LOCUS       NM_000298               3047 bp    mRNA    linear   PRI 14-OCT-2024
DEFINITION  Homo sapiens pyruvate kinase L/R (PKLR), transcript variant 1,
            mRNA.
ACCESSION   NM_000298
VERSION     NM_000298.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3047)
  AUTHORS   Maciak,K., Jurkiewicz,A., Strojny,W., Adamowicz-Salach,A.,
            Romiszewska,M., Jackowska,T., Kwiecinska,K., Poznanski,J., Gora,M.
            and Burzynska,B.
  TITLE     PKLR mutations in pyruvate kinase deficient Polish patients:
            Functional characteristics of c.101-1G > A and c.1058delAAG
            variants
  JOURNAL   Blood Cells Mol Dis 107, 102841 (2024)
   PUBMED   38581917
  REMARK    GeneRIF: PKLR mutations in pyruvate kinase deficient Polish
            patients: Functional characteristics of c.101-1G > A and
            c.1058delAAG variants.
REFERENCE   2  (bases 1 to 3047)
  AUTHORS   Chen,W.Y., Thuy Dung,P.V., Yeh,H.L., Chen,W.H., Jiang,K.C.,
            Li,H.R., Chen,Z.Q., Hsiao,M., Huang,J., Wen,Y.C. and Liu,Y.N.
  TITLE     Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine
            differentiation of castration-resistant prostate cancer
  JOURNAL   Redox Biol 62, 102686 (2023)
   PUBMED   36963289
  REMARK    GeneRIF: Targeting PKLR/MYCN/ROMO1 signaling suppresses
            neuroendocrine differentiation of castration-resistant prostate
            cancer.
REFERENCE   3  (bases 1 to 3047)
  AUTHORS   Dongerdiye,R., Bokde,M., More,T.A., Saptarshi,A., Devendra,R.,
            Chiddarwar,A., Warang,P. and Kedar,P.
  TITLE     Targeted next-generation sequencing identifies eighteen novel
            mutations expanding the molecular and clinical spectrum of PKLR
            gene disorders in the Indian population
  JOURNAL   Ann Hematol 102 (5), 1029-1036 (2023)
   PUBMED   36892591
  REMARK    GeneRIF: Targeted next-generation sequencing identifies eighteen
            novel mutations expanding the molecular and clinical spectrum of
            PKLR gene disorders in the Indian population.
REFERENCE   4  (bases 1 to 3047)
  AUTHORS   Sheng,D., Chen,B., Wang,C., Xiao,X., Hu,A., Liu,W., Kuang,Y.,
            Sample,K.M., Zacksenhaus,E., Gajendran,B., Pan,W. and Ben-David,Y.
  TITLE     FLI1 accelerates leukemogenesis through transcriptional regulation
            of pyruvate kinase-L/R and other glycolytic genes
  JOURNAL   Med Oncol 40 (2), 69 (2022)
   PUBMED   36586017
  REMARK    GeneRIF: FLI1 accelerates leukemogenesis through transcriptional
            regulation of pyruvate kinase-L/R and other glycolytic genes.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3047)
  AUTHORS   Mungkalasut,P., Kiatamornrak,P., Jugnam-Ang,W., Krudsood,S.,
            Cheepsunthorn,P. and Cheepsunthorn,C.L.
  TITLE     Haematological profile of malaria patients with G6PD and PKLR
            variants (erythrocytic enzymopathies): a cross-sectional study in
            Thailand
  JOURNAL   Malar J 21 (1), 250 (2022)
   PUBMED   36038921
  REMARK    GeneRIF: Haematological profile of malaria patients with G6PD and
            PKLR variants (erythrocytic enzymopathies): a cross-sectional study
            in Thailand.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3047)
  AUTHORS   Zanella,A., Fermo,E., Bianchi,P., Chiarelli,L.R. and Valentini,G.
  TITLE     Pyruvate kinase deficiency: the genotype-phenotype association
  JOURNAL   Blood Rev 21 (4), 217-231 (2007)
   PUBMED   17360088
  REMARK    GeneRIF: genotype-phenotype association in pyruvate kinase
            deficiency [review]
            Review article
REFERENCE   7  (bases 1 to 3047)
  AUTHORS   Kanno,H., Fujii,H. and Miwa,S.
  TITLE     Structural analysis of human pyruvate kinase L-gene and
            identification of the promoter activity in erythroid cells
  JOURNAL   Biochem Biophys Res Commun 188 (2), 516-523 (1992)
   PUBMED   1445295
REFERENCE   8  (bases 1 to 3047)
  AUTHORS   Dawson,S.J. and White,L.A.
  TITLE     Treatment of Haemophilus aphrophilus endocarditis with
            ciprofloxacin
  JOURNAL   J Infect 24 (3), 317-320 (1992)
   PUBMED   1602151
REFERENCE   9  (bases 1 to 3047)
  AUTHORS   Kanno,H., Fujii,H., Hirono,A., Omine,M. and Miwa,S.
  TITLE     Identical point mutations of the R-type pyruvate kinase (PK) cDNA
            found in unrelated PK variants associated with hereditary hemolytic
            anemia
  JOURNAL   Blood 79 (5), 1347-1350 (1992)
   PUBMED   1536957
REFERENCE   10 (bases 1 to 3047)
  AUTHORS   Kanno,H., Fujii,H., Hirono,A. and Miwa,S.
  TITLE     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
  JOURNAL   Proc Natl Acad Sci U S A 88 (18), 8218-8221 (1991)
   PUBMED   1896471
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL713999.28, BC025737.1 and
            H77542.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 10, 2018 this sequence version replaced NM_000298.5.
            
            Summary: The protein encoded by this gene is a pyruvate kinase that
            catalyzes the transphosphorylation of phohsphoenolpyruvate into
            pyruvate and ATP, which is the rate-limiting step of glycolysis.
            Defects in this enzyme, due to gene mutations or genetic
            variations, are the common cause of chronic hereditary
            nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple
            transcript variants encoding different isoforms have been found for
            this gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1). Isoform 1 is also known as type R.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The extent of this transcript is
            supported by transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC025737.1, AB015983.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1968968, SAMEA1970526
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG   :: community standard
                                                  (PMID:17360088)
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000342741.6/
                                                  ENSP00000339933.4
            RefSeq Select criteria             :: based on conservation,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-18                AL713999.28        129701-129718       c
            19-1747             BC025737.1         1-1729
            1748-3041           AL713999.28        117579-118872       c
            3042-3047           H77542.1           36-41               c
FEATURES             Location/Qualifiers
     source          1..3047
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q22"
     gene            1..3047
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /note="pyruvate kinase L/R"
                     /db_xref="GeneID:5313"
                     /db_xref="HGNC:HGNC:9020"
                     /db_xref="MIM:609712"
     exon            1..143
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     CDS             44..1768
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /EC_number="2.7.1.40"
                     /note="isoform 1 is encoded by transcript variant 1;
                     pyruvate kinase type L; pyruvate kinase, liver and blood
                     cell; pyruvate kinase 1; pyruvate kinase isozyme R/L;
                     R-type/L-type pyruvate kinase; red cell/liver pyruvate
                     kinase; pyruvate kinase isozymes R/L; pyruvate kinase
                     isozymes L/R; pyruvate kinase PKLR; pyruvate kinase, liver
                     and RBC"
                     /codon_start=1
                     /product="pyruvate kinase PKLR isoform 1"
                     /protein_id="NP_000289.1"
                     /db_xref="CCDS:CCDS1109.1"
                     /db_xref="GeneID:5313"
                     /db_xref="HGNC:HGNC:9020"
                     /db_xref="MIM:609712"
                     /translation="MSIQENISSLQLRSWVSKSQRDLAKSILIGAPGGPAGYLRRASV
                     AQLTQELGTAFFQQQQLPAAMADTFLEHLCLLDIDSEPVAARSTSIIATIGPASRSVE
                     RLKEMIKAGMNIARLNFSHGSHEYHAESIANVREAVESFAGSPLSYRPVAIALDTKGP
                     EIRTGILQGGPESEVELVKGSQVLVTVDPAFRTRGNANTVWVDYPNIVRVVPVGGRIY
                     IDDGLISLVVQKIGPEGLVTQVENGGVLGSRKGVNLPGAQVDLPGLSEQDVRDLRFGV
                     EHGVDIVFASFVRKASDVAAVRAALGPEGHGIKIISKIENHEGVKRFDEILEVSDGIM
                     VARGDLGIEIPAEKVFLAQKMMIGRCNLAGKPVVCATQMLESMITKPRPTRAETSDVA
                     NAVLDGADCIMLSGETAKGNFPVEAVKMQHAIAREAEAAVYHRQLFEELRRAAPLSRD
                     PTEVTAIGAVEAAFKCCAAAIIVLTTTGRSAQLLSRYRPRAAVIAVTRSAQAARQVHL
                     CRGVFPLLYREPPEAIWADDVDRRVQFGIESGKLRGFLRVGDLVIVVTGWRPGSGYTN
                     IMRVLSIS"
     exon            144..326
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            327..418
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            419..550
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            551..737
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            738..1008
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            1009..1159
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            1160..1312
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            1313..1479
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            1480..1661
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     exon            1662..3047
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      2087
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /note="major polyA site"
     polyA_site      2491
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /note="major polyA site"
     regulatory      3028..3033
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
                     /note="hexamer: AATACA"
     polyA_site      3047
                     /gene="PKLR"
                     /gene_synonym="CNSHA2; PK1; PKL; PKRL; RPK"
ORIGIN      
        1 ctctcattcc atggtcccgc agccccaggc ccacactgaa agcatgtcga tccaggagaa
       61 catatcatcc ctgcagcttc ggtcatgggt ctctaagtcc caaagagact tagcaaagtc
      121 catcctgatt ggggctccag gagggccagc ggggtatctg cggcgggcca gtgtggccca
      181 actgacccag gagctgggca ctgccttctt ccagcagcag cagctgccag ctgctatggc
      241 agacaccttc ctggaacacc tctgcctact ggacattgac tccgagcccg tggctgctcg
      301 cagtaccagc atcattgcca ccatcgggcc agcatctcgc tccgtggagc gcctcaagga
      361 gatgatcaag gccgggatga acattgcgcg actcaacttc tcccacggct cccacgagta
      421 ccatgctgag tccatcgcca acgtccggga ggcggtggag agctttgcag gttccccact
      481 cagctaccgg cccgtggcca tcgccctgga caccaaggga ccggagatcc gcactgggat
      541 cctgcagggg ggtccagagt cggaagtgga gctggtgaag ggctcccagg tgctggtgac
      601 tgtggacccc gcgttccgga cgcgggggaa cgcgaacacc gtgtgggtgg actaccccaa
      661 tattgtccgg gtcgtgccgg tggggggccg catctacatt gacgacgggc tcatctccct
      721 agtggtccag aaaatcggcc cagagggact ggtgacccaa gtggagaacg gcggcgtcct
      781 gggcagccgg aagggcgtga acttgccagg ggcccaggtg gacttgcccg ggctgtccga
      841 gcaggacgtc cgagacctgc gcttcggggt ggagcatggg gtggacatcg tctttgcctc
      901 ctttgtgcgg aaagccagcg acgtggctgc cgtcagggct gctctgggtc cggaaggaca
      961 cggcatcaag atcatcagca aaattgagaa ccacgaaggc gtgaagaggt ttgatgaaat
     1021 cctggaggtg agcgacggca tcatggtggc acggggggac ctaggcatcg agatcccagc
     1081 agagaaggtt ttcctggctc agaagatgat gattgggcgc tgcaacttgg cgggcaagcc
     1141 tgttgtctgt gccacacaga tgctggagag catgattacc aagccccggc caacgagggc
     1201 agagacaagc gatgtcgcca atgctgtgct ggatggggct gactgcatca tgctgtcagg
     1261 ggagactgcc aagggcaact tccctgtgga agcggtgaag atgcagcatg cgattgcccg
     1321 ggaggcagag gccgcagtgt accaccggca gctgtttgag gagctacgtc gggcagcgcc
     1381 actaagccgt gatcccactg aggtcaccgc cattggtgct gtggaggctg ccttcaagtg
     1441 ctgtgctgct gccatcattg tgctgaccac aactggccgc tcagcccagc ttctgtctcg
     1501 gtaccgacct cgggcagcag tcattgctgt cacccgctct gcccaggctg cccgccaggt
     1561 ccacttatgc cgaggagtct tccccttgct ttaccgtgaa cctccagaag ccatctgggc
     1621 agatgatgta gatcgccggg tgcaatttgg cattgaaagt ggaaagctcc gtggcttcct
     1681 ccgtgttgga gacctggtga ttgtggtgac aggctggcga cctggctccg gctacaccaa
     1741 catcatgcgg gtgctaagca tatcctgaga cgcccctccc tcctctggcc cagcctaccc
     1801 ttgtacccca tcccttcctc cccagtctac gttctccagc ccacacccct ccaaagcccc
     1861 acctttaagt cctctcttct ctattcctga ccctccctac ctgaggccta tctgagacta
     1921 taactgtcat ctagcccctt cgaggttgcc ccttccccat ctccatttca cacaggtcct
     1981 gaaagtctgt gtccaattat gcactggcca cccaacagca ccaattgtac attccctgca
     2041 tccaatctgc tcagcaggcc ctaagatgcc ttgagtcttt aatcccagtt tggctggtta
     2101 attccataac cccaggcatc ccatcccttg gggtggggga gaggggagac agggcaatct
     2161 tgtccacagt ctcccattct catatgtagc cctcatgata atctgggcat ctcgtgccag
     2221 ggcaggctac cccttcatgg tgactaacag ttacatgaaa gtccacgctt ttgggaaaac
     2281 tgggtgggat ggatgctggg gagaagtgag ggctgggcag ctgattttgt cactgtcttc
     2341 acaacctccg tgctgggctt gtagaccact gtcctggctg ctctcatgcc tgcctgatac
     2401 cctgcttggt caaatccccg gctgcttcct tctgcaccca gaaattcctt cccactcatg
     2461 ttgttcccac acacaaacca agagccaaaa atgagtgtgt ctattttata tttaaaccca
     2521 gctgtttgga agcaattata aaacttctcc cacacaccaa gaaccccaga actccccacc
     2581 cagaaggaaa ggagacttag ggtcctggtc ccacagtctt taatgctgta gagtaggaga
     2641 ggggacaggc agagtgaggg tggtaaagga ctactcttgt ccctgagaag gcagaggtgc
     2701 tggctggcct gcccttcccc aggcttggat accttgggcc tttcccttat tcctgcacca
     2761 acagcaaact cagaaggaaa aaacaaaaca aaactctaaa ggtaaacgcg gtccttctcc
     2821 ctctctcatg tggctcctcc tgcccctacc tgggagaagg ttcaagtatt gcgctgatgg
     2881 gtttgggcaa ggaccacaga ggctggcatg gagaggccct gcctcctcct actcctcctg
     2941 tctccttacc tgaaaaggag gggagggatg gataaaggaa tgggtaaaca aaattaattg
     3001 gtaacacata aagttagtaa atgaataaat acaattaaat aaatgaa
//
