P12928 (KPYR_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyruvate kinase isozymes R/L
EC=2.7.1.40

Alternative name(s):
L-PK

Gene names

Name:

Pklr

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	574 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Plays a key role in glycolysis By similarity.
Catalytic activity	ATP + pyruvate = ADP + phosphoenolpyruvate.
Cofactor	Magnesium. Potassium.
Enzyme regulation	Allosterically activated by fructose 1,6-bisphosphate By similarity.
Pathway	Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.
Subunit structure	Homotetramer.
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
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Pyruvate
Molecular function	Kinase Transferase
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP biosynthetic process Inferred from direct assay PubMed 4273555PubMed 5492954. Source: RGD cellular response to insulin stimulus Inferred from direct assay PubMed 9395079. Source: RGD glycolysis Inferred from direct assay PubMed 4273555PubMed 4353083. Source: RGD pyruvate biosynthetic process Inferred from direct assay PubMed 4273555PubMed 5492954. Source: RGD response to ATP Inferred from direct assay PubMed 11104754. Source: RGD response to cAMP Inferred from direct assay PubMed 9395079. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 16644726. Source: RGD response to heat Inferred from direct assay PubMed 12417155. Source: RGD response to hypoxia Inferred from expression pattern PubMed 11356723. Source: RGD response to lithium ion Inferred from direct assay PubMed 10700396. Source: RGD response to nutrient Inferred from expression pattern PubMed 11368649. Source: RGD response to other organism Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 1834654. Source: RGD
Molecular_function	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 pyruvate kinase activity Inferred from direct assay PubMed 18062843PubMed 1834654PubMed 4273555PubMed 4353083PubMed 5492954. Source: RGD
Complete GO annotation...

Alternative products

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

Isoform R-type (identifier: P12928-1)

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 L-type (identifier: P12928-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MSVQENTLPQQLWPWIFRSQKDLAKSALSGAPG → ME

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 574	574	Pyruvate kinase isozymes R/L		PRO_0000112096
Regions
	Region	475 – 480	6	Allosteric activator binding By similarity
	Region	559 – 564	6	Allosteric activator binding By similarity
Sites
	Metal binding	118	1	Potassium By similarity
	Metal binding	120	1	Potassium By similarity
	Metal binding	156	1	Potassium By similarity
	Metal binding	157	1	Potassium; via carbonyl oxygen By similarity
	Metal binding	315	1	Magnesium By similarity
	Metal binding	339	1	Magnesium By similarity
	Binding site	116	1	Substrate By similarity
	Binding site	338	1	Substrate; via amide nitrogen By similarity
	Binding site	339	1	Substrate; via amide nitrogen By similarity
	Binding site	371	1	Substrate By similarity
	Binding site	525	1	Allosteric activator By similarity
	Binding site	532	1	Allosteric activator By similarity
	Site	313	1	Transition state stabilizer By similarity
Natural variations
	Alternative sequence	1 – 33	33	MSVQE…SGAPG → ME in isoform L-type.		VSP_002884
Experimental info
	Sequence conflict	130	1	S → Y in AAA41882. Ref.1
	Sequence conflict	130	1	S → Y in AAA41883. Ref.1
	Sequence conflict	322	1	K → R in AAA41882. Ref.1
	Sequence conflict	322	1	K → R in AAA41883. Ref.1
	Sequence conflict	498	1	R → G in AAA41880. Ref.3
	Sequence conflict	501	1	Q → K in AAA41880. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform R-type [UniParc]. Last modified February 1, 1995. Version 2. Checksum: 6BBC544653C51380	FASTA	574	62,200
	10 20 30 40 50 60 MSVQENTLPQ QLWPWIFRSQ KDLAKSALSG APGGPAGYLR RASVAQLTQE LGTAFFQQQQ 70 80 90 100 110 120 LPAAMADTFL EHLCLLDIDS QPVAARSTSI IATIGPASRS VDRLKEMIKA GMNIARLNFS 130 140 150 160 170 180 HGSHEYHAES IANIREATES FATSPLSYRP VAIALDTKGP EIRTGVLQGG PESEVEIVKG 190 200 210 220 230 240 SQVLVTVDPK FQTRGDAKTV WVDYHNITRV VAVGGRIYID DGLISLVVQK IGPEGLVTEV 250 260 270 280 290 300 EHGGILGSRK GVNLPNTEVD LPGLSEQDLL DLRFGVQHNV DIIFASFVRK ASDVLAVRDA 310 320 330 340 350 360 LGPEGQNIKI ISKIENHEGV KKFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC 370 380 390 400 410 420 NLAGKPVVCA TQMLESMITK ARPTRAETSD VANAVLDGAD CIMLSGETAK GSFPVEAVMM 430 440 450 460 470 480 QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EASFKCCAAA IIVLTKTGRS 490 500 510 520 530 540 AQLLSQYRPR AAVIAVTRSA QAARQVHLSR GVFPLLYREP PEAIWADDVD RRVQFGIESG 550 560 570 KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSVS
	Isoform L-type [UniParc]. Checksum: E5472B97649E2A47	FASTA	543	58,794
	10 20 30 40 50 60 MEGPAGYLRR ASVAQLTQEL GTAFFQQQQL PAAMADTFLE HLCLLDIDSQ PVAARSTSII 70 80 90 100 110 120 ATIGPASRSV DRLKEMIKAG MNIARLNFSH GSHEYHAESI ANIREATESF ATSPLSYRPV 130 140 150 160 170 180 AIALDTKGPE IRTGVLQGGP ESEVEIVKGS QVLVTVDPKF QTRGDAKTVW VDYHNITRVV 190 200 210 220 230 240 AVGGRIYIDD GLISLVVQKI GPEGLVTEVE HGGILGSRKG VNLPNTEVDL PGLSEQDLLD 250 260 270 280 290 300 LRFGVQHNVD IIFASFVRKA SDVLAVRDAL GPEGQNIKII SKIENHEGVK KFDEILEVSD 310 320 330 340 350 360 GIMVARGDLG IEIPAEKVFL AQKMMIGRCN LAGKPVVCAT QMLESMITKA RPTRAETSDV 370 380 390 400 410 420 ANAVLDGADC IMLSGETAKG SFPVEAVMMQ HAIAREAEAA VYHRQLFEEL RRAAPLSRDP 430 440 450 460 470 480 TEVTAIGAVE ASFKCCAAAI IVLTKTGRSA QLLSQYRPRA AVIAVTRSAQ AARQVHLSRG 490 500 510 520 530 540 VFPLLYREPP EAIWADDVDR RVQFGIESGK LRGFLRVGDL VIVVTGWRPG SGYTNIMRVL SVS

References

[1]	"The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters." Noguchi T., Yamada K., Inoue H., Matsuda T., Tanaka T. J. Biol. Chem. 262:14366-14371(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete amino acid sequence of rat L-type pyruvate kinase deduced from the cDNA sequence." Inoue H., Noguchi T., Tanaka T. Eur. J. Biochem. 154:465-469(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete nucleotide and deduced amino acid sequences of rat L-type pyruvate kinase." Lone Y.-C., Simon M.-P., Kahn A., Marie J. FEBS Lett. 195:97-100(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Structure of the rat L-type pyruvate kinase gene." Cognet M., Lone Y.C., Vaulont S., Kahn A., Marie J. J. Mol. Biol. 196:11-25(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M17091 , M17088, M17089, M17090 Genomic DNA. Translation: AAA41882.1. M17091 , M17088, M17089, M17090 Genomic DNA. Translation: AAA41883.1. M17685 mRNA. Translation: AAA41881.1. X05684 Genomic DNA. Translation: CAA29169.1. M11709 mRNA. Translation: AAA41880.1.
IPI	IPI00202549. IPI00231683.
PIR	KIRTPR. A27427. KIRTPL. A92940.
RefSeq	NP_036756.3. NM_012624.3.
UniGene	Rn.48821.
3D structure databases
ProteinModelPortal	P12928.
SMR	P12928. Positions 57-573.
ModBase	Search...
PTM databases
PhosphoSite	P12928.
Proteomic databases
PaxDb	P12928.
PRIDE	P12928.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000027700; ENSRNOP00000027700; ENSRNOG00000020420. ENSRNOT00000065791; ENSRNOP00000058886; ENSRNOG00000020420.
GeneID	24651.
KEGG	rno:24651.
UCSC	RGD:3336. rat.
Organism-specific databases
CTD	5313.
RGD	3336. Pklr.
Phylogenomic databases
eggNOG	COG0469.
GeneTree	ENSGT00390000008859.
HOGENOM	HOG000021559.
HOVERGEN	HBG000941.
InParanoid	P12928.
KO	K12406.
OMA	IHTIVKV.
OrthoDB	EOG40GCQJ.
Enzyme and pathway databases
SABIO-RK	P12928.
UniPathway	UPA00109; UER00188.
Gene expression databases
ArrayExpress	P12928.
Genevestigator	P12928.
GermOnline	ENSRNOG00000020420. Rattus norvegicus.
Family and domain databases
Gene3D	2.40.33.10. 1 hit. 3.20.20.60. 2 hits. 3.40.1380.20. 1 hit.
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]
PANTHER	PTHR11817. PTHR11817. 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
BindingDB	P12928.
ChEMBL	CHEMBL3089.
NextBio	603974.

Entry information

Entry name

KPYR_RAT

Accession

Primary (citable) accession number: P12928
Secondary accession number(s): P04763, Q64618

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program