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P30613 (KPYR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 173. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pyruvate kinase PKLR

EC=2.7.1.40
Alternative name(s):
Pyruvate kinase 1
Pyruvate kinase isozymes L/R
R-type/L-type pyruvate kinase
Red cell/liver pyruvate kinase
Gene names
Name:PKLR
Synonyms:PK1, PKL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length574 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. Ref.14

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.

Subunit structure

Homotetramer. Ref.14

Involvement in disease

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23

Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29

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 processGlycolysis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Hereditary hemolytic anemia
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Potassium
Pyruvate
   Molecular functionKinase
Transferase
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Traceable author statement. Source: Reactome

energy reserve metabolic process

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

glycolytic process

Traceable author statement. Source: Reactome

positive regulation of cellular metabolic process

Traceable author statement. Source: Reactome

pyruvate biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to ATP

Inferred from electronic annotation. Source: Ensembl

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to lithium ion

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to other organism

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

   Molecular_functionATP 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

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform R-type (identifier: P30613-1)

Also known as: PKR;

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: P30613-2)

Also known as: PKL;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 574574Pyruvate kinase PKLR
PRO_0000112094

Regions

Region475 – 4806Allosteric activator binding
Region559 – 5646Allosteric activator binding

Sites

Metal binding1181Potassium
Metal binding1201Potassium
Metal binding1561Potassium
Metal binding1571Potassium; via carbonyl oxygen
Metal binding3151Magnesium
Metal binding3391Magnesium
Binding site1161Substrate
Binding site3381Substrate; via amide nitrogen
Binding site3391Substrate; via amide nitrogen
Binding site3711Substrate
Binding site5251Allosteric activator
Binding site5321Allosteric activator
Site3131Transition state stabilizer By similarity

Natural variations

Alternative sequence1 – 3333MSIQE…IGAPG → ME in isoform L-type.
VSP_002883
Natural variant371G → E in PKHYP. Ref.23
VAR_011435
Natural variant401R → W in PKRD. Ref.28
VAR_058467
Natural variant48 – 536Missing in PKRD.
VAR_058468
Natural variant731L → P in PKRD. Ref.28
VAR_058469
Natural variant801S → P in PKRD.
VAR_011436
Natural variant861R → P in PKRD.
VAR_011437
Natural variant901I → N in PKRD. Ref.28
VAR_011438
Natural variant951G → R in PKRD.
VAR_011439
Natural variant1071M → T in PKRD.
VAR_004028
Natural variant1111G → R in PKRD. Ref.28
VAR_011440
Natural variant1151A → P in PKRD; Val de Marne.
VAR_011441
Natural variant1201S → F in PKRD; Beaujon.
VAR_011442
Natural variant1301S → Y in PKRD; Conakry. Ref.25
VAR_011443
Natural variant1311Missing in PKRD.
VAR_004029
Natural variant1341V → D in PKRD. Ref.18
VAR_004030
Natural variant1531I → T in PKRD.
VAR_011474
Natural variant1541A → T in PKRD. Ref.28
VAR_058470
Natural variant1551L → P in PKRD. Ref.18
VAR_004031
Natural variant1591G → V in PKRD.
VAR_011444
Natural variant1631R → C in PKRD; Linz. Ref.15
VAR_004033
Natural variant1631R → L in PKRD. Ref.28
VAR_058471
Natural variant1651G → V in PKRD. Ref.28
VAR_058472
Natural variant1721E → Q in PKRD; Sassari. Ref.24
VAR_004032
Natural variant2191I → T in PKRD.
VAR_011475
Natural variant2211D → DD in PKRD.
VAR_004034
Natural variant2221G → A in PKRD; Katsushika.
VAR_011445
Natural variant2631G → R in PKRD.
VAR_011447
Natural variant2631G → W in PKRD.
VAR_011448
Natural variant2721L → V in PKRD. Ref.28
VAR_058473
Natural variant2751G → R in PKRD.
VAR_004035
Natural variant2811D → N in PKRD.
VAR_004036
Natural variant2871F → V in PKRD.
VAR_004037
Natural variant2881V → L in PKRD; Moriguchi.
VAR_011449
Natural variant2931D → N in PKRD.
VAR_011446
Natural variant2951A → V in PKRD.
VAR_011450
Natural variant3101I → N in PKRD; Dordrecht. Ref.28
VAR_011451
Natural variant3141I → T in PKRD; Hong Kong.
VAR_004038
Natural variant3151E → K in PKRD.
VAR_011452
Natural variant3201V → L in PKRD. Ref.28
VAR_058474
Natural variant3311D → E in PKRD; Parma. Ref.21
VAR_004039
Natural variant3311D → N in PKRD.
VAR_011453
Natural variant3321G → S in PKRD; loss of catalytical activity. Ref.14 Ref.20 Ref.26
VAR_004040
Natural variant3351V → M in PKRD. Ref.27
VAR_011476
Natural variant3361A → S in PKRD. Ref.20
VAR_004041
Natural variant3371R → P in PKRD. Ref.26
VAR_004042
Natural variant3371R → Q in PKRD. Ref.24
VAR_004043
Natural variant3391D → H in PKRD. Ref.24
VAR_004044
Natural variant3411G → A in PKRD. Ref.21 Ref.29
VAR_004045
Natural variant3411G → D in PKRD.
VAR_011454
Natural variant3421I → F in PKRD.
VAR_011455
Natural variant3481K → N in PKRD; Kamata.
VAR_011456
Natural variant3481Missing in PKRD; Brescia. Ref.27
VAR_011457
Natural variant3521A → D in PKRD.
VAR_011477
Natural variant3541Missing in PKRD. Ref.20
VAR_004046
Natural variant3571I → T in PKRD. Ref.24
VAR_004047
Natural variant3581G → E in PKRD. Ref.28
VAR_058475
Natural variant3591R → C in PKRD; Aomori.
VAR_004048
Natural variant3591R → H in PKRD. Ref.18
VAR_004049
Natural variant3611N → D in PKRD. Ref.20
VAR_004050
Natural variant3641G → D in PKRD; Tjaereborg; unstability of the protein and decrease in catalytic activity. Ref.14
VAR_011458
Natural variant3681V → F in PKRD; Osaka. Ref.7
VAR_004051
Natural variant3741L → P in PKRD. Ref.28
VAR_058476
Natural variant3761S → I in PKRD.
VAR_011459
Natural variant3841T → M in PKRD; Tokyo/Beirut; most common mutation in Japanese population; no conformational change. Ref.1 Ref.14 Ref.15
VAR_004052
Natural variant3851R → W in PKRD.
VAR_011478
Natural variant3871E → G in PKRD. Ref.27
VAR_011460
Natural variant3901D → N in PKRD; Mantova; almost complete inactivation. Ref.14
VAR_011461
Natural variant3921A → T in PKRD. Ref.20
VAR_004053
Natural variant3931N → K in PKRD. Ref.21
VAR_004054
Natural variant3931N → S in PKRD; Paris. Ref.21
VAR_004055
Natural variant3941A → D in PKRD. Ref.27
VAR_011462
Natural variant3941A → V in PKRD. Ref.27
VAR_011463
Natural variant4011C → CS in PKRD.
VAR_004056
Natural variant4081T → A in PKRD; Hirosaki.
VAR_011464
Natural variant4081T → I in PKRD. Ref.24
VAR_004057
Natural variant4211Q → K in PKRD; Fukushima/Maebashi/Sendai. Ref.16
VAR_004058
Natural variant4261R → Q in PKRD; Sapporo. Ref.17
VAR_004059
Natural variant4261R → W in PKRD; Naniwa.
VAR_004060
Natural variant4271E → A in PKRD.
VAR_011465
Natural variant4271E → D in PKRD.
VAR_011466
Natural variant4311A → T in PKRD. Ref.24
VAR_004061
Natural variant4581G → D in PKRD. Ref.21
VAR_004062
Natural variant4591A → V in PKRD.
VAR_004063
Natural variant4601V → M in PKRD. Ref.21
VAR_004064
Natural variant4681A → G in PKRD.
VAR_011479
Natural variant4681A → V in PKRD; Hadano.
VAR_004065
Natural variant4771T → A in PKRD.
VAR_011467
Natural variant4791R → H in PKRD; Amish; no conformational change. Ref.14 Ref.19
VAR_011480
Natural variant4851S → F in PKRD.
VAR_011468
Natural variant4861R → W in PKRD; frequent mutation; no conformational change. Ref.14 Ref.18 Ref.24 Ref.26
Corresponds to variant rs116100695 [ dbSNP | Ensembl ].
VAR_004066
Natural variant4881R → Q in PKRD.
VAR_011469
Natural variant4901R → W in PKRD.
Corresponds to variant rs200133000 [ dbSNP | Ensembl ].
VAR_004067
Natural variant4951A → T in PKRD.
VAR_011470
Natural variant4951A → V in PKRD. Ref.18
VAR_004068
Natural variant4981R → C in PKRD. Ref.26
VAR_004069
Natural variant4981R → H in PKRD. Ref.20 Ref.21
VAR_004070
Natural variant5041R → L in PKRD; instability of the protein. Ref.14
Corresponds to variant rs185753709 [ dbSNP | Ensembl ].
VAR_011471
Natural variant5061V → I. Ref.4
Corresponds to variant rs8177988 [ dbSNP | Ensembl ].
VAR_018848
Natural variant5101R → Q in PKRD; the most common mutation in European population. Ref.18 Ref.20 Ref.26
Corresponds to variant rs113403872 [ dbSNP | Ensembl ].
VAR_004071
Natural variant5111G → R in PKRD.
VAR_011472
Natural variant5311R → C in PKRD.
VAR_011473
Natural variant5321R → Q in PKRD. Ref.24
VAR_004072
Natural variant5321R → W in PKRD; Complete loss in the responsiveness to fructose 1,6-bisphosphate, FBP. Ref.14 Ref.20
VAR_004073
Natural variant5521V → M in PKRD.
VAR_004074
Natural variant5571G → A in PKRD.
VAR_011481
Natural variant5591R → G in PKRD.
VAR_004075
Natural variant5661N → K in PKRD.
VAR_004076
Natural variant5691R → Q in PKRD. Ref.29
Corresponds to variant rs61755431 [ dbSNP | Ensembl ].
VAR_011482

Experimental info

Sequence conflict4231A → R in AAA60104. Ref.2

Secondary structure

.................................................................................................... 574
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform R-type (PKR) [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 3B430896832032F5

FASTA57461,830
        10         20         30         40         50         60 
MSIQENISSL QLRSWVSKSQ RDLAKSILIG APGGPAGYLR RASVAQLTQE LGTAFFQQQQ 

        70         80         90        100        110        120 
LPAAMADTFL EHLCLLDIDS EPVAARSTSI IATIGPASRS VERLKEMIKA GMNIARLNFS 

       130        140        150        160        170        180 
HGSHEYHAES IANVREAVES FAGSPLSYRP VAIALDTKGP EIRTGILQGG PESEVELVKG 

       190        200        210        220        230        240 
SQVLVTVDPA FRTRGNANTV WVDYPNIVRV VPVGGRIYID DGLISLVVQK IGPEGLVTQV 

       250        260        270        280        290        300 
ENGGVLGSRK GVNLPGAQVD LPGLSEQDVR DLRFGVEHGV DIVFASFVRK ASDVAAVRAA 

       310        320        330        340        350        360 
LGPEGHGIKI ISKIENHEGV KRFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC 

       370        380        390        400        410        420 
NLAGKPVVCA TQMLESMITK PRPTRAETSD VANAVLDGAD CIMLSGETAK GNFPVEAVKM 

       430        440        450        460        470        480 
QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EAAFKCCAAA IIVLTTTGRS 

       490        500        510        520        530        540 
AQLLSRYRPR AAVIAVTRSA QAARQVHLCR GVFPLLYREP PEAIWADDVD RRVQFGIESG 

       550        560        570 
KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSIS 

« Hide

Isoform L-type (PKL) [UniParc].

Checksum: CA16D3984B868D9E
Show »

