ID KPYR_HUMAN Reviewed; 574 AA. AC P30613; O75758; P11973; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 24-JAN-2024, entry version 250. DE RecName: Full=Pyruvate kinase PKLR; DE EC=2.7.1.40 {ECO:0000269|PubMed:11960989}; DE AltName: Full=Pyruvate kinase 1; DE AltName: Full=Pyruvate kinase isozymes L/R; DE AltName: Full=R-type/L-type pyruvate kinase; DE AltName: Full=Red cell/liver pyruvate kinase; GN Name=PKLR; Synonyms=PK1, PKL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PKRD MET-384. RX PubMed=1896471; DOI=10.1073/pnas.88.18.8218; RA Kanno H., Fujii H., Hirono A., Miwa S.; RT "cDNA cloning of human R-type pyruvate kinase and identification of a RT single amino acid substitution (Thr384-->Met) affecting enzymatic stability RT in a pyruvate kinase variant (PK Tokyo) associated with hereditary RT hemolytic anemia."; RL Proc. Natl. Acad. Sci. U.S.A. 88:8218-8221(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3126495; DOI=10.1073/pnas.85.6.1792; RA Tani K., Fujii H., Nagata S., Miwa S.; RT "Human liver type pyruvate kinase: complete amino acid sequence and the RT expression in mammalian cells."; RL Proc. Natl. Acad. Sci. U.S.A. 85:1792-1795(1988). RN [3] RP SEQUENCE REVISION TO 130 AND 232. RA Kanno H.; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1445295; DOI=10.1016/0006-291x(92)91086-6; RA Kanno H., Fujii H., Miwa S.; RT "Structural analysis of human pyruvate kinase L-gene and identification of RT the promoter activity in erythroid cells."; RL Biochem. Biophys. Res. Commun. 188:516-523(1992). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-506. RG NIEHS SNPs program; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM R-TYPE). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 470-574. RX PubMed=3566732; DOI=10.1016/0006-291x(87)91372-6; RA Tani K., Fujii H., Tsutsumi H., Sukegawa J., Toyoshima K., Yoshida M.C., RA Noguchi T., Tanaka T., Miwa S.; RT "Human liver type pyruvate kinase: cDNA cloning and chromosomal RT assignment."; RL Biochem. Biophys. Res. Commun. 143:431-438(1987). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 365-431, AND VARIANT PKRD PHE-368. RX PubMed=8476433; DOI=10.1006/bbrc.1993.1379; RA Kanno H., Fujii H., Tsujino G., Miwa S.; RT "Molecular basis of impaired pyruvate kinase isozyme conversion in RT erythroid cells: a single amino acid substitution near the active site and RT decreased mRNA content of the R-type PK."; RL Biochem. Biophys. Res. Commun. 192:46-52(1993). RN [9] RP REVIEW, AND VARIANTS PKRD THR-107; ARG-275; ASN-281; VAL-287; THR-314; RP CYS-359; TRP-426; VAL-459; VAL-468; TRP-490; MET-552; GLY-559 AND LYS-566. RX PubMed=8664896; RX DOI=10.1002/(sici)1098-1004(1996)7:1<1::aid-humu1>3.0.co;2-h; RA Beutler E., Baronciani L.; RT "Mutations in pyruvate kinase."; RL Hum. Mutat. 7:1-6(1996). RN [10] RP REVIEW, AND VARIANTS PKRD PRO-80; ILE-131 DEL; ASP-221 INS AND ASN-281. RX PubMed=8807089; DOI=10.1006/bcmd.1996.0012; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase."; RL Blood Cells Mol. Dis. 22:85-89(1996). RN [11] RP REVIEW, AND VARIANTS PKRD PRO-115; PHE-120; ARG-263; TRP-263; ASN-331; RP PHE-342; ASP-352; ASP-427; PHE-485 AND THR-495. RX PubMed=9075576; DOI=10.1006/bcmd.1996.0107; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (1st RT update)."; RL Blood Cells Mol. Dis. 22:259-264(1996). RN [12] RP REVIEW, AND VARIANTS PKRD PRO-86; ARG-95; ALA-222; LEU-288; VAL-295; RP LYS-315; ASP-341; ASN-348; ILE-376; SER-401 INS; ALA-408; ALA-427; ALA-477; RP GLN-488; ARG-511 AND CYS-531. RX PubMed=10087985; DOI=10.1006/bcmd.1998.0193; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (2nd RT update)."; RL Blood Cells Mol. Dis. 24:273-279(1998). RN [13] RP REVIEW, AND VARIANTS PKRD THR-153; VAL-159; ASN-293; ASP-352; TRP-385; RP GLY-468 AND ALA-557. RX PubMed=10772876; DOI=10.1006/bcmd.2000.0276; RA Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (third RT update)."; RL Blood Cells Mol. Dis. 26:47-53(2000). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-19 AND SER-26, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43 AND SER-292, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 47-574 IN COMPLEX WITH SUBSTRATE RP ANALOG; FRUCTOSE 1,6-BISPHOSPHATE; POTASSIUM IONS AND MANGANESE IONS, RP FUNCTION, CATALYTIC ACTIVITY, ALLOSTERIC ACTIVATION, ACTIVITY REGULATION, RP CHARACTERIZATION OF VARIANTS PKRD SER-332; ASP-364; ASN-390; HIS-479; RP TRP-486; LEU-504 AND TRP-532, CHARACTERIZATION OF VARIANT MET-384, AND RP SUBUNIT. RX PubMed=11960989; DOI=10.1074/jbc.m202107200; RA Valentini G., Chiarelli L.R., Fortin R., Dolzan M., Galizzi A., RA Abraham D.J., Wang C., Bianchi P., Zanella A., Mattevi A.; RT "Structure and function of human erythrocyte pyruvate kinase. Molecular RT basis of nonspherocytic hemolytic anemia."; RL J. Biol. Chem. 277:23807-23814(2002). RN [17] RP VARIANTS PKRD CYS-163 AND MET-384. RX PubMed=2018831; RA Neubauer B., Lakomek M., Winkler H., Parke M., Hofferbert S., Schroter W.; RT "Point mutations in the L-type pyruvate kinase gene of two children with RT hemolytic anemia caused by pyruvate kinase deficiency."; RL Blood 77:1871-1875(1991). RN [18] RP