P30613 (KPYR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Pyruvate kinase 1
R-type/L-type pyruvate kinase
Red cell/liver pyruvate kinase

Gene names

Name:	PKLR
Synonyms:	PK1, PKL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	574 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Glycolysis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hereditary hemolytic anemia
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Pyruvate
Molecular function	Kinase Transferase
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP biosynthetic process Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara endocrine pancreas development Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome glycolysis Traceable author statement. Source: Reactome positive regulation of cellular metabolic process Traceable author statement. Source: Reactome pyruvate biosynthetic process Inferred from electronic annotation. Source: Compara response to ATP Inferred from electronic annotation. Source: Compara response to cAMP Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to lithium ion Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to other organism Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
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 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)

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)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MSIQENISSLQLRSWVSKSQRDLAKSILIGAPG → 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_0000112094

Regions

Region

475 – 480

6

Allosteric activator binding

Region

559 – 564

6

Allosteric activator binding

Sites

Metal binding

118

1

Potassium

Metal binding

120

1

Potassium

Metal binding

156

1

Potassium

Metal binding

157

1

Potassium; via carbonyl oxygen

Metal binding

315

1

Magnesium

Metal binding

339

1

Magnesium

Binding site

116

1

Substrate

Binding site

338

1

Substrate; via amide nitrogen

Binding site

339

1

Substrate; via amide nitrogen

Binding site

371

1

Substrate

Binding site

525

1

Allosteric activator

Binding site

532

1

Allosteric activator

Site

313

1

Transition state stabilizer By similarity

Natural variations

Alternative sequence

1 – 33

33

MSIQE…IGAPG → ME in isoform L-type.

VSP_002883

Natural variant

37

1

G → E in PKHYP. Ref.23

VAR_011435

Natural variant

40

1

R → W in PKRD. Ref.28

VAR_058467

Natural variant

48 – 53

6

Missing in PKRD.

VAR_058468

Natural variant

73

1

L → P in PKRD. Ref.28

VAR_058469

Natural variant

80

1

S → P in PKRD.

VAR_011436

Natural variant

86

1

R → P in PKRD.

VAR_011437

Natural variant

90

1

I → N in PKRD. Ref.28

VAR_011438

Natural variant

95

1

G → R in PKRD.

VAR_011439

Natural variant

107

1

M → T in PKRD.

VAR_004028

Natural variant

111

1

G → R in PKRD. Ref.28

VAR_011440

Natural variant

115

1

A → P in PKRD; Val de Marne.

VAR_011441

Natural variant

120

1

S → F in PKRD; Beaujon.

VAR_011442

Natural variant

130

1

S → Y in PKRD; Conakry. Ref.25

VAR_011443

Natural variant

131

1

Missing in PKRD.

VAR_004029

Natural variant

134

1

V → D in PKRD. Ref.18

VAR_004030

Natural variant

153

1

I → T in PKRD.

VAR_011474

Natural variant

154

1

A → T in PKRD. Ref.28

VAR_058470

Natural variant

155

1

L → P in PKRD. Ref.18

VAR_004031

Natural variant

159

1

G → V in PKRD.

VAR_011444

Natural variant

163

1

R → C in PKRD; Linz. Ref.15

VAR_004033

Natural variant

163

1

R → L in PKRD. Ref.28

VAR_058471

Natural variant

165

1

G → V in PKRD. Ref.28

VAR_058472

Natural variant

172

1

E → Q in PKRD; Sassari. Ref.24

VAR_004032

Natural variant

219

1

I → T in PKRD.

VAR_011475

Natural variant

221

1

D → DD in PKRD.

VAR_004034

Natural variant

222

1

G → A in PKRD; Katsushika.

VAR_011445

Natural variant

263

1

G → R in PKRD.

VAR_011447

Natural variant

263

1

G → W in PKRD.

VAR_011448

Natural variant

272

1

L → V in PKRD. Ref.28

VAR_058473

Natural variant

275

1

G → R in PKRD.

VAR_004035

Natural variant

281

1

D → N in PKRD.

VAR_004036

Natural variant

287

1

F → V in PKRD.

VAR_004037

Natural variant

288

1

V → L in PKRD; Moriguchi.

VAR_011449

Natural variant

293

1

D → N in PKRD.

VAR_011446

Natural variant

295

1

A → V in PKRD.

VAR_011450

Natural variant

310

1

I → N in PKRD; Dordrecht. Ref.28

VAR_011451

Natural variant

314

1

I → T in PKRD; Hong Kong.

VAR_004038

Natural variant

315

1

E → K in PKRD.

VAR_011452

Natural variant

320

1

V → L in PKRD. Ref.28

VAR_058474

Natural variant

331

1

D → E in PKRD; Parma. Ref.21

VAR_004039

Natural variant

331

1

D → N in PKRD.

VAR_011453

Natural variant

332

1

G → S in PKRD; loss of catalytical activity. Ref.14 Ref.20 Ref.26

VAR_004040

Natural variant

335

1

V → M in PKRD. Ref.27

VAR_011476

Natural variant

336

1

A → S in PKRD. Ref.20

VAR_004041

Natural variant

337

1

R → P in PKRD. Ref.26

VAR_004042

Natural variant

337

1

R → Q in PKRD. Ref.24

VAR_004043

Natural variant

339

1

D → H in PKRD. Ref.24

VAR_004044

Natural variant

341

1

G → A in PKRD. Ref.21 Ref.29

VAR_004045

Natural variant

341

1

G → D in PKRD.

VAR_011454

Natural variant

342

1

I → F in PKRD.

VAR_011455

Natural variant

348

1

K → N in PKRD; Kamata.

VAR_011456

Natural variant

348

1

Missing in PKRD; Brescia. Ref.27

VAR_011457

Natural variant

352

1

A → D in PKRD.

VAR_011477

Natural variant

354

1

Missing in PKRD. Ref.20

VAR_004046

Natural variant

357

1

I → T in PKRD. Ref.24

VAR_004047

Natural variant

358

1

G → E in PKRD. Ref.28

VAR_058475

Natural variant

359

1

R → C in PKRD; Aomori.

VAR_004048

Natural variant

359

1

R → H in PKRD. Ref.18

VAR_004049

Natural variant

361

1

N → D in PKRD. Ref.20

VAR_004050

Natural variant

364

1

G → D in PKRD; Tjaereborg; unstability of the protein and decrease in catalytic activity. Ref.14

VAR_011458

Natural variant

368

1

V → F in PKRD; Osaka. Ref.7

VAR_004051

Natural variant

374

1

L → P in PKRD. Ref.28

VAR_058476

Natural variant

376

1

S → I in PKRD.

VAR_011459

Natural variant

384

1

T → M in PKRD; Tokyo/Beirut; most common mutation in Japanese population; no conformational change. Ref.1 Ref.14 Ref.15

VAR_004052

Natural variant

385

1

R → W in PKRD.

VAR_011478

Natural variant

387

1

E → G in PKRD. Ref.27

VAR_011460

Natural variant

390

1

D → N in PKRD; Mantova; almost complete inactivation. Ref.14

VAR_011461

Natural variant

392

1

A → T in PKRD. Ref.20

VAR_004053

Natural variant

393

1

N → K in PKRD. Ref.21

VAR_004054

Natural variant

393

1

N → S in PKRD; Paris. Ref.21

VAR_004055

Natural variant

394

1

A → D in PKRD. Ref.27

VAR_011462

Natural variant

394

1

A → V in PKRD. Ref.27

VAR_011463

Natural variant

401

1

C → CS in PKRD.

VAR_004056

Natural variant

408

1

T → A in PKRD; Hirosaki.

VAR_011464

Natural variant

408

1

T → I in PKRD. Ref.24

VAR_004057

Natural variant

421

1

Q → K in PKRD; Fukushima/Maebashi/Sendai. Ref.16

VAR_004058

Natural variant

426

1

R → Q in PKRD; Sapporo. Ref.17

VAR_004059

Natural variant

426

1

R → W in PKRD; Naniwa.

VAR_004060

Natural variant

427

1

E → A in PKRD.

VAR_011465

Natural variant

427

1

E → D in PKRD.

VAR_011466

Natural variant

431

1

A → T in PKRD. Ref.24

VAR_004061

Natural variant

458

1

G → D in PKRD. Ref.21

VAR_004062

Natural variant

459

1

A → V in PKRD.

VAR_004063

Natural variant

460

1

V → M in PKRD. Ref.21

VAR_004064

Natural variant

468

1

A → G in PKRD.

VAR_011479

Natural variant

468

1

A → V in PKRD; Hadano.

VAR_004065

Natural variant

477

1

T → A in PKRD.

VAR_011467

Natural variant

479

1

R → H in PKRD; Amish; no conformational change. Ref.14 Ref.19

VAR_011480

Natural variant

485

1

S → F in PKRD.

VAR_011468

Natural variant

486

1

R → W in PKRD; frequent mutation; no conformational change. Ref.14 Ref.18 Ref.24 Ref.26

VAR_004066

Natural variant

488

1

R → Q in PKRD.

VAR_011469

Natural variant

490

1

R → W in PKRD.

VAR_004067

Natural variant

495

1

A → T in PKRD.

VAR_011470

Natural variant

495

1

A → V in PKRD. Ref.18

VAR_004068

Natural variant

498

1

R → C in PKRD. Ref.26

VAR_004069

Natural variant

498

1

R → H in PKRD. Ref.20 Ref.21

VAR_004070

Natural variant

504

1

R → L in PKRD; instability of the protein. Ref.14

VAR_011471

Natural variant

506

1

V → I. Ref.4
Corresponds to variant rs8177988 [ dbSNP | Ensembl ].

VAR_018848

Natural variant

510

1

R → Q in PKRD; the most common mutation in European population. Ref.18 Ref.20 Ref.26

VAR_004071

Natural variant

511

1

G → R in PKRD.

VAR_011472

Natural variant

531

1

R → C in PKRD.

VAR_011473

Natural variant

532

1

R → Q in PKRD. Ref.24

VAR_004072

Natural variant

532

1

R → W in PKRD; Complete loss in the responsiveness to fructose 1,6-bisphosphate, FBP. Ref.14 Ref.20

VAR_004073

Natural variant

552

1

V → M in PKRD.

VAR_004074

Natural variant

557

1

G → A in PKRD.

VAR_011481

Natural variant

559

1

R → G in PKRD.

VAR_004075

Natural variant

566

1

N → K in PKRD.

VAR_004076

Natural variant

569

1

R → Q in PKRD. Ref.29

VAR_011482

Experimental info

Sequence conflict

423

1

A → R in AAA60104. Ref.2

Secondary structure

1

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574

Helix Strand Turn

Details...

Turn

49 – 51

3

Helix

55 – 57

3

Helix

61 – 64

4

Helix

69 – 74

6

Beta strand

88 – 93

6

Turn

96 – 98

3

Helix

101 – 110

10

Beta strand

112 – 118

7

Helix

124 – 139

16

Turn

140 – 143

4

Helix

145 – 147

3

Beta strand

152 – 156

5

Beta strand

162 – 164

3

Beta strand

170 – 172

3

Beta strand

175 – 177

3

Beta strand

182 – 186

5

Helix

189 – 191

3

Beta strand

199 – 203

5

Helix

207 – 210

4

Beta strand

216 – 219

4

Turn

220 – 223

4

Beta strand

224 – 232

9

Beta strand

235 – 242

8

Beta strand

244 – 246

3

Beta strand

251 – 253

3

Helix

266 – 277

12

Beta strand

281 – 285

5

Helix

291 – 301

11

Helix

303 – 305

3

Beta strand

309 – 314

6

Helix

317 – 321

5

Helix

323 – 329

7

Beta strand

330 – 336

7

Helix

337 – 343

7

Helix

346 – 348

3

Helix

349 – 363

15

Beta strand

367 – 372

6

Helix

375 – 378

4

Helix

385 – 397

13

Beta strand

400 – 405

6

Helix

406 – 409

4

Helix

414 – 430

17

Helix

434 – 442

9

Helix

451 – 466

16

Beta strand

469 – 474

6

Beta strand

476 – 478

3

Helix

479 – 485

7

Beta strand

490 – 498

9

Helix

500 – 505

6

Helix

506 – 508

3

Beta strand

512 – 516

5

Helix

525 – 542

18

Beta strand

551 – 561

11

Beta strand

565 – 572

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform R-type [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 3B430896832032F5	FASTA	574	61,830
	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
	Isoform L-type [UniParc]. Checksum: CA16D3984B868D9E	FASTA	543	58,494
	10 20 30 40 50 60 MEGPAGYLRR ASVAQLTQEL GTAFFQQQQL PAAMADTFLE HLCLLDIDSE PVAARSTSII 70 80 90 100 110 120 ATIGPASRSV ERLKEMIKAG MNIARLNFSH GSHEYHAESI ANVREAVESF AGSPLSYRPV 130 140 150 160 170 180 AIALDTKGPE IRTGILQGGP ESEVELVKGS QVLVTVDPAF RTRGNANTVW VDYPNIVRVV 190 200 210 220 230 240 PVGGRIYIDD GLISLVVQKI GPEGLVTQVE NGGVLGSRKG VNLPGAQVDL PGLSEQDVRD 250 260 270 280 290 300 LRFGVEHGVD IVFASFVRKA SDVAAVRAAL GPEGHGIKII SKIENHEGVK RFDEILEVSD 310 320 330 340 350 360 GIMVARGDLG IEIPAEKVFL AQKMMIGRCN LAGKPVVCAT QMLESMITKP RPTRAETSDV 370 380 390 400 410 420 ANAVLDGADC IMLSGETAKG NFPVEAVKMQ HAIAREAEAA VYHRQLFEEL RRAAPLSRDP 430 440 450 460 470 480 TEVTAIGAVE AAFKCCAAAI IVLTTTGRSA QLLSRYRPRA AVIAVTRSAQ AARQVHLCRG 490 500 510 520 530 540 VFPLLYREPP EAIWADDVDR RVQFGIESGK LRGFLRVGDL VIVVTGWRPG SGYTNIMRVL SIS

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

NIEHS-SNPs

Wikipedia

Pyruvate kinase entry

PKLR Mutation Database

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.

IPI

IPI00027165.
IPI00941093.

PIR

KIHUPR. I52269.

RefSeq

NP_000289.1. NM_000298.5.
NP_870986.1. NM_181871.3.

UniGene

Hs.95990.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VGB	X-ray	2.73	A/B/C/D	47-574	[»]
2VGF	X-ray	2.75	A/B/C/D	47-574	[»]
2VGG	X-ray	2.74	A/B/C/D	47-574	[»]
2VGI	X-ray	2.87	A/B/C/D	47-574	[»]
4IMA	X-ray	1.95	A/B/C/D	34-574	[»]
4IP7	X-ray	1.80	A/B/C/D	34-574	[»]

ProteinModelPortal

P30613.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30613. 4 interactions.

STRING

9606.ENSP00000339933.

PTM databases

PhosphoSite

P30613.

Polymorphism databases

DMDM

8247933.

2D gel databases

REPRODUCTION-2DPAGE

P30613.

SWISS-2DPAGE

P30613.

Proteomic databases

PaxDb

P30613.

PRIDE

P30613.

Protocols and materials databases

DNASU

5313.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342741; ENSP00000339933; ENSG00000143627.
ENST00000392414; ENSP00000376214; ENSG00000143627.
ENST00000571194; ENSP00000461487; ENSG00000262785.
ENST00000572740; ENSP00000459921; ENSG00000262785.

GeneID

5313.

KEGG

hsa:5313.

UCSC

uc001fka.4. human.
uc001fkb.4. human.

Organism-specific databases

CTD

5313.

GeneCards

GC01M155259.

HGNC

HGNC:9020. PKLR.

HPA

CAB034376.
CAB034378.

MIM

102900. phenotype.
266200. phenotype.
609712. gene.

neXtProt

NX_P30613.

Orphanet

766. Hemolytic anemia due to red cell pyruvate kinase deficiency.

PharmGKB

PA33352.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0469.

HOGENOM

HOG000021559.

HOVERGEN

HBG000941.

KO

K12406.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_111045. Developmental Biology.
REACT_111217. Metabolism.

SABIO-RK

P30613.

UniPathway

UPA00109; UER00188.

Gene expression databases

ArrayExpress

P30613.

Bgee

P30613.

CleanEx

HS_PKLR.

Genevestigator

P30613.

GermOnline

ENSG00000143627. Homo sapiens.

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

ChEMBL

CHEMBL1075126.

DrugBank

DB00119. Pyruvic acid.

EvolutionaryTrace

P30613.

GenomeRNAi

5313.

NextBio

20542.

PMAP-CutDB

P30613.

SOURCE

Search...

Entry information

Entry name

KPYR_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 160 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.