P11980 (KPYM_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyruvate kinase isozymes M1/M2
EC=2.7.1.40

Alternative name(s):
Pyruvate kinase muscle isozyme

Gene names

Name:	Pkm2
Synonyms:	Pykm

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	531 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Catalytic activity	ATP + pyruvate = ADP + phosphoenolpyruvate.
Cofactor	Magnesium. Potassium.
Enzyme regulation	Isoform M2 is allosterically activated by D-fructose 1,6-biphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3) By similarity.
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. Interacts with HERC1 formation induces pyruvate kinase activity. Interacts with HERC1, POU5F1 and PML. Interacts with EGLN3; the interaction hydroxylates PKM2 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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. ISGylated By similarity. Under hypoxia, hydroxylated by EGLN3 By similarity.
Miscellaneous	There are 4 isozymes of pyruvate kinase in mammals: L, R, M1 and M2. 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.
Sequence similarities	Belongs to the pyruvate kinase family.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Pyruvate
Molecular function	Kinase Transferase
PTM	Acetylation Hydroxylation Phosphoprotein Ubl conjugation
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	ATP biosynthetic process Inferred from direct assay. Source: RGD glycolysis Inferred from direct assay. Source: RGD liver development Inferred from direct assay. Source: RGD organ regeneration Inferred from direct assay. Source: RGD pyruvate biosynthetic process Inferred from direct assay. Source: RGD response to gravity Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to insulin stimulus Inferred from expression pattern. Source: RGD response to muscle inactivity Inferred from expression pattern. Source: RGD response to nutrient Inferred from expression pattern. Source: RGD skeletal muscle tissue regeneration Inferred from direct assay. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Inferred from direct assay. Source: RGD
Molecular function	ADP binding Inferred from direct assay. Source: RGD ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: InterPro potassium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: RGD pyruvate kinase activity Inferred from direct assay. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform M1 (identifier: P11980-1)

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 M2 (identifier: P11980-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 531	530	Pyruvate kinase isozymes M1/M2		PRO_0000112092
Regions
	Region	307 – 531	225	Interaction with POU5F1 By similarity
	Region	389 – 433	45	Intersubunit contact
	Region	432 – 437	6	D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity
	Region	514 – 521	8	D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity
Sites
	Metal binding	75	1	Potassium By similarity
	Metal binding	77	1	Potassium By similarity
	Metal binding	113	1	Potassium By similarity
	Metal binding	114	1	Potassium; via carbonyl oxygen By similarity
	Metal binding	272	1	Magnesium By similarity
	Metal binding	296	1	Magnesium By similarity
	Binding site	73	1	Substrate By similarity
	Binding site	295	1	Substrate; via amide nitrogen By similarity
	Binding site	296	1	Substrate; via amide nitrogen By similarity
	Binding site	328	1	Substrate By similarity
	Binding site	482	1	D-fructose 1,6-bisphosphate; part of allosteric site By similarity
	Binding site	489	1	D-fructose 1,6-bisphosphate; part of allosteric site By similarity
	Site	270	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	37	1	Phosphoserine By similarity
	Modified residue	45	1	Phosphothreonine By similarity
	Modified residue	62	1	N6-acetyllysine By similarity
	Modified residue	83	1	Phosphotyrosine By similarity
	Modified residue	89	1	N6-acetyllysine By similarity
	Modified residue	105	1	Phosphotyrosine By similarity
	Modified residue	148	1	Phosphotyrosine By similarity
	Modified residue	166	1	N6-acetyllysine By similarity
	Modified residue	175	1	Phosphotyrosine By similarity
	Modified residue	195	1	Phosphothreonine By similarity
	Modified residue	266	1	N6-acetyllysine By similarity
	Modified residue	328	1	Phosphothreonine By similarity
	Modified residue	408	1	4-hydroxyproline By similarity
Natural variations
	Alternative sequence	389 – 433	45	VFHRL…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2.		VSP_011107

Sequences

	Sequence		Length	Mass (Da)
	Isoform M1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F0B133FDDD5991A9	FASTA	531	57,818
	10 20 30 40 50 60 MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVEM 70 80 90 100 110 120 LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS DPILYRPVAV ALDTKGPEIR 130 140 150 160 170 180 TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL 190 200 210 220 230 240 ISLQVKEKGA DYLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV 250 260 270 280 290 300 FASFIRKAAD 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 IAREAEAAVF HRLLFEELAR ASSQSTDPLE AMAMGSVEAS 430 440 450 460 470 480 YKCLAAALIV LTESGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD 490 500 510 520 530 AWAEDVDLRV NLAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
	Isoform M2 [UniParc] [UniParc]. Checksum: 321D9EB3500272DA	FASTA	531	57,781
	10 20 30 40 50 60 MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVEM 70 80 90 100 110 120 LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS DPILYRPVAV ALDTKGPEIR 130 140 150 160 170 180 TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL 190 200 210 220 230 240 ISLQVKEKGA DYLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV 250 260 270 280 290 300 FASFIRKAAD 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 AAAVGAVEAS 430 440 450 460 470 480 FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD 490 500 510 520 530 AWAEDVDLRV NLAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P

References

[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: 3020052] [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: 2914912] [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: 2780321] [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), MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain, Hippocampus and Spinal cord.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M24359 Genomic DNA. Translation: AAB93666.1. M24359 Genomic DNA. Translation: AAB93667.1. M14377 Genomic DNA. No translation available. X15800 mRNA. Translation: CAA33799.1.
IPI	IPI00231929. IPI00339197.
PIR	A26186. B26186.
RefSeq	NP_445749.1. NM_053297.1.
UniGene	Rn.1556.
3D structure databases
ProteinModelPortal	P11980.
SMR	P11980. Positions 11-531.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11980. 1 interaction.
MINT	MINT-4587504.
STRING	P11980.
PTM databases
PhosphoSite	P11980.
2D gel databases
World-2DPAGE	0004:P11980.
Proteomic databases
PRIDE	P11980.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000015332; ENSRNOP00000015331; ENSRNOG00000011329. ENSRNOT00000015398; ENSRNOP00000015398; ENSRNOG00000011329.
GeneID	25630.
KEGG	rno:25630.
UCSC	NM_053297. rat.
Organism-specific databases
CTD	5315.
RGD	3337. Pkm2.
Phylogenomic databases
eggNOG	maNOG12287.
GeneTree	ENSGT00390000008859.
HOVERGEN	HBG000941.
InParanoid	P11980.
OrthoDB	EOG40GCQJ.
PhylomeDB	P11980.
Gene expression databases
Genevestigator	P11980.
GermOnline	ENSRNOG00000011329. Rattus norvegicus.
Family and domain databases
InterPro	IPR001697. Pyr_Knase. IPR015813. Pyrv/PenolPyrv_Kinase. 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]
Gene3D	G3DSA:2.40.33.10. PK_B_barrel_like. 1 hit. G3DSA:3.20.20.60. Pyrv/PenolPyrv_Kinase_cat. 2 hits. G3DSA:3.40.1380.20. Pyrv_Knase_a/b. 1 hit.
KO	K00873.
PANTHER	PTHR11817. Pyruvate_kinase. 1 hit.
Pfam	PF00224. PK. 1 hit. PF02887. PK_C. 1 hit. [Graphical view]
PRINTS	PR01050. PYRUVTKNASE.
SUPFAM	SSF50800. PK_B_barrel_like. 1 hit. SSF52935. Pyruvate_kinase. 1 hit. SSF51621. Pyrv/PenolPyrv_Kinase_cat. 1 hit.
TIGRFAMs	TIGR01064. Pyruv_kin. 1 hit.
PROSITE	PS00110. PYRUVATE_KINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	607431.

Entry information

Entry name

KPYM_RAT

Accession

Primary (citable) accession number: P11980
Secondary accession number(s): P11981

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program