VARIANT PKRD LYS-421. RX PubMed=1536957; RA Kanno H., Fujii H., Hirono A., Omine M., Miwa S.; RT "Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in RT unrelated PK variants associated with hereditary hemolytic anemia."; RL Blood 79:1347-1350(1992). RN [19] RP VARIANT PKRD GLN-426. RX PubMed=8481523; RA Kanno H., Fujii H., Miwa S.; RT "Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a RT single amino acid substitution (426 Arg-->Gln) associated with hereditary RT hemolytic anemia."; RL Blood 81:2439-2441(1993). RN [20] RP VARIANTS PKRD ASP-134; PRO-155; HIS-359; TRP-486; VAL-495 AND GLN-510. RX PubMed=8483951; DOI=10.1073/pnas.90.9.4324; RA Baronciani L., Beutler E.; RT "Analysis of pyruvate kinase-deficiency mutations that produce RT nonspherocytic hemolytic anemia."; RL Proc. Natl. Acad. Sci. U.S.A. 90:4324-4327(1993). RN [21] RP VARIANT PKRD HIS-479. RX PubMed=8161798; RA Kanno H., Ballas S.K., Miwa S., Fujii H., Bowman H.S.; RT "Molecular abnormality of erythrocyte pyruvate kinase deficiency in the RT Amish."; RL Blood 83:2311-2316(1994). RN [22] RP VARIANTS PKRD SER-332; SER-336; LYS-354 DEL; ASP-361; THR-392; HIS-498; RP GLN-510 AND TRP-532. RX PubMed=8180378; RA Lenzner C., Nuernberg P., Thiele B.-J., Reis A., Brabec V., Sakalova A., RA Jacobasch G.; RT "Mutations in the pyruvate kinase L gene in patients with hereditary RT hemolytic anemia."; RL Blood 83:2817-2822(1994). RN [23] RP VARIANTS PKRD GLU-331; ALA-341; LYS-393; SER-393; ASP-458; MET-460 AND RP HIS-498. RX PubMed=7706479; DOI=10.1172/jci117846; RA Baronciani L., Beutler E.; RT "Molecular study of pyruvate kinase deficient patients with hereditary RT nonspherocytic hemolytic anemia."; RL J. Clin. Invest. 95:1702-1709(1995). RN [24] RP VARIANTS PKRD. RA Baronciani L., Westwood B., Beutler E.; RT "Study of the molecular defects in pyruvate kinase (PK) deficient patients RT affected by hereditary nonspherocytic hemolytic anemia (HNHA)."; RL J. Invest. Med. 43:341A-341A(1995). RN [25] RP VARIANT PKHYP GLU-37. RX PubMed=9090535; RX DOI=10.1002/(sici)1098-1004(1997)9:3<282::aid-humu13>3.0.co;2-z; RA Beutler E., Westwood B., van Zwieten R., Roos D.; RT "G-to-T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene RT is the molecular basis of a case of hereditary increase of red blood cell RT ATP."; RL Hum. Mutat. 9:282-285(1997). RN [26] RP VARIANTS PKRD GLN-172; GLN-337; HIS-339; THR-357; ILE-408; THR-431; TRP-486 RP AND GLN-532. RX PubMed=9827908; DOI=10.1046/j.1365-2141.1998.01013.x; RA Zarza R., Alvarez R., Pujades A., Nomdedeu B., Carrera A., Estella J., RA Remacha A., Sanchez J.M., Morey M., Cortes T., Perez Lungmus G., Bureo E., RA Vives Corrons J.L.; RT "Molecular characterization of the PK-LR gene in pyruvate kinase deficient RT Spanish patients."; RL Br. J. Haematol. 103:377-382(1998). RN [27] RP VARIANT PKRD TYR-130. RX PubMed=9886305; DOI=10.1046/j.1365-2141.1998.01094.x; RA Cohen-Solal M., Prehu C., Wajcman H., Poyart C., Bardakdjian-Michau J., RA Kister J., Prome D., Valentin C., Bachir D., Galacteros F.; RT "A new sickle cell disease phenotype associating Hb S trait, severe RT pyruvate kinase deficiency (PK Conakry), and an alpha-2 globin gene variant RT (Hb Conakry)."; RL Br. J. Haematol. 103:950-956(1998). RN [28] RP VARIANTS PKRD SER-332; PRO-337; TRP-486; CYS-498 AND GLN-510. RX PubMed=9482576; RX DOI=10.1002/(sici)1098-1004(1998)11:2<127::aid-humu5>3.0.co;2-g; RA Pastore L., della Morte R., Frisso G., Alfinito F., Vitale D., Calise R.M., RA Ferraro F., Zagari A., Rotoli B., Salvatore F.; RT "Novel mutations and structural implications in R-type pyruvate kinase- RT deficient patients from Southern Italy."; RL Hum. Mutat. 11:127-134(1998). RN [29] RP VARIANTS PKRD MET-335; LYS-348 DEL; GLY-387; ASP-394 AND VAL-394. RX PubMed=11328279; DOI=10.1046/j.1365-2141.2001.02711.x; RA Zanella A., Bianchi P., Fermo E., Iurlo A., Zappa M., Vercellati C., RA Boschetti C., Baronciani L., Cotton F.; RT "Molecular characterization of the PK-LR gene in sixteen pyruvate kinase- RT deficient patients."; RL Br. J. Haematol. 113:43-48(2001). RN [30] RP VARIANTS PKRD TRP-40; 48-THR--THR-53 DEL; PRO-73; ASN-90; ARG-111; THR-154; RP LEU-163; VAL-165; VAL-272; ASN-310; LEU-320; GLU-358 AND PRO-374. RX PubMed=19085939; DOI=10.1002/humu.20915; RA van Wijk R., Huizinga E.G., van Wesel A.C.W., van Oirschot B.A., RA Hadders M.A., van Solinge W.W.; RT "Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) RT deficiency: structural implications of amino acid substitutions in PK."; RL Hum. Mutat. 30:446-453(2009). RN [31] RP VARIANTS PKRD ALA-341 AND GLN-569. RX PubMed=21794208; RA Lyon G.J., Jiang T., Van Wijk R., Wang W., Bodily P.M., Xing J., Tian L., RA Robison R.J., Clement M., Lin Y., Zhang P., Liu Y., Moore B., RA Glessner J.T., Elia J., Reimherr F., van Solinge W.W., Yandell M., RA Hakonarson H., Wang J., Johnson W.E., Wei Z., Wang K.; RT "Exome sequencing and unrelated findings in the context of complex disease RT research: ethical and clinical implications."; RL Discov. Med. 12:41-55(2011). CC -!