FASTA54358,494

References

« Hide 'large scale' references
[1]"cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384-->Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia."
Kanno H., Fujii H., Hirono A., Miwa S.
Proc. Natl. Acad. Sci. U.S.A. 88:8218-8221(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PKRD MET-384.
[2]"Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells."
Tani K., Fujii H., Nagata S., Miwa S.
Proc. Natl. Acad. Sci. U.S.A. 85:1792-1795(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Kanno H.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 130 AND 232.
[4]NIEHS SNPs program
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-506.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM R-TYPE).
Tissue: Pancreas.
[6]"Human liver type pyruvate kinase: cDNA cloning and chromosomal assignment."
Tani K., Fujii H., Tsutsumi H., Sukegawa J., Toyoshima K., Yoshida M.C., Noguchi T., Tanaka T., Miwa S.
Biochem. Biophys. Res. Commun. 143:431-438(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 470-574.
[7]"Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK."
Kanno H., Fujii H., Tsujino G., Miwa S.
Biochem. Biophys. Res. Commun. 192:46-52(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 365-431, VARIANT PKRD PHE-368.
[8]"Mutations in pyruvate kinase."
Beutler E., Baronciani L.
Hum. Mutat. 7:1-6(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[9]"Hematologically important mutations: red cell pyruvate kinase."
Baronciani L., Bianchi P., Zanella A.
Blood Cells Mol. Dis. 22:85-89(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[10]"Hematologically important mutations: red cell pyruvate kinase (1st update)."
Baronciani L., Bianchi P., Zanella A.
Blood Cells Mol. Dis. 22:259-264(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[11]"Hematologically important mutations: red cell pyruvate kinase (2nd update)."
Baronciani L., Bianchi P., Zanella A.
Blood Cells Mol. Dis. 24:273-279(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[12]"Hematologically important mutations: red cell pyruvate kinase (third update)."
Bianchi P., Zanella A.
Blood Cells Mol. Dis. 26:47-53(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia."
Valentini G., Chiarelli L.R., Fortin R., Dolzan M., Galizzi A., Abraham D.J., Wang C., Bianchi P., Zanella A., Mattevi A.
J. Biol. Chem. 277:23807-23814(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 47-574 IN COMPLEX WITH FRUCTOSE 1,6-BISPHOSPHATE, ALLOSTERIC ACTIVATION, ENZYME REGULATION, CHARACTERIZATION OF VARIANTS PKRD SER-332; ASP-364; ASN-390; HIS-479; TRP-486; LEU-504 AND TRP-532, CHARACTERIZATION OF VARIANT MET-384, SUBUNIT.
[15]"Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency."
Neubauer B., Lakomek M., Winkler H., Parke M., Hofferbert S., Schroter W.
Blood 77:1871-1875(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD CYS-163 AND MET-384.
[16]"Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in unrelated PK variants associated with hereditary hemolytic anemia."
Kanno H., Fujii H., Hirono A., Omine M., Miwa S.
Blood 79:1347-1350(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKRD LYS-421.
[17]"Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia."
Kanno H., Fujii H., Miwa S.
Blood 81:2439-2441(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKRD GLN-426.
[18]"Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia."
Baronciani L., Beutler E.
Proc. Natl. Acad. Sci. U.S.A. 90:4324-4327(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD ASP-134; PRO-155; HIS-359; TRP-486; VAL-495 AND GLN-510.
[19]"Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish."
Kanno H., Ballas S.K., Miwa S., Fujii H., Bowman H.S.
Blood 83:2311-2316(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKRD HIS-479.
[20]"Mutations in the pyruvate kinase L gene in patients with hereditary hemolytic anemia."
Lenzner C., Nuernberg P., Thiele B.-J., Reis A., Brabec V., Sakalova A., Jacobasch G.
Blood 83:2817-2822(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD SER-332; SER-336; LYS-354 DEL; ASP-361; THR-392; HIS-498; GLN-510 AND TRP-532.
[21]"Molecular study of pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia."
Baronciani L., Beutler E.
J. Clin. Invest. 95:1702-1709(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD GLU-331; ALA-341; LYS-393; SER-393; ASP-458; MET-460 AND HIS-498.
[22]"Study of the molecular defects in pyruvate kinase (PK) deficient patients affected by hereditary nonspherocytic hemolytic anemia (HNHA)."
Baronciani L., Westwood B., Beutler E.
J. Invest. Med. 43:341A-341A(1995)
Cited for: VARIANTS PKRD.
[23]"G-to-T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene is the molecular basis of a case of hereditary increase of red blood cell ATP."
Beutler E., Westwood B., van Zwieten R., Roos D.
Hum. Mutat. 9:282-285(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKHYP GLU-37.
[24]"Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients."
Zarza R., Alvarez R., Pujades A., Nomdedeu B., Carrera A., Estella J., Remacha A., Sanchez J.M., Morey M., Cortes T., Perez Lungmus G., Bureo E., Vives Corrons J.L.
Br. J. Haematol. 103:377-382(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD GLN-172; GLN-337; HIS-339; THR-357; ILE-408; THR-431; TRP-486 AND GLN-532.
[25]"A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha-2 globin gene variant (Hb Conakry)."
Cohen-Solal M., Prehu C., Wajcman H., Poyart C., Bardakdjian-Michau J., Kister J., Prome D., Valentin C., Bachir D., Galacteros F.
Br. J. Haematol. 103:950-956(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKRD TYR-130.
[26]"Novel mutations and structural implications in R-type pyruvate kinase-deficient patients from Southern Italy."
Pastore L., della Morte R., Frisso G., Alfinito F., Vitale D., Calise R.M., Ferraro F., Zagari A., Rotoli B., Salvatore F.
Hum. Mutat. 11:127-134(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD SER-332; PRO-337; TRP-486; CYS-498 AND GLN-510.
[27]"Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients."
Zanella A., Bianchi P., Fermo E., Iurlo A., Zappa M., Vercellati C., Boschetti C., Baronciani L., Cotton F.
Br. J. Haematol. 113:43-48(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD MET-335; LYS-348 DEL; GLY-387; ASP-394 AND VAL-394.
[28]"Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK."
van Wijk R., Huizinga E.G., van Wesel A.C.W., van Oirschot B.A., Hadders M.A., van Solinge W.W.
Hum. Mutat. 30:446-453(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD TRP-40; 48-THR--THR-53 DEL; PRO-73; ASN-90; ARG-111; THR-154; LEU-163; VAL-165; VAL-272; ASN-310; LEU-320; GLU-358 AND PRO-374.
[29]"Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications."
Lyon G.J., Jiang T., Van Wijk R., Wang W., Bodily P.M., Xing J., Tian L., Robison R.J., Clement M., Lin Y., Zhang P., Liu Y., Moore B., Glessner J.T., Elia J., Reimherr F., van Solinge W.W., Yandell M. expand/collapse author list , Hakonarson H., Wang J., Johnson W.E., Wei Z., Wang K.
Discov. Med. 12:41-55(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKRD ALA-341 AND GLN-569.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB015983 mRNA. Translation: BAA31706.1.
M15465 mRNA. Translation: AAA60104.1.
AY316591 Genomic DNA. Translation: AAP69527.1.
BC025737 mRNA. Translation: AAH25737.1.
S60712 mRNA. Translation: AAB26262.1.
CCDSCCDS1109.1. [P30613-1]
CCDS44240.1. [P30613-2]
PIRKIHUPR. I52269.
RefSeqNP_000289.1. NM_000298.5. [P30613-1]
NP_870986.1. NM_181871.3. [P30613-2]
UniGeneHs.95990.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VGBX-ray2.73A/B/C/D47-574[»]
2VGFX-ray2.75A/B/C/D47-574[»]
2VGGX-ray2.74A/B/C/D47-574[»]
2VGIX-ray2.87A/B/C/D47-574[»]
4IMAX-ray1.95A/B/C/D34-574[»]
4IP7X-ray1.80A/B/C/D34-574[»]
ProteinModelPortalP30613.
SMRP30613. Positions 57-573.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111330. 12 interactions.
IntActP30613. 5 interactions.
STRING9606.ENSP00000339933.

Chemistry

ChEMBLCHEMBL1075126.
DrugBankDB00119. Pyruvic acid.

PTM databases

PhosphoSiteP30613.

2D gel databases

REPRODUCTION-2DPAGEP30613.
SWISS-2DPAGEP30613.

Proteomic databases

MaxQBP30613.
PaxDbP30613.
PRIDEP30613.

Protocols and materials databases

DNASU5313.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342741; ENSP00000339933; ENSG00000143627. [P30613-1]
ENST00000392414; ENSP00000376214; ENSG00000143627. [P30613-2]
ENST00000571194; ENSP00000461487; ENSG00000262785. [P30613-2]
ENST00000572740; ENSP00000459921; ENSG00000262785. [P30613-1]
GeneID5313.
KEGGhsa:5313.
UCSCuc001fka.4. human. [P30613-2]
uc001fkb.4. human. [P30613-1]

Organism-specific databases

CTD5313.
GeneCardsGC01M155259.
HGNCHGNC:9020. PKLR.
HPACAB034376.
CAB034378.
MIM102900. phenotype.
266200. phenotype.
609712. gene.
neXtProtNX_P30613.
Orphanet766. Hemolytic anemia due to red cell pyruvate kinase deficiency.
PharmGKBPA33352.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0469.
HOGENOMHOG000021559.
HOVERGENHBG000941.
KOK12406.
OMACVTRNEQ.
PhylomeDBP30613.
TreeFamTF300390.

Enzyme and pathway databases

BioCycMetaCyc:HS07088-MONOMER.
ReactomeREACT_111045. Developmental Biology.
REACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP30613.
UniPathwayUPA00109; UER00188.

Gene expression databases

ArrayExpressP30613.
BgeeP30613.
CleanExHS_PKLR.
GenevestigatorP30613.

Family and domain databases

Gene3D2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProIPR001697. 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]
PANTHERPTHR11817. PTHR11817. 1 hit.
PfamPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSPR01050. PYRUVTKNASE.
SUPFAMSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsTIGR01064. pyruv_kin. 1 hit.
PROSITEPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP30613.
GeneWikiPKLR.
GenomeRNAi5313.
NextBio20542.
PMAP-CutDBP30613.
PROP30613.
SOURCESearch...

Entry information

Entry nameKPYR_HUMAN
AccessionPrimary (citable) accession number: P30613
Secondary accession number(s): P11973
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: May 30, 2000
Last modified: July 9, 2014
This is version 173 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM