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P11980

- KPYM_RAT

UniProt

P11980 - KPYM_RAT

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Protein
Pyruvate kinase PKM
Gene
Pkm, Pkm2, Pykm
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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

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.

Pathwayi

Sites

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

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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 531530Pyruvate kinase PKM
PRO_0000112092Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371Phosphoserine By similarity
Modified residuei62 – 621N6-acetyllysine By similarity
Modified residuei66 – 661N6-succinyllysine By similarity
Modified residuei89 – 891N6-acetyllysine By similarity
Modified residuei105 – 1051Phosphotyrosine By similarity
Modified residuei148 – 1481Phosphotyrosine By similarity
Modified residuei166 – 1661N6-acetyllysine; alternate By similarity
Modified residuei166 – 1661N6-succinyllysine; alternate By similarity
Modified residuei175 – 1751Phosphotyrosine By similarity
Modified residuei195 – 1951Phosphothreonine By similarity
Modified residuei266 – 2661N6-acetyllysine By similarity
Modified residuei270 – 2701N6-acetyllysine By similarity
Modified residuei305 – 3051N6-acetyllysine By similarity
Modified residuei322 – 3221N6-acetyllysine; alternate By similarity
Modified residuei322 – 3221N6-succinyllysine; alternate By similarity
Modified residuei408 – 40814-hydroxyproline By similarity
Modified residuei475 – 4751N6-acetyllysine By similarity
Modified residuei498 – 4981N6-succinyllysine By 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.

Protein-protein interaction databases

BioGridi247659. 3 interactions.
IntActiP11980. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliP11980.
SMRiP11980. Positions 11-531.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni307 – 531225Interaction with POU5F1 By similarity
Add
BLAST
Regioni389 – 43345Intersubunit contact
Add
BLAST
Regioni432 – 4376D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity
Regioni514 – 5218D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity

Sequence similaritiesi

Belongs to the pyruvate kinase family.

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.
VSP_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: June 11, 2014
This is version 139 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

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