LOCUS       NM_001085411            4011 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens NAD kinase 2, mitochondrial (NADK2), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001085411
VERSION     NM_001085411.3
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 4011)
  AUTHORS   Kim,H., Fu,Z., Yang,Z., Song,Z., Shamsa,E.H., Yumnamcha,T., Sun,S.,
            Liu,W., Ibrahim,A.S., Qi,N.R., Zhang,R. and Zhang,K.
  TITLE     The mitochondrial NAD kinase functions as a major metabolic
            regulator upon increased energy demand
  JOURNAL   Mol Metab 64, 101562 (2022)
   PUBMED   35944895
  REMARK    GeneRIF: The mitochondrial NAD kinase functions as a major
            metabolic regulator upon increased energy demand.
            GeneRIF: Deleting MNADK (NADK2) in mice reduced fat oxidation upon
            energy demand triggered by endurance exercise or fasting. NADK2 is
            a major metabolic regulator upon increased energy demand.
REFERENCE   2  (bases 1 to 4011)
  AUTHORS   Mary,C., Soflaee,M.H., Kesavan,R., Gelin,M., Brown,H.,
            Zacharias,G., Mathews,T.P., Lemoff,A., Lionne,C., Labesse,G. and
            Hoxhaj,G.
  TITLE     Crystal structure of human NADK2 reveals a dimeric organization and
            active site occlusion by lysine acetylation
  JOURNAL   Mol Cell 82 (17), 3299-3311 (2022)
   PUBMED   35868311
  REMARK    GeneRIF: Crystal structure of human NADK2 reveals a dimeric
            organization and active site occlusion by lysine acetylation.
REFERENCE   3  (bases 1 to 4011)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   4  (bases 1 to 4011)
  AUTHORS   Zhu,J., Schworer,S., Berisa,M., Kyung,Y.J., Ryu,K.W., Yi,J.,
            Jiang,X., Cross,J.R. and Thompson,C.B.
  TITLE     Mitochondrial NADP(H) generation is essential for proline
            biosynthesis
  JOURNAL   Science 372 (6545), 968-972 (2021)
   PUBMED   33888598
  REMARK    GeneRIF: Mitochondrial NADP(H) generation is essential for proline
            biosynthesis.
REFERENCE   5  (bases 1 to 4011)
  AUTHORS   Pomerantz,D.J., Ferdinandusse,S., Cogan,J., Cooper,D.N.,
            Reimschisel,T., Robertson,A., Bican,A., McGregor,T., Gauthier,J.,
            Millington,D.S., Andrae,J.L.W., Tschannen,M.R., Helbling,D.C.,
            Demos,W.M., Denis,S., Wanders,R.J.A., Newman,J.N., Hamid,R. and
            Phillips,J.A. 3rd.
  CONSRTM   Collaborators of UDN
  TITLE     Clinical heterogeneity of mitochondrial NAD kinase deficiency
            caused by a NADK2 start loss variant
  JOURNAL   Am J Med Genet A 176 (3), 692-698 (2018)
   PUBMED   29388319
  REMARK    GeneRIF: Our findings also clarify the mechanism underlying NADK2
            deficiency and suggest that this disease should be ruled out in
            cases of hyperlysinemia, especially those with visual loss, and
            neurological phenotypes.
            Review article
REFERENCE   6  (bases 1 to 4011)
  AUTHORS   Tort,F., Ugarteburu,O., Torres,M.A., Garcia-Villoria,J., Giros,M.,
            Ruiz,A. and Ribes,A.
  TITLE     Lysine Restriction and Pyridoxal Phosphate Administration in a
            NADK2 Patient
  JOURNAL   Pediatrics 138 (5) (2016)
   PUBMED   27940755
  REMARK    GeneRIF: The use of whole exome sequencing has allowed us to
            identify a new homozygous mutation in NADK2, leading to a premature
            stop codon and absence of protein. To our knowledge this is the
            second reported individual with mutations in NADK2.
REFERENCE   7  (bases 1 to 4011)
  AUTHORS   Houten,S.M., Denis,S., Te Brinke,H., Jongejan,A., van Kampen,A.H.,
            Bradley,E.J., Baas,F., Hennekam,R.C., Millington,D.S., Young,S.P.,
            Frazier,D.M., Gucsavas-Calikoglu,M. and Wanders,R.J.
  TITLE     Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes
            dienoyl-CoA reductase deficiency with hyperlysinemia
  JOURNAL   Hum Mol Genet 23 (18), 5009-5016 (2014)
   PUBMED   24847004
  REMARK    GeneRIF: An autosomal recessive defect in NADK2 causes
            mitochondrial NADPH deficiency with secondary deficiencies in
            several mitochondrial processes including polyunsaturated fatty
            acid oxidation and lysine degradation.
REFERENCE   8  (bases 1 to 4011)
  AUTHORS   Zhang,R.
  TITLE     MNADK, a novel liver-enriched mitochondrion-localized NAD kinase
  JOURNAL   Biol Open 2 (4), 432-438 (2013)
   PUBMED   23616928
  REMARK    GeneRIF: MNADK is localized to mitochondria in Hep G2 cells, and a
            recombinant MNADK showed NAD kinase activity. MNADK is abundant in
            mitochondrion-rich tissues, such as liver. MNADK expression was
            suppressed in human liver tumors. Identification of MNADK
            immediately suggests a model in which NADK and MNADK are
            responsible for de novo synthesis of NADP(+) in cytosol and
            mitochondria, respectively.
            Publication Status: Online-Only
REFERENCE   9  (bases 1 to 4011)
  AUTHORS   Ohashi,K., Kawai,S. and Murata,K.
  TITLE     Identification and characterization of a human mitochondrial NAD
            kinase
  JOURNAL   Nat Commun 3, 1248 (2012)
   PUBMED   23212377
  REMARK    GeneRIF: exhibits NAD kinase activity, utilizing ATP or inorganic
            polyphosphate, and is localized in mitochondria of HEK293A cells
REFERENCE   10 (bases 1 to 4011)
  AUTHORS   Adams,M.D., Kerlavage,A.R., Fleischmann,R.D., Fuldner,R.A.,
            Bult,C.J., Lee,N.H., Kirkness,E.F., Weinstock,K.G., Gocayne,J.D.,
            White,O. et al.
  TITLE     Initial assessment of human gene diversity and expression patterns
            based upon 83 million nucleotides of cDNA sequence
  JOURNAL   Nature 377 (6547 Suppl), 3-174 (1995)
   PUBMED   7566098
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC008807.10, AI377881.1,
            BC062567.1, BX648388.1, BM990433.1 and HY336341.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001085411.2.
            
            Summary: This gene encodes a mitochondrial kinase that catalyzes
            the phosphorylation of NAD to yield NADP. Mutations in this gene
            result in 2,4-dienoyl-CoA reductase deficiency. Alternative
            splicing results in multiple transcript variants. [provided by
            RefSeq, Oct 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longer isoform (1).
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660803.33485.1,
                                           SRR1803613.280195.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2162895, SAMEA2467148
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000381937.9/
                                                  ENSP00000371362.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-151               AC008807.10        47121-47271
            152-633             AI377881.1         1-482
            634-2887            BC062567.1         254-2507
            2888-3126           BX648388.1         2490-2728
            3127-3715           BX648388.1         2730-3318
            3716-4008           BM990433.1         18-310              c
            4009-4011           HY336341.1         29-31               c
FEATURES             Location/Qualifiers
     source          1..4011
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5p13.2"
     gene            1..4011
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /note="NAD kinase 2, mitochondrial"
                     /db_xref="GeneID:133686"
                     /db_xref="HGNC:HGNC:26404"
                     /db_xref="MIM:615787"
     exon            1..427
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     CDS             128..1456
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /EC_number="2.7.1.23"
                     /note="isoform 1 is encoded by transcript variant 1; NAD
                     kinase domain-containing protein 1, mitochondrial"
                     /codon_start=1
                     /product="NAD kinase 2, mitochondrial isoform 1"
                     /protein_id="NP_001078880.1"
                     /db_xref="CCDS:CCDS47197.1"
                     /db_xref="GeneID:133686"
                     /db_xref="HGNC:HGNC:26404"
                     /db_xref="MIM:615787"
                     /translation="MTCYRGFLLGSCCRVAGGRAAALRGPGAGGPAARPRLGGDGGGR
                     RHLGQGQPRELAGCGSRADGGFRPSRVVVVAKTTRYEFEQQRYRYAELSEEDLKQLLA
                     LKGSSYSGLLERHHIHTKNVEHIIDSLRNEGIEVRLVKRREYