KPYR_HUMAN
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 03-AUG-2022, entry version 242.
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 ON VARIANTS.
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 ON VARIANTS.
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 ON VARIANTS.
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 ON VARIANTS.
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 ON VARIANTS.
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: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:9482576,
CC ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305,
CC ECO:0000269|Ref.24}. Note=The disease is caused by variants affecting
CC 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";
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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; 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; 7QDN; X-ray; 1.70 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; 6NN4; -.
DR PDBsum; 6NN5; -.
DR PDBsum; 6NN7; -.
DR PDBsum; 6NN8; -.
DR PDBsum; 7QDN; -.
DR AlphaFoldDB; P30613; -.
DR SMR; P30613; -.
DR BioGRID; 111330; 49.
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; DB00119; Pyruvic acid.
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 SWISS-2DPAGE; P30613; -.
DR EPD; P30613; -.
DR jPOST; P30613; -.
DR MassIVE; P30613; -.
DR MaxQB; P30613; -.
DR PaxDb; P30613; -.
DR PeptideAtlas; P30613; -.
DR PRIDE; P30613; -.
DR ProteomicsDB; 54725; -. [P30613-1]
DR ProteomicsDB; 54726; -. [P30613-2]
DR Antibodypedia; 1670; 555 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 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; 933620at2759; -.
DR PhylomeDB; P30613; -.
DR TreeFam; TF300390; -.
DR BioCyc; MetaCyc:HS07088-MON; -.
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 SABIO-RK; P30613; -.
DR SignaLink; P30613; -.
DR SIGNOR; P30613; -.
DR UniPathway; UPA00109; UER00188.
DR BioGRID-ORCS; 5313; 14 hits in 1079 CRISPR screens.
DR EvolutionaryTrace; P30613; -.
DR GeneWiki; PKLR; -.
DR GenomeRNAi; 5313; -.
DR Pharos; P30613; Tbio.
DR PRO; PR:P30613; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P30613; protein.
DR Bgee; ENSG00000143627; Expressed in liver and 52 other tissues.
DR ExpressionAtlas; P30613; baseline and differential.
DR Genevisible; P30613; HS.
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: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:0030955; F:potassium ion binding; IEA:InterPro.
DR GO; GO:0004743; F:pyruvate kinase activity; IBA:GO_Central.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:Ensembl.
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: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:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR CDD; cd00288; Pyruvate_Kinase; 1.
DR Gene3D; 2.40.33.10; -; 1.
DR Gene3D; 3.20.20.60; -; 1.
DR Gene3D; 3.40.1380.20; -; 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 PANTHER; PTHR11817; PTHR11817; 1.
DR Pfam; PF00224; PK; 1.
DR Pfam; PF02887; PK_C; 1.
DR PRINTS; PR01050; PYRUVTKNASE.
DR SUPFAM; SSF50800; SSF50800; 1.
DR SUPFAM; SSF51621; SSF51621; 1.
DR SUPFAM; SSF52935; SSF52935; 1.
DR TIGRFAMs; TIGR01064; pyruv_kin; 1.
DR PROSITE; PS00110; PYRUVATE_KINASE; 1.
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 /id="VAR_011436"
FT VARIANT 86
FT /note="R -> P (in PKRD)"
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 /id="VAR_011439"
FT VARIANT 107
FT /note="M -> T (in PKRD)"
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 /id="VAR_011441"
FT VARIANT 120
FT /note="S -> F (in PKRD; Beaujon)"
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 /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 /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 /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 /id="VAR_011475"
FT VARIANT 221
FT /note="D -> DD (in PKRD)"
FT /id="VAR_004034"
FT VARIANT 222
FT /note="G -> A (in PKRD; Katsushika)"
FT /id="VAR_011445"
FT VARIANT 263
FT /note="G -> R (in PKRD; dbSNP:rs1253386414)"
FT /id="VAR_011447"
FT VARIANT 263
FT /note="G -> W (in PKRD)"
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 /id="VAR_004035"
FT VARIANT 281
FT /note="D -> N (in PKRD)"
FT /id="VAR_004036"
FT VARIANT 287
FT /note="F -> V (in PKRD)"
FT /id="VAR_004037"
FT VARIANT 288
FT /note="V -> L (in PKRD; Moriguchi)"
FT /id="VAR_011449"
FT VARIANT 293
FT /note="D -> N (in PKRD; dbSNP:rs1352610988)"
FT /id="VAR_011446"
FT VARIANT 295
FT /note="A -> V (in PKRD; dbSNP:rs766353400)"
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 /id="VAR_004038"
FT VARIANT 315
FT /note="E -> K (in PKRD)"
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 /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 /id="VAR_011454"
FT VARIANT 342
FT /note="I -> F (in PKRD)"
FT /id="VAR_011455"
FT VARIANT 348
FT /note="K -> N (in PKRD; Kamata)"
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 /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 /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 /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 /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 /id="VAR_004056"
FT VARIANT 408
FT /note="T -> A (in PKRD; Hirosaki)"
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 /id="VAR_004060"
FT VARIANT 427
FT /note="E -> A (in PKRD)"
FT /id="VAR_011465"
FT VARIANT 427
FT /note="E -> D (in PKRD)"
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 /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 /id="VAR_011479"
FT VARIANT 468
FT /note="A -> V (in PKRD; Hadano)"
FT /id="VAR_004065"
FT VARIANT 477
FT /note="T -> A (in PKRD; dbSNP:rs759466273)"
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 /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 /id="VAR_011469"
FT VARIANT 490
FT /note="R -> W (in PKRD; dbSNP:rs200133000)"
FT /id="VAR_004067"
FT VARIANT 495
FT /note="A -> T (in PKRD)"
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 /id="VAR_011472"
FT VARIANT 531
FT /note="R -> C (in PKRD)"
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 /id="VAR_004074"
FT VARIANT 557
FT /note="G -> A (in PKRD)"
FT /id="VAR_011481"
FT VARIANT 559
FT /note="R -> G (in PKRD)"
FT /id="VAR_004075"
FT VARIANT 566
FT /note="N -> K (in PKRD)"
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 HELIX 45..48
FT /evidence="ECO:0007829|PDB:6NN8"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:4IMA"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:4IMA"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 69..74
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:4IP7"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 101..110
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 124..139
FT /evidence="ECO:0007829|PDB:4IP7"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:6NN7"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:4IP7"
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:4IP7"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 291..301
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 317..321
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 323..329
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 337..343
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 349..363
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 367..372
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 385..397
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 400..405
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 406..409
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 414..430
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 434..442
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 451..466
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 469..474
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 479..485
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 490..498
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 500..505
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 512..516
FT /evidence="ECO:0007829|PDB:4IP7"
FT HELIX 525..542
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 551..561
FT /evidence="ECO:0007829|PDB:4IP7"
FT STRAND 565..572
FT /evidence="ECO:0007829|PDB:4IP7"
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
