LOCUS       NM_007254               1731 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens polynucleotide kinase 3'-phosphatase (PNKP), mRNA.
ACCESSION   NM_007254
VERSION     NM_007254.4
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 1731)
  AUTHORS   Chakraborty,A., Sreenivasmurthy,S.G., Miller,W., Huai,W.,
            Biswas,T., Mandal,S.M., Bosca,L., Krishnan,B., Ghosh,G. and
            Hazra,T.
  TITLE     Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and
            ameliorates neurodegenerative symptoms in Huntington's disease
  JOURNAL   Proc Natl Acad Sci U S A 121 (39), e2406308121 (2024)
   PUBMED   39298485
  REMARK    GeneRIF: Fructose-2,6-bisphosphate restores DNA repair activity of
            PNKP and ameliorates neurodegenerative symptoms in Huntington's
            disease.
REFERENCE   2  (bases 1 to 1731)
  AUTHORS   Islam,A., Chakraborty,A., Sarker,A.H., Aryal,U.K., Pan,L.,
            Sharma,G., Boldogh,I. and Hazra,T.
  TITLE     Site-specific acetylation of polynucleotide kinase 3'-phosphatase
            regulates its distinct role in DNA repair pathways
  JOURNAL   Nucleic Acids Res 52 (5), 2416-2433 (2024)
   PUBMED   38224455
  REMARK    GeneRIF: Site-specific acetylation of polynucleotide kinase
            3'-phosphatase regulates its distinct role in DNA repair pathways.
REFERENCE   3  (bases 1 to 1731)
  AUTHORS   Lee,C.Y., Hubrich,D., Varga,J.K., Schafer,C., Welzel,M.,
            Schumbera,E., Djokic,M., Strom,J.M., Schonfeld,J., Geist,J.L.,
            Polat,F., Gibson,T.J., Keller Valsecchi,C.I., Kumar,M.,
            Schueler-Furman,O. and Luck,K.
  TITLE     Systematic discovery of protein interaction interfaces using
            AlphaFold and experimental validation
  JOURNAL   Mol Syst Biol 20 (2), 75-97 (2024)
   PUBMED   38225382
REFERENCE   4  (bases 1 to 1731)
  AUTHORS   Shen,J., Gilmore,E.C., Marshall,C.A., Haddadin,M., Reynolds,J.J.,
            Eyaid,W., Bodell,A., Barry,B., Gleason,D., Allen,K., Ganesh,V.S.,
            Chang,B.S., Grix,A., Hill,R.S., Topcu,M., Caldecott,K.W.,
            Barkovich,A.J. and Walsh,C.A.
  TITLE     Mutations in PNKP cause microcephaly, seizures and defects in DNA
            repair
  JOURNAL   Nat Genet 42 (3), 245-249 (2010)
   PUBMED   20118933
  REMARK    GeneRIF: The neurological abnormalities in individuals with
            microcephaly, early onset, intractable seizures and develomental
            delays may reflect a role for PNKP in several DNA repair pathways.
REFERENCE   5  (bases 1 to 1731)
  AUTHORS   Chappell,C., Hanakahi,L.A., Karimi-Busheri,F., Weinfeld,M. and
            West,S.C.
  TITLE     Involvement of human polynucleotide kinase in double-strand break
            repair by non-homologous end joining
  JOURNAL   EMBO J 21 (11), 2827-2832 (2002)
   PUBMED   12032095
  REMARK    GeneRIF: Involvement of human polynucleotide kinase in
            double-strand break repair by non-homologous end joining
REFERENCE   6  (bases 1 to 1731)
  AUTHORS   Whitehouse,C.J., Taylor,R.M., Thistlethwaite,A., Zhang,H.,
            Karimi-Busheri,F., Lasko,D.D., Weinfeld,M. and Caldecott,K.W.
  TITLE     XRCC1 stimulates human polynucleotide kinase activity at damaged
            DNA termini and accelerates DNA single-strand break repair
  JOURNAL   Cell 104 (1), 107-117 (2001)
   PUBMED   11163244
REFERENCE   7  (bases 1 to 1731)
  AUTHORS   Karimi-Busheri,F., Daly,G., Robins,P., Canas,B., Pappin,D.J.,
            Sgouros,J., Miller,G.G., Fakhrai,H., Davis,E.M., Le Beau,M.M. and
            Weinfeld,M.
  TITLE     Molecular characterization of a human DNA kinase
  JOURNAL   J Biol Chem 274 (34), 24187-24194 (1999)
   PUBMED   10446193
REFERENCE   8  (bases 1 to 1731)
  AUTHORS   Jilani,A., Ramotar,D., Slack,C., Ong,C., Yang,X.M., Scherer,S.W.
            and Lasko,D.D.
  TITLE     Molecular cloning of the human gene, PNKP, encoding a
            polynucleotide kinase 3'-phosphatase and evidence for its role in
            repair of DNA strand breaks caused by oxidative damage
  JOURNAL   J Biol Chem 274 (34), 24176-24186 (1999)
   PUBMED   10446192
REFERENCE   9  (bases 1 to 1731)
  AUTHORS   Bird,T.D.
  TITLE     Charcot-Marie-Tooth Hereditary Neuropathy Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301532
REFERENCE   10 (bases 1 to 1731)
  AUTHORS   Perlman,S.
  TITLE     Hereditary Ataxia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301317
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC118341.2, BU541073.1 and
            BC033822.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_007254.3.
            
            Summary: This locus represents a gene involved in DNA repair. In
            response to ionizing radiation or oxidative damage, the protein
            encoded by this locus catalyzes 5' phosphorylation and 3'
            dephosphorylation of nucleic acids. Mutations at this locus have
            been associated with microcephaly, seizures, and developmental
            delay.[provided by RefSeq, Sep 2010].
            
            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 :: SRR3476690.200165.1,
                                           SRR3476690.320790.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000322344.8/ ENSP00000323511.2
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                AC118341.2         3259-3269           c
            12-15               BU541073.1         1-4
            16-1731             BC033822.1         1-1716
FEATURES             Location/Qualifiers
     source          1..1731
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.33"
     gene            1..1731
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /note="polynucleotide kinase 3'-phosphatase"
                     /db_xref="GeneID:11284"
                     /db_xref="HGNC:HGNC:9154"
                     /db_xref="MIM:605610"
     exon            1..108
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            109..272
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     CDS             122..1687
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /EC_number="2.7.1.78"
                     /EC_number="3.1.3.32"
                     /note="Homo sapiens polynucleotide kinase 3'-phosphatase
                     (PNKP); DNA 5'-kinase/3'-phosphatase"
                     /codon_start=1
                     /product="bifunctional polynucleotide phosphatase/kinase"
                     /protein_id="NP_009185.2"
                     /db_xref="CCDS:CCDS12783.1"
                     /db_xref="GeneID:11284"
                     /db_xref="HGNC:HGNC:9154"
                     /db_xref="MIM:605610"
                     /translation="MGEVEAPGRLWLESPPGGAPPIFLPSDGQALVLGRGPLTQVTDR
                     KCSRTQVELVADPETRTVAVKQLGVNPSTTGTQELKPGLEGSLGVGDTLYLVNGLHPL
                     TLRWEETRTPESQPDTPPGTPLVSQDEKRDAELPKKRMRKSNPGWENLEKLLVFTAAG
                     VKPQGKVAGFDLDGTLITTRSGKVFPTGPSDWRILYPEIPRKLRELEAEGYKLVIFTN
                     QMSIGRGKLPAEEFKAKVEAVVEKLGVPFQVLVATHAGLYRKPVTGMWDHLQEQANDG
                     TPISIGDSIFVGDAAGRPANWAPGRKKKDFSCADRLFALNLGLPFATPEEFFLKWPAA
                     GFELPAFDPRTVSRSGPLCLPESRALLSASPEVVVAVGFPGAGKSTFLKKHLVSAGYV
                     HVNRDTLGSWQRCVTTCETALKQGKRVAIDNTNPDAASRARYVQCARAAGVPCRCFLF
                     TATLEQARHNNRFREMTDSSHIPVSDMVMYGYRKQFEAPTLAEGFSAILEIPFRLWVE
                     PRLGRLYCQFSEG"
     exon            273..319
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            320..619
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            620..699
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            700..757
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            758..865
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            866..937
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            938..986
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            987..1057
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1058..1150
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1151..1247
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1248..1309
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1310..1419
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1420..1507
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1508..1569
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1570..1731
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1710..1715
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /note="hexamer: AATAAA"
     polyA_site      1731
                     /gene="PNKP"
                     /gene_synonym="AOA4; CMT2B2; EIEE10; MCSZ; PNK"
                     /note="major polyA site"
ORIGIN      
        1 atttccgtcc gccgaggaac cgaccgccgc cggccgggtt gcaggcgggg cacctcgggc
       61 aggacctccc tggtcggaag tggccgtgag cccaagccgc ggtcccgggc cggcacccag
      121 gatgggcgag gtggaggccc cgggccgctt gtggctcgag agcccccctg ggggagcgcc
      181 ccccatcttc ctgccctcgg acgggcaagc cctggtcctg ggcaggggac ccctgaccca
      241 ggttacggac cggaagtgct ccagaactca agtggagctg gtcgcagatc ctgagacccg
      301 gacagtggca gtgaaacagc tgggagttaa cccctcaact accgggaccc aggagttgaa
      361 gccggggttg gagggctctc tgggggtggg ggacacactg tatttggtca atggcctcca
      421 cccactgacc ctgcgctggg aagagacccg cacaccagaa tcccagccag atactccgcc
      481 tggcacccct ctggtgtccc aagatgagaa gagagatgct gagctgccga agaagcgtat
      541 gcggaagtca aaccccggct gggagaactt ggagaagttg ctagtgttca ccgcagctgg
      601 ggtgaaaccc cagggcaagg tggctggctt tgatctggac gggacgctca tcaccacacg
      661 ctctgggaag gtctttccca ctggccccag tgactggagg atcttgtacc cagagattcc
      721 ccgtaagctc cgagagctgg aagccgaggg ctacaagctg gtgatcttca ccaaccagat
      781 gagcatcggg cgcgggaagc tgccagccga ggagttcaag gccaaggtgg aggctgtggt
      841 ggagaagctg ggggtcccct tccaggtgct ggtggccacg cacgcaggct tgtaccggaa
      901 gccggtgacg ggcatgtggg accatctgca ggagcaggcc aacgacggca cgcccatatc
      961 catcggggac agcatctttg tgggagacgc agccggacgc ccggccaact gggccccggg
     1021 gcggaagaag aaagacttct cctgcgccga tcgcctgttt gccctcaacc ttggcctgcc
     1081 cttcgccacg cctgaggagt tctttctcaa gtggccagca gccggcttcg agctcccagc
     1141 ctttgatccg aggactgtct cccgctcagg gcctctctgc ctccccgagt ccagggccct
     1201 cctgagcgcc agcccggagg tggttgtcgc agtgggattc cctggggccg ggaagtccac
     1261 ctttctcaag aagcacctcg tgtcggccgg atatgtccac gtgaacaggg acacgctagg
     1321 ctcctggcag cgctgtgtga ccacgtgtga gacagccctg aagcaaggga aacgggtcgc
     1381 catcgacaac acaaacccag acgccgcgag ccgcgccagg tacgtccagt gtgcccgagc
     1441 cgcgggcgtc ccctgccgct gcttcctctt caccgccact ctggagcagg cgcgccacaa
     1501 caaccggttt cgagagatga cggactcctc tcatatcccc gtgtcagaca tggtcatgta
     1561 tggctacagg aagcagttcg aggccccaac gctggctgaa ggcttctctg ccatcctgga
     1621 gatcccgttc cggctatggg tggagccgag gctggggcgg ctgtactgcc agttctccga
     1681 gggctgagcc ccgcccagct cccctccaca ataaacgctg tttctccttg a
//
