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P11974

- KPYM_RABIT

UniProt

P11974 - KPYM_RABIT

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Protein

Pyruvate kinase PKM

Gene

PKM

Organism
Oryctolagus cuniculus (Rabbit)
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).By similarity

Catalytic activityi

ATP + pyruvate = ADP + phosphoenolpyruvate.

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 (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
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-RKP11974.
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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
ProteomesiUP000001811: Unplaced

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 531530Pyruvate kinase PKMPRO_0000112091Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
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

PRIDEiP11974.

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, EGLN3 (isoform M2), HF1A, POU5F1 and PML (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CKMP005632EBI-7133357,EBI-2750756

Protein-protein interaction databases

DIPiDIP-47514N.
IntActiP11974. 1 interaction.
MINTiMINT-6824949.

Structurei

Secondary structure

1
531
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi18 – 214Combined sources
Helixi26 – 316Combined sources
Beta strandi45 – 506Combined sources
Turni53 – 553Combined sources
Helixi58 – 6710Combined sources
Beta strandi71 – 755Combined sources
Helixi81 – 9616Combined sources
Turni97 – 1004Combined sources
Turni102 – 1043Combined sources
Beta strandi109 – 1135Combined sources
Beta strandi119 – 1213Combined sources
Beta strandi126 – 1283Combined sources
Beta strandi130 – 1345Combined sources
Beta strandi139 – 1435Combined sources
Helixi146 – 1483Combined sources
Beta strandi154 – 1607Combined sources
Helixi164 – 1674Combined sources
Beta strandi173 – 1764Combined sources
Turni177 – 1804Combined sources
Beta strandi181 – 1899Combined sources
Beta strandi192 – 1998Combined sources
Beta strandi201 – 2033Combined sources
Beta strandi208 – 2103Combined sources
Beta strandi212 – 2143Combined sources
Helixi223 – 23412Combined sources
Beta strandi238 – 2425Combined sources
Helixi248 – 25811Combined sources
Turni259 – 2646Combined sources
Beta strandi265 – 2717Combined sources
Helixi274 – 2785Combined sources
Helixi280 – 2867Combined sources
Beta strandi287 – 2937Combined sources
Helixi294 – 3007Combined sources
Helixi303 – 3053Combined sources
Helixi306 – 32015Combined sources
Beta strandi324 – 3296Combined sources
Helixi332 – 3354Combined sources
Beta strandi337 – 3393Combined sources
Helixi342 – 35413Combined sources
Beta strandi357 – 3626Combined sources
Helixi363 – 3664Combined sources
Helixi371 – 38717Combined sources
Helixi391 – 40111Combined sources
Turni402 – 4043Combined sources
Helixi408 – 42316Combined sources
Beta strandi428 – 4314Combined sources
Beta strandi433 – 4353Combined sources
Helixi436 – 4438Combined sources
Beta strandi450 – 4556Combined sources
Helixi457 – 4626Combined sources
Helixi463 – 4653Combined sources
Beta strandi469 – 4735Combined sources
Helixi482 – 49918Combined sources
Beta strandi508 – 5136Combined sources
Beta strandi515 – 5184Combined sources
Beta strandi524 – 5296Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A49X-ray2.10A/B/C/D/E/F/G/H2-531[»]
1A5UX-ray2.35A/B/C/D/E/F/G/H2-531[»]
1AQFX-ray2.70A/B/C/D/E/F/G/H2-531[»]
1F3WX-ray3.00A/B/C/D/E/F/G/H2-531[»]
1F3XX-ray2.80A/B/C/D/E/F/G/H2-531[»]
1PKNX-ray2.90A2-531[»]
2G50X-ray1.65A/B/C/D/E/F/G/H2-531[»]
3N25X-ray2.41A/B/C/D/E/F/G/H1-531[»]
ProteinModelPortaliP11974.
SMRiP11974. Positions 13-531.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11974.

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.
InParanoidiP11974.

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: P11974-1) [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

        10         20         30         40         50
MSKSHSEAGS AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT
60 70 80 90 100
IGPASRSVET LKEMIKSGMN VARMNFSHGT HEYHAETIKN VRTATESFAS
110 120 130 140 150
DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENILWLD YKNICKVVDV GSKVYVDDGL ISLQVKQKGP DFLVTEVENG
210 220 230 240 250
GFLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKAAD
260 270 280 290 300
VHEVRKILGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
310 320 330 340 350
IPAEKVFLAQ KMIIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN
360 370 380 390 400
AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELAR
410 420 430 440 450
SSSHSTDLME AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNHQTA RQAHLYRGIF PVVCKDPVQE AWAEDVDLRV NLAMNVGKAR
510 520 530
GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
Length:531
Mass (Da):58,048
Last modified:January 23, 2007 - v4
Checksum:iAC0AFB579FC505E6
GO
Isoform M2 (identifier: P11974-2) [UniParc] [UniParc]FASTAAdd to Basket

Also known as: PKM2

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

Show »
Length:531
Mass (Da):57,905
Checksum:i5BCA6BC40C2FCA2D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti401 – 4011S → A in AAC48536. (PubMed:8626426)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei389 – 43345MFHRK…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2. 1 PublicationVSP_011106Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09028 mRNA. Translation: AAB61963.1.
U44751 mRNA. Translation: AAC48536.1.
AF032389 mRNA. Translation: AAB86587.1.
PIRiA28506.
A54113.
RefSeqiNP_001182573.1. NM_001195644.1.
NP_001182574.1. NM_001195645.1. [P11974-2]
UniGeneiOcu.2156.

Genome annotation databases

GeneIDi100008676.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Worthington enzyme manual

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09028 mRNA. Translation: AAB61963.1 .
U44751 mRNA. Translation: AAC48536.1 .
AF032389 mRNA. Translation: AAB86587.1 .
PIRi A28506.
A54113.
RefSeqi NP_001182573.1. NM_001195644.1.
NP_001182574.1. NM_001195645.1. [P11974-2 ]
UniGenei Ocu.2156.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A49 X-ray 2.10 A/B/C/D/E/F/G/H 2-531 [» ]
1A5U X-ray 2.35 A/B/C/D/E/F/G/H 2-531 [» ]
1AQF X-ray 2.70 A/B/C/D/E/F/G/H 2-531 [» ]
1F3W X-ray 3.00 A/B/C/D/E/F/G/H 2-531 [» ]
1F3X X-ray 2.80 A/B/C/D/E/F/G/H 2-531 [» ]
1PKN X-ray 2.90 A 2-531 [» ]
2G50 X-ray 1.65 A/B/C/D/E/F/G/H 2-531 [» ]
3N25 X-ray 2.41 A/B/C/D/E/F/G/H 1-531 [» ]
ProteinModelPortali P11974.
SMRi P11974. Positions 13-531.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-47514N.
IntActi P11974. 1 interaction.
MINTi MINT-6824949.

Chemistry

ChEMBLi CHEMBL5637.

Proteomic databases

PRIDEi P11974.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100008676.

Organism-specific databases

CTDi 5315.

Phylogenomic databases

eggNOGi COG0469.
HOGENOMi HOG000021559.
HOVERGENi HBG000941.
InParanoidi P11974.

Enzyme and pathway databases

UniPathwayi UPA00109 ; UER00188 .
SABIO-RK P11974.

Miscellaneous databases

EvolutionaryTracei P11974.

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. "Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate."
    Larsen T.M., Laughlin L.T., Holden H.M., Rayment I., Reed G.H.
    Biochemistry 33:6301-6309(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1), X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH MANGANESE AND PAOTASSIUM IONS AND PYRUVATE.
    Tissue: Skeletal muscle.
  2. Laughlin L.T.
    Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO 234-235.
  3. "Effects of conserved residues on the regulation of rabbit muscle pyruvate kinase."
    Cheng X., Friesen R.H.E., Lee J.C.
    J. Biol. Chem. 271:6313-6321(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1).
  4. "Interfacial communications in recombinant rabbit kidney pyruvate kinase."
    Friesen R.H.E., Chin A.J., Ledman D.W., Lee J.C.
    Biochemistry 37:2949-2960(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
    Tissue: Kidney.
  5. "Isolation and sequence determination of an active site peptide of rabbit muscle pyruvate kinase."
    Bezares G., Eyzaguirre J., Hinrichs M.V., Heinrikson R.L., Reardon I., Kemp R.G., Latshaw S.P., Bazaes S.
    Arch. Biochem. Biophys. 253:133-137(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 343-376.
  6. "Ligand-induced domain movement in pyruvate kinase: structure of the enzyme from rabbit muscle with Mg2+, K+, and L-phospholactate at 2.7-A resolution."
    Larsen T.M., Benning M.M., Wesenberg G.E., Rayment I., Reed G.H.
    Arch. Biochem. Biophys. 345:199-206(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH L-PHOSPHOLACTATE, MAGNESIUM AND POTASSIUM IONS.
    Tissue: Skeletal muscle.
  7. "Structure of the bis(Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 A resolution: ATP binding over a barrel."
    Larsen T.M., Benning M.M., Rayment I., Reed G.H.
    Biochemistry 37:6247-6255(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH OXYLATE AND MAGNESIUM IONS.
    Tissue: Skeletal muscle.

Entry informationi

Entry nameiKPYM_RABIT
AccessioniPrimary (citable) accession number: P11974
Secondary accession number(s): O18919, Q29501
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: November 26, 2014
This is version 143 of the entry and version 4 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