- FUNCTION: Pyruvate kinase that catalyzes the conversion of CC phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which CC plays a key role in glycolysis. {ECO:0000269|PubMed:11960989}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate; CC Xref=Rhea:RHEA:18157, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58702, ChEBI:CHEBI:456216; CC EC=2.7.1.40; Evidence={ECO:0000269|PubMed:11960989}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18159; CC Evidence={ECO:0000269|PubMed:11960989}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000305|PubMed:11960989}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:11960989}; CC -!- COFACTOR: CC Name=K(+); Xref=ChEBI:CHEBI:29103; CC Evidence={ECO:0000305|PubMed:11960989}; CC -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6- CC bisphosphate. {ECO:0000269|PubMed:11960989}. CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- CC glyceraldehyde 3-phosphate: step 5/5. {ECO:0000269|PubMed:11960989}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11960989}. CC -!- INTERACTION: CC P30613; Q9UBL6-2: CPNE7; NbExp=3; IntAct=EBI-2117450, EBI-12012272; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=R-type; Synonyms=PKR; CC IsoId=P30613-1; Sequence=Displayed; CC Name=L-type; Synonyms=PKL; CC IsoId=P30613-2; Sequence=VSP_002883; CC -!- DISEASE: Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal CC dominant phenotype characterized by increase of red blood cell ATP. CC {ECO:0000269|PubMed:9090535}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A CC frequent cause of hereditary non-spherocytic hemolytic anemia. CC Clinically, pyruvate kinase-deficient patients suffer from a highly CC variable degree of chronic hemolysis, ranging from severe neonatal CC jaundice and fatal anemia at birth, severe transfusion-dependent CC chronic hemolysis, moderate hemolysis with exacerbation during CC infection, to a fully compensated hemolysis without apparent anemia. CC {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, CC ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, CC ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, CC ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, CC ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, CC ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, CC ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, CC ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, CC ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, CC ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, CC ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: L, CC R, M1 and M2. L type is major isozyme in the liver, R is found in red CC cells, M1 is the main form in muscle, heart and brain, and M2 is found CC in early fetal tissues. CC -!- SIMILARITY: Belongs to the pyruvate kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA02515.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pklr/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Pyruvate kinase entry; CC URL="https://en.wikipedia.org/wiki/Pyruvate_kinase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB015983; BAA31706.1; -; mRNA. DR EMBL; M15465; AAA60104.1; -; mRNA. DR EMBL; D13243; BAA02515.1; ALT_SEQ; Genomic_DNA. DR EMBL; AY316591; AAP69527.1; -; Genomic_DNA. DR EMBL; BC025737; AAH25737.1; -; mRNA. DR EMBL; S60712; AAB26262.1; -; mRNA. DR CCDS; CCDS1109.1; -. [P30613-1] DR CCDS; CCDS44240.1; -. [P30613-2] DR PIR; I52269; KIHUPR. DR RefSeq; NP_000289.1; NM_000298.5. [P30613-1] DR RefSeq; NP_870986.1; NM_181871.3. [P30613-2] DR PDB; 2VGB; X-ray; 2.73 A; A/B/C/D=47-574. DR PDB; 2VGF; X-ray; 2.75 A; A/B/C/D=47-574. DR PDB; 2VGG; X-ray; 2.74 A; A/B/C/D=47-574. DR PDB; 2VGI; X-ray; 2.87 A; A/B/C/D=47-574. DR PDB; 4IMA; X-ray; 1.95 A; A/B/C/D=34-574. DR PDB; 4IP7; X-ray; 1.80 A; A/B/C/D=34-574. DR PDB; 5SC8; X-ray; 1.77 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SC9; X-ray; 1.69 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCA; X-ray; 1.92 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCB; X-ray; 1.80 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCC; X-ray; 1.89 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCD; X-ray; 2.04 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCE; X-ray; 2.15 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCF; X-ray; 2.19 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCG; X-ray; 1.94 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCH; X-ray; 2.09 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCI; X-ray; 2.15 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCJ; X-ray; 2.35 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCK; X-ray; 1.72 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SCL; X-ray; 2.13 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 5SDT; X-ray; 1.94 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 6NN4; X-ray; 2.15 A; A/B/C/D=34-574. DR PDB; 6NN5; X-ray; 2.26 A; A/B/C/D=34-574. DR PDB; 6NN7; X-ray; 2.32 A; A/B/C/D/E/F/G/H=34-574. DR PDB; 6NN8; X-ray; 2.42 A; A/B/C/D/E/F/G/H=34-574. DR PDB; 7FRV; X-ray; 2.00 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FRW; X-ray; 1.74 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FRX; X-ray; 1.85 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FRY; X-ray; 1.96 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FRZ; X-ray; 2.08 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS0; X-ray; 2.41 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS1; X-ray; 1.86 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS2; X-ray; 2.37 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS3; X-ray; 1.66 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS4; X-ray; 2.19 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS5; X-ray; 2.18 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS6; X-ray; 2.24 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS7; X-ray; 2.77 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS8; X-ray; 2.10 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FS9; X-ray; 1.72 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FSA; X-ray; 1.91 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FSB; X-ray; 2.50 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FSC; X-ray; 1.85 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7FSD; X-ray; 1.77 A; A/B/C/D/E/F/G/H=34-160, A/B/C/D/E/F/G/H=262-574. DR PDB; 7QDN; X-ray; 1.70 A; A/B/C/D/E/F/G/H=30-574. DR PDB; 7QZU; X-ray; 1.96 A; A/B/C/D/E/F/G/H=30-574. DR PDBsum; 2VGB; -. DR PDBsum; 2VGF; -. DR PDBsum; 2VGG; -. DR PDBsum; 2VGI; -. DR PDBsum; 4IMA; -. DR PDBsum; 4IP7; -. DR PDBsum; 5SC8; -. DR PDBsum; 5SC9; -. DR PDBsum; 5SCA; -. DR PDBsum; 5SCB; -. DR PDBsum; 5SCC; -. DR PDBsum; 5SCD; -. DR PDBsum; 5SCE; -. DR PDBsum; 5SCF; -. DR PDBsum; 5SCG; -. DR PDBsum; 5SCH; -. DR PDBsum; 5SCI; -. DR PDBsum; 5SCJ; -. DR PDBsum; 5SCK; -. DR PDBsum; 5SCL; -. DR PDBsum; 5SDT; -. DR PDBsum; 6NN4; -. DR PDBsum; 6NN5; -. DR PDBsum; 6NN7; -. DR PDBsum; 6NN8; -. DR PDBsum; 7FRV; -. DR PDBsum; 7FRW; -. DR PDBsum; 7FRX; -. DR PDBsum; 7FRY; -. DR PDBsum; 7FRZ; -. DR PDBsum; 7FS0; -. DR PDBsum; 7FS1; -. DR PDBsum; 7FS2; -. DR PDBsum; 7FS3; -. DR PDBsum; 7FS4; -. DR PDBsum; 7FS5; -. DR PDBsum; 7FS6; -. DR PDBsum; 7FS7; -. DR PDBsum; 7FS8; -. DR PDBsum; 7FS9; -. DR PDBsum; 7FSA; -. DR PDBsum; 7FSB; -. DR PDBsum; 7FSC; -. DR PDBsum; 7FSD; -. DR PDBsum; 7QDN; -. DR PDBsum; 7QZU; -. DR AlphaFoldDB; P30613; -. DR SMR; P30613; -. DR BioGRID; 111330; 57. DR ComplexPortal; CPX-3094; PKL pyruvate kinase complex. [P30613-2] DR ComplexPortal; CPX-3095; PKR pyruvate kinase complex. [P30613-1] DR IntAct; P30613; 12. DR STRING; 9606.ENSP00000339933; -. DR BindingDB; P30613; -. DR ChEMBL; CHEMBL1075126; -. DR DrugBank; DB02726; 2-Phosphoglycolic Acid. DR DrugBank; DB00787; Acyclovir. DR DrugBank; DB04551; beta-D-fructofuranose 1,6-bisphosphate. DR DrugBank; DB16236; Mitapivat. DR DrugBank; DB00119; Pyruvic acid. DR GuidetoPHARMACOLOGY; 3007; -. DR GlyGen; P30613; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P30613; -. DR PhosphoSitePlus; P30613; -. DR SwissPalm; P30613; -. DR BioMuta; PKLR; -. DR REPRODUCTION-2DPAGE; P30613; -. DR CPTAC; CPTAC-2748; -. DR EPD; P30613; -. DR jPOST; P30613; -. DR MassIVE; P30613; -. DR MaxQB; P30613; -. DR PaxDb; 9606-ENSP00000339933; -. DR PeptideAtlas; P30613; -. DR ProteomicsDB; 54725; -. [P30613-1] DR ProteomicsDB; 54726; -. [P30613-2] DR Pumba; P30613; -. DR Antibodypedia; 1670; 619 antibodies from 37 providers. DR DNASU; 5313; -. DR Ensembl; ENST00000342741.6; ENSP00000339933.4; ENSG00000143627.19. [P30613-1] DR Ensembl; ENST00000392414.7; ENSP00000376214.3; ENSG00000143627.19. [P30613-2] DR Ensembl; ENST00000571194.5; ENSP00000461487.1; ENSG00000262785.5. [P30613-2] DR Ensembl; ENST00000572740.1; ENSP00000459921.1; ENSG00000262785.5. [P30613-1] DR GeneID; 5313; -. DR KEGG; hsa:5313; -. DR MANE-Select; ENST00000342741.6; ENSP00000339933.4; NM_000298.6; NP_000289.1. DR UCSC; uc001fka.5; human. [P30613-1] DR AGR; HGNC:9020; -. DR CTD; 5313; -. DR DisGeNET; 5313; -. DR GeneCards; PKLR; -. DR HGNC; HGNC:9020; PKLR. DR HPA; ENSG00000143627; Tissue enhanced (bone marrow, kidney, liver). DR MalaCards; PKLR; -. DR MIM; 102900; phenotype. DR MIM; 266200; phenotype. DR MIM; 609712; gene. DR neXtProt; NX_P30613; -. DR OpenTargets; ENSG00000143627; -. DR Orphanet; 766; Hemolytic anemia due to red cell pyruvate kinase deficiency. DR PharmGKB; PA33352; -. DR VEuPathDB; HostDB:ENSG00000143627; -. DR eggNOG; KOG2323; Eukaryota. DR GeneTree; ENSGT00390000008859; -. DR HOGENOM; CLU_015439_0_1_1; -. DR InParanoid; P30613; -. DR OMA; MVRVHHL; -. DR OrthoDB; 312683at2759; -. DR PhylomeDB; P30613; -. DR TreeFam; TF300390; -. DR BioCyc; MetaCyc:HS07088-MONOMER; -. DR BRENDA; 2.7.1.40; 2681. DR PathwayCommons; P30613; -. DR Reactome; R-HSA-163765; ChREBP activates metabolic gene expression. [P30613-1] DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells. [P30613-2] DR Reactome; R-HSA-70171; Glycolysis. DR Reactome; R-HSA-9692914; SARS-CoV-1-host interactions. [P30613-2] DR SABIO-RK; P30613; -. DR SignaLink; P30613; -. DR SIGNOR; P30613; -. DR UniPathway; UPA00109; UER00188. DR BioGRID-ORCS; 5313; 14 hits in 1158 CRISPR screens. DR EvolutionaryTrace; P30613; -. DR GeneWiki; PKLR; -. DR GenomeRNAi; 5313; -. DR Pharos; P30613; Tclin. DR PRO; PR:P30613; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P30613; Protein. DR Bgee; ENSG00000143627; Expressed in liver and 53 other cell types or tissues. DR ExpressionAtlas; P30613; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:1902912; C:pyruvate kinase complex; IDA:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0048029; F:monosaccharide binding; IEA:Ensembl. DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro. DR GO; GO:0004743; F:pyruvate kinase activity; IBA:GO_Central. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IEA:Ensembl. DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central. DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0042866; P:pyruvate biosynthetic process; IEA:Ensembl. DR GO; GO:0033198; P:response to ATP; IEA:Ensembl. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0010038; P:response to metal ion; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR CDD; cd00288; Pyruvate_Kinase; 1. DR Gene3D; 3.20.20.60; Phosphoenolpyruvate-binding domains; 1. DR Gene3D; 2.40.33.10; PK beta-barrel domain-like; 1. DR Gene3D; 3.40.1380.20; Pyruvate kinase, C-terminal domain; 1. DR InterPro; IPR001697; Pyr_Knase. DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom. DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf. DR InterPro; IPR011037; Pyrv_Knase-like_insert_dom_sf. DR InterPro; IPR018209; Pyrv_Knase_AS. DR InterPro; IPR015793; Pyrv_Knase_brl. DR InterPro; IPR015795; Pyrv_Knase_C. DR InterPro; IPR036918; Pyrv_Knase_C_sf. DR InterPro; IPR015806; Pyrv_Knase_insert_dom_sf. DR NCBIfam; TIGR01064; pyruv_kin; 1. DR PANTHER; PTHR11817; PYRUVATE KINASE; 1. DR PANTHER; PTHR11817:SF31; PYRUVATE KINASE PKLR; 1. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR SUPFAM; SSF51621; Phosphoenolpyruvate/pyruvate domain; 1. DR SUPFAM; SSF50800; PK beta-barrel domain-like; 1. DR SUPFAM; SSF52935; PK C-terminal domain-like; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. DR SWISS-2DPAGE; P30613; -. DR Genevisible; P30613; HS. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; KW Disease variant; Glycolysis; Hereditary hemolytic anemia; Kinase; KW Magnesium; Manganese; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Potassium; Pyruvate; Reference proteome; Transferase. FT CHAIN 1..574 FT /note="Pyruvate kinase PKLR" FT /id="PRO_0000112094" FT BINDING 116 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGB" FT BINDING 118..121 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P14618" FT BINDING 118 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 120 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGB" FT BINDING 156 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 157 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 163 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P14618" FT BINDING 250 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P14618" FT BINDING 313 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 315 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 338 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 339 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 339 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 371 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 475..480 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 525 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 532 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT BINDING 559..564 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0007744|PDB:2VGF" FT SITE 313 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P00549" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 292 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..33 FT /note="MSIQENISSLQLRSWVSKSQRDLAKSILIGAPG -> ME (in isoform FT L-type)" FT /evidence="ECO:0000305" FT /id="VSP_002883" FT VARIANT 37 FT /note="G -> E (in PKHYP; dbSNP:rs118204087)" FT /evidence="ECO:0000269|PubMed:9090535" FT /id="VAR_011435" FT VARIANT 40 FT /note="R -> W (in PKRD; dbSNP:rs1484388413)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058467" FT VARIANT 48..53 FT /note="Missing (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058468" FT VARIANT 73 FT /note="L -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058469" FT VARIANT 80 FT /note="S -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:8807089" FT /id="VAR_011436" FT VARIANT 86 FT /note="R -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011437" FT VARIANT 90 FT /note="I -> N (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_011438" FT VARIANT 95 FT /note="G -> R (in PKRD; dbSNP:rs750857114)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011439" FT VARIANT 107 FT /note="M -> T (in PKRD)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004028" FT VARIANT 111 FT /note="G -> R (in PKRD; dbSNP:rs918627824)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_011440" FT VARIANT 115 FT /note="A -> P (in PKRD; Val de Marne)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011441" FT VARIANT 120 FT /note="S -> F (in PKRD; Beaujon)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011442" FT VARIANT 130 FT /note="S -> Y (in PKRD; Conakry; dbSNP:rs118204089)" FT /evidence="ECO:0000269|PubMed:9886305" FT /id="VAR_011443" FT VARIANT 131 FT /note="Missing (in PKRD)" FT /evidence="ECO:0000269|PubMed:8807089" FT /id="VAR_004029" FT VARIANT 134 FT /note="V -> D (in PKRD; dbSNP:rs574051756)" FT /evidence="ECO:0000269|PubMed:8483951" FT /id="VAR_004030" FT VARIANT 153 FT /note="I -> T (in PKRD)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011474" FT VARIANT 154 FT /note="A -> T (in PKRD; dbSNP:rs780192373)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058470" FT VARIANT 155 FT /note="L -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:8483951" FT /id="VAR_004031" FT VARIANT 159 FT /note="G -> V (in PKRD; dbSNP:rs1239029841)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011444" FT VARIANT 163 FT /note="R -> C (in PKRD; Linz; dbSNP:rs118204083)" FT /evidence="ECO:0000269|PubMed:2018831" FT /id="VAR_004033" FT VARIANT 163 FT /note="R -> L (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058471" FT VARIANT 165 FT /note="G -> V (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058472" FT VARIANT 172 FT /note="E -> Q (in PKRD; Sassari; dbSNP:rs757359024)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004032" FT VARIANT 219 FT /note="I -> T (in PKRD; dbSNP:rs200572803)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011475" FT VARIANT 221 FT /note="D -> DD (in PKRD)" FT /evidence="ECO:0000269|PubMed:8807089" FT /id="VAR_004034" FT VARIANT 222 FT /note="G -> A (in PKRD; Katsushika)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011445" FT VARIANT 263 FT /note="G -> R (in PKRD; dbSNP:rs1253386414)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011447" FT VARIANT 263 FT /note="G -> W (in PKRD)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011448" FT VARIANT 272 FT /note="L -> V (in PKRD; dbSNP:rs147659527)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058473" FT VARIANT 275 FT /note="G -> R (in PKRD; dbSNP:rs747549978)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004035" FT VARIANT 281 FT /note="D -> N (in PKRD)" FT /evidence="ECO:0000269|PubMed:8807089" FT /id="VAR_004036" FT VARIANT 287 FT /note="F -> V (in PKRD)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004037" FT VARIANT 288 FT /note="V -> L (in PKRD; Moriguchi)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011449" FT VARIANT 293 FT /note="D -> N (in PKRD; dbSNP:rs1352610988)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011446" FT VARIANT 295 FT /note="A -> V (in PKRD; dbSNP:rs766353400)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011450" FT VARIANT 310 FT /note="I -> N (in PKRD; Dordrecht)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_011451" FT VARIANT 314 FT /note="I -> T (in PKRD; Hong Kong; dbSNP:rs981505482)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004038" FT VARIANT 315 FT /note="E -> K (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011452" FT VARIANT 320 FT /note="V -> L (in PKRD; dbSNP:rs549295725)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058474" FT VARIANT 331 FT /note="D -> E (in PKRD; Parma; dbSNP:rs138476691)" FT /evidence="ECO:0000269|PubMed:7706479" FT /id="VAR_004039" FT VARIANT 331 FT /note="D -> N (in PKRD; dbSNP:rs773893686)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011453" FT VARIANT 332 FT /note="G -> S (in PKRD; loss of catalytical activity; FT dbSNP:rs773626254)" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:9482576" FT /id="VAR_004040" FT VARIANT 335 FT /note="V -> M (in PKRD)" FT /evidence="ECO:0000269|PubMed:11328279" FT /id="VAR_011476" FT VARIANT 336 FT /note="A -> S (in PKRD)" FT /evidence="ECO:0000269|PubMed:8180378" FT /id="VAR_004041" FT VARIANT 337 FT /note="R -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:9482576" FT /id="VAR_004042" FT VARIANT 337 FT /note="R -> Q (in PKRD; dbSNP:rs1167329263)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004043" FT VARIANT 339 FT /note="D -> H (in PKRD; dbSNP:rs747097960)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004044" FT VARIANT 341 FT /note="G -> A (in PKRD; dbSNP:rs1227427396)" FT /evidence="ECO:0000269|PubMed:21794208, FT ECO:0000269|PubMed:7706479" FT /id="VAR_004045" FT VARIANT 341 FT /note="G -> D (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011454" FT VARIANT 342 FT /note="I -> F (in PKRD)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011455" FT VARIANT 348 FT /note="K -> N (in PKRD; Kamata)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011456" FT VARIANT 348 FT /note="Missing (in PKRD; Brescia)" FT /evidence="ECO:0000269|PubMed:11328279" FT /id="VAR_011457" FT VARIANT 352 FT /note="A -> D (in PKRD; dbSNP:rs1240481888)" FT /evidence="ECO:0000269|PubMed:10772876, FT ECO:0000269|PubMed:9075576" FT /id="VAR_011477" FT VARIANT 354 FT /note="Missing (in PKRD)" FT /evidence="ECO:0000269|PubMed:8180378" FT /id="VAR_004046" FT VARIANT 357 FT /note="I -> T (in PKRD; dbSNP:rs779152555)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004047" FT VARIANT 358 FT /note="G -> E (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058475" FT VARIANT 359 FT /note="R -> C (in PKRD; Aomori; dbSNP:rs138871700)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004048" FT VARIANT 359 FT /note="R -> H (in PKRD; dbSNP:rs1376070580)" FT /evidence="ECO:0000269|PubMed:8483951" FT /id="VAR_004049" FT VARIANT 361 FT /note="N -> D (in PKRD; dbSNP:rs765903674)" FT /evidence="ECO:0000269|PubMed:8180378" FT /id="VAR_004050" FT VARIANT 364 FT /note="G -> D (in PKRD; Tjaereborg; unstability of the FT protein and decrease in catalytic activity; FT dbSNP:rs981579065)" FT /evidence="ECO:0000269|PubMed:11960989" FT /id="VAR_011458" FT VARIANT 368 FT /note="V -> F (in PKRD; Osaka)" FT /evidence="ECO:0000269|PubMed:8476433" FT /id="VAR_004051" FT VARIANT 374 FT /note="L -> P (in PKRD)" FT /evidence="ECO:0000269|PubMed:19085939" FT /id="VAR_058476" FT VARIANT 376 FT /note="S -> I (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011459" FT VARIANT 384 FT /note="T -> M (in PKRD; Tokyo/Beirut; no conformational FT change; dbSNP:rs74315362)" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:2018831" FT /id="VAR_004052" FT VARIANT 385 FT /note="R -> W (in PKRD)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011478" FT VARIANT 387 FT /note="E -> G (in PKRD)" FT /evidence="ECO:0000269|PubMed:11328279" FT /id="VAR_011460" FT VARIANT 390 FT /note="D -> N (in PKRD; Mantova; almost complete FT inactivation; dbSNP:rs147034239)" FT /evidence="ECO:0000269|PubMed:11960989" FT /id="VAR_011461" FT VARIANT 392 FT /note="A -> T (in PKRD; dbSNP:rs1403323591)" FT /evidence="ECO:0000269|PubMed:8180378" FT /id="VAR_004053" FT VARIANT 393 FT /note="N -> K (in PKRD; dbSNP:rs1168490341)" FT /evidence="ECO:0000269|PubMed:7706479" FT /id="VAR_004054" FT VARIANT 393 FT /note="N -> S (in PKRD; Paris; dbSNP:rs776594413)" FT /evidence="ECO:0000269|PubMed:7706479" FT /id="VAR_004055" FT VARIANT 394 FT /note="A -> D (in PKRD; dbSNP:rs1035640530)" FT /evidence="ECO:0000269|PubMed:11328279" FT /id="VAR_011462" FT VARIANT 394 FT /note="A -> V (in PKRD)" FT /evidence="ECO:0000269|PubMed:11328279" FT /id="VAR_011463" FT VARIANT 401 FT /note="C -> CS (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_004056" FT VARIANT 408 FT /note="T -> A (in PKRD; Hirosaki)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011464" FT VARIANT 408 FT /note="T -> I (in PKRD)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004057" FT VARIANT 421 FT /note="Q -> K (in PKRD; Fukushima/Maebashi/Sendai; FT dbSNP:rs118204084)" FT /evidence="ECO:0000269|PubMed:1536957" FT /id="VAR_004058" FT VARIANT 426 FT /note="R -> Q (in PKRD; Sapporo; dbSNP:rs768002493)" FT /evidence="ECO:0000269|PubMed:8481523" FT /id="VAR_004059" FT VARIANT 426 FT /note="R -> W (in PKRD; Naniwa; dbSNP:rs1023689443)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004060" FT VARIANT 427 FT /note="E -> A (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011465" FT VARIANT 427 FT /note="E -> D (in PKRD)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011466" FT VARIANT 431 FT /note="A -> T (in PKRD; dbSNP:rs762591322)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004061" FT VARIANT 458 FT /note="G -> D (in PKRD; dbSNP:rs755522396)" FT /evidence="ECO:0000269|PubMed:7706479" FT /id="VAR_004062" FT VARIANT 459 FT /note="A -> V (in PKRD)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004063" FT VARIANT 460 FT /note="V -> M (in PKRD; dbSNP:rs752034960)" FT /evidence="ECO:0000269|PubMed:7706479" FT /id="VAR_004064" FT VARIANT 468 FT /note="A -> G (in PKRD; dbSNP:rs750540943)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011479" FT VARIANT 468 FT /note="A -> V (in PKRD; Hadano)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004065" FT VARIANT 477 FT /note="T -> A (in PKRD; dbSNP:rs759466273)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011467" FT VARIANT 479 FT /note="R -> H (in PKRD; Amish; no conformational change; FT dbSNP:rs118204085)" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0000269|PubMed:8161798" FT /id="VAR_011480" FT VARIANT 485 FT /note="S -> F (in PKRD)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011468" FT VARIANT 486 FT /note="R -> W (in PKRD; no conformational change; FT dbSNP:rs116100695)" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:9482576, FT ECO:0000269|PubMed:9827908" FT /id="VAR_004066" FT VARIANT 488 FT /note="R -> Q (in PKRD; dbSNP:rs369183199)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011469" FT VARIANT 490 FT /note="R -> W (in PKRD; dbSNP:rs200133000)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004067" FT VARIANT 495 FT /note="A -> T (in PKRD)" FT /evidence="ECO:0000269|PubMed:9075576" FT /id="VAR_011470" FT VARIANT 495 FT /note="A -> V (in PKRD; dbSNP:rs141560532)" FT /evidence="ECO:0000269|PubMed:8483951" FT /id="VAR_004068" FT VARIANT 498 FT /note="R -> C (in PKRD; dbSNP:rs551883218)" FT /evidence="ECO:0000269|PubMed:9482576" FT /id="VAR_004069" FT VARIANT 498 FT /note="R -> H (in PKRD; dbSNP:rs758327704)" FT /evidence="ECO:0000269|PubMed:7706479, FT ECO:0000269|PubMed:8180378" FT /id="VAR_004070" FT VARIANT 504 FT /note="R -> L (in PKRD; instability of the protein; FT dbSNP:rs185753709)" FT /evidence="ECO:0000269|PubMed:11960989" FT /id="VAR_011471" FT VARIANT 506 FT /note="V -> I (in dbSNP:rs8177988)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_018848" FT VARIANT 510 FT /note="R -> Q (in PKRD; dbSNP:rs113403872)" FT /evidence="ECO:0000269|PubMed:8180378, FT ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:9482576" FT /id="VAR_004071" FT VARIANT 511 FT /note="G -> R (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011472" FT VARIANT 531 FT /note="R -> C (in PKRD)" FT /evidence="ECO:0000269|PubMed:10087985" FT /id="VAR_011473" FT VARIANT 532 FT /note="R -> Q (in PKRD; dbSNP:rs758278200)" FT /evidence="ECO:0000269|PubMed:9827908" FT /id="VAR_004072" FT VARIANT 532 FT /note="R -> W (in PKRD; Complete loss in the responsiveness FT to fructose 1,6-bisphosphate, FBP; dbSNP:rs201255024)" FT /evidence="ECO:0000269|PubMed:11960989, FT ECO:0000269|PubMed:8180378" FT /id="VAR_004073" FT VARIANT 552 FT /note="V -> M (in PKRD; dbSNP:rs370316462)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004074" FT VARIANT 557 FT /note="G -> A (in PKRD)" FT /evidence="ECO:0000269|PubMed:10772876" FT /id="VAR_011481" FT VARIANT 559 FT /note="R -> G (in PKRD)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004075" FT VARIANT 566 FT /note="N -> K (in PKRD)" FT /evidence="ECO:0000269|PubMed:8664896" FT /id="VAR_004076" FT VARIANT 569 FT /note="R -> Q (in PKRD; dbSNP:rs61755431)" FT /evidence="ECO:0000269|PubMed:21794208" FT /id="VAR_011482" FT CONFLICT 381 FT /note="P -> A (in Ref. 3; BAA02515)" FT /evidence="ECO:0000305" FT CONFLICT 423 FT /note="A -> R (in Ref. 2; AAA60104)" FT /evidence="ECO:0000305" FT TURN 42..44 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 45..51 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 61..64 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 69..75 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 88..93 FT /evidence="ECO:0007829|PDB:7FS3" FT TURN 96..98 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 101..110 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 112..118 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 124..139 FT /evidence="ECO:0007829|PDB:7FS3" FT TURN 140..143 FT /evidence="ECO:0007829|PDB:7FS3" FT TURN 145..147 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:2VGB" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 182..186 FT /evidence="ECO:0007829|PDB:4IP7" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 199..203 FT /evidence="ECO:0007829|PDB:4IP7" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 216..219 FT /evidence="ECO:0007829|PDB:4IP7" FT TURN 220..223 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 224..232 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 235..242 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:4IP7" FT STRAND 251..253 FT /evidence="ECO:0007829|PDB:4IP7" FT HELIX 266..277 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 281..285 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 291..301 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 308..314 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 317..321 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 323..329 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 330..336 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 337..343 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 346..348 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 349..363 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 375..378 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:7FRZ" FT HELIX 385..397 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 400..405 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 406..409 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 414..430 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 434..444 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 451..466 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 469..474 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 479..485 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 490..498 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 500..505 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 506..508 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 512..516 FT /evidence="ECO:0007829|PDB:7FS3" FT HELIX 525..542 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 551..561 FT /evidence="ECO:0007829|PDB:7FS3" FT STRAND 565..572 FT /evidence="ECO:0007829|PDB:7FS3" SQ SEQUENCE 574 AA; 61830 MW; 3B430896832032F5 CRC64; MSIQENISSL QLRSWVSKSQ RDLAKSILIG APGGPAGYLR RASVAQLTQE LGTAFFQQQQ LPAAMADTFL EHLCLLDIDS EPVAARSTSI IATIGPASRS VERLKEMIKA GMNIARLNFS HGSHEYHAES IANVREAVES FAGSPLSYRP VAIALDTKGP EIRTGILQGG PESEVELVKG SQVLVTVDPA FRTRGNANTV WVDYPNIVRV VPVGGRIYID DGLISLVVQK IGPEGLVTQV ENGGVLGSRK GVNLPGAQVD LPGLSEQDVR DLRFGVEHGV DIVFASFVRK ASDVAAVRAA LGPEGHGIKI ISKIENHEGV KRFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC NLAGKPVVCA TQMLESMITK PRPTRAETSD VANAVLDGAD CIMLSGETAK GNFPVEAVKM QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EAAFKCCAAA IIVLTTTGRS AQLLSRYRPR AAVIAVTRSA QAARQVHLCR GVFPLLYREP PEAIWADDVD RRVQFGIESG KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSIS //