pyruvate kinase (PKM2)."
Structural genomics consortium (SGC)
Submitted (MAY-2005) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[38]"Pyruvate kinase M2 is a phosphotyrosine-binding protein."
Christofk H.R., Vander Heiden M.G., Wu N., Asara J.M., Cantley L.C.
Nature 452:181-186(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 14-531 ALONE AND IN COMPLEX WITH FBP, ENZYME REGULATION.
[39]"Serine is a natural ligand and allosteric activator of pyruvate kinase M2."
Chaneton B., Hillmann P., Zheng L., Martin A.C., Maddocks O.D., Chokkathukalam A., Coyle J.E., Jankevics A., Holding F.P., Vousden K.H., Frezza C., O'Reilly M., Gottlieb E.
Nature 491:458-462(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-531, ENZYME REGULATION BY SERINE, MAGNESIUM-BINDING SITES, SUBUNIT, MUTAGENESIS OF SER-437 AND HIS-464.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS30038.
S64635.
RefSeqNP_001193725.1. NM_001206796.1.
NP_001193726.1. NM_001206797.1.
NP_001193727.1. NM_001206798.1.
NP_001193728.1. NM_001206799.1.
NP_002645.3. NM_002654.4.
NP_872270.1. NM_182470.2.
NP_872271.1. NM_182471.2.
XP_005254502.1. XM_005254445.2.
UniGeneHs.534770.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T5AX-ray2.80A/B/C/D1-531[»]
1ZJHX-ray2.20A3-530[»]
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[»]
ProteinModelPortalP14618.
SMRP14618. Positions 13-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111332. 109 interactions.
DIPDIP-31273N.
IntActP14618. 81 interactions.
MINTMINT-4998892.

Chemistry

BindingDBP14618.
ChEMBLCHEMBL1075189.
DrugBankDB00119. Pyruvic acid.

PTM databases

PhosphoSiteP14618.

Polymorphism databases

DMDM20178296.

2D gel databases

DOSAC-COBS-2DPAGEP14618.
OGPP14618.
REPRODUCTION-2DPAGEIPI00220644.
IPI00479186.
UCD-2DPAGEP14618.

Proteomic databases

PaxDbP14618.
PRIDEP14618.

Protocols and materials databases

DNASU5315.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000319622; ENSP00000320171; ENSG00000067225. [P14618-2]
ENST00000335181; ENSP00000334983; ENSG00000067225. [P14618-1]
ENST00000389093; ENSP00000373745; ENSG00000067225. [P14618-2]
ENST00000449901; ENSP00000403365; ENSG00000067225. [P14618-3]
ENST00000565154; ENSP00000455901; ENSG00000067225. [P14618-2]
ENST00000565184; ENSP00000455736; ENSG00000067225. [P14618-2]
ENST00000568459; ENSP00000456970; ENSG00000067225. [P14618-2]
GeneID5315.
KEGGhsa:5315.
UCSCuc002atv.2. human. [P14618-2]
uc002aty.2. human. [P14618-1]
uc010ukj.2. human. [P14618-3]

Organism-specific databases

CTD5315.
GeneCardsGC15M072492.
HGNCHGNC:9021. PKM.
HPACAB019421.
HPA029501.
MIM179050. gene.
neXtProtNX_P14618.
PharmGKBPA33353.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0469.
HOGENOMHOG000021559.
HOVERGENHBG000941.
InParanoidP14618.
KOK00873.
OMAHGTRIAN.
OrthoDBEOG78M01Q.
PhylomeDBP14618.
TreeFamTF300390.

Enzyme and pathway databases

BioCycMetaCyc:HS00906-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP14618.
UniPathwayUPA00109; UER00188.

Gene expression databases

ArrayExpressP14618.
BgeeP14618.
CleanExHS_PKM2.
GenevestigatorP14618.

Family and domain databases

Gene3D2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProIPR001697. 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]
PANTHERPTHR11817. PTHR11817. 1 hit.
PfamPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSPR01050. PYRUVTKNASE.
SUPFAMSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsTIGR01064. pyruv_kin. 1 hit.
PROSITEPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPKM2. human.
EvolutionaryTraceP14618.
GeneWikiPKM2.
GenomeRNAi5315.
NextBio20554.
PROP14618.
SOURCESearch...

Entry information

Entry nameKPYM_HUMAN
AccessionPrimary (citable) accession number: P14618
Secondary accession number(s): A6NFK3 expand/collapse secondary AC list , B2R5N8, B3KRY0, B4DFX8, B4DUU6, P14786, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 190 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM