Reviewed, UniProtKB/Swiss-Prot P11980 (KPYM_RAT)

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 POU5F1 and PML By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR 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 Pyruvate
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Allosteric enzyme Direct protein sequencing
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: UniProtKB-KW potassium ion binding Inferred from electronic annotation. Source: InterPro 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
	Active site	270	1	By similarity
	Metal binding	113	1	Potassium By similarity
	Metal binding	114	1	Potassium By similarity
	Metal binding	272	1	Magnesium By similarity
	Metal binding	296	1	Magnesium 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
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	266	1	N6-acetyllysine By similarity
	Modified residue	328	1	Phosphothreonine 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
EMBLGenBankDDBJ	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.
UniGene	Rn.1556
3D structure databases
HSSP	HSSP built from PDB template 1PKN based on UniProtKB P11974.
SMR	P11980. Positions 11-531.
ModBase	Search...
Protein-protein interaction databases
STRING	P11980.
PTM databases
PhosphoSite	P11980.
Proteomic databases
PRIDE	P11980.
Genome annotation databases
Ensembl	ENSRNOT00000015398; ENSRNOP00000015398; ENSRNOG00000011329; Rattus norvegicus. [Genome view] ENSRNOT00000042806; ENSRNOP00000049742; ENSRNOG00000038114; Rattus norvegicus. [Genome view]
GeneID	25630.
KEGG	rno:25630.
UCSC	NM_053297. rat.
Organism-specific databases
CTD	25630.
RGD	3337. Pkm2.
Phylogenomic databases
HOVERGEN	P11980.
Enzyme and pathway databases
BRENDA	2.7.1.40. 248.
Gene expression databases
ArrayExpress	P11980.
Genevestigator	P11980.
GermOnline	ENSRNOG00000011329. Rattus norvegicus.
Family and domain databases
InterPro	IPR001697. Pyr_Knase. IPR015813. Pyrv/PenolPyrv_Kinase_cat. IPR015794. Pyrv_Knase_a/b. IPR018209. Pyrv_Knase_AS. IPR015793. Pyrv_Knase_brl. [Graphical view]
Gene3D	G3DSA:3.20.20.60. Pyrv/PenolPyrv_Kinase_cat. 1 hit. G3DSA:3.40.1380.20. Pyrv_Knase_a/b. 1 hit.
PANTHER	PTHR11817. Pyruvate_kinase. 1 hit.
Pfam	PF00224. PK. 1 hit. PF02887. PK_C. 1 hit. [Graphical view]
PRINTS	PR01050. PYRUVTKNASE.
ProDom	PD001009. Pyruvate_kinase. 2 hits. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR01064. pyruv_kin. 1 hit.
PROSITE	PS00110. PYRUVATE_KINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	October 13, 2009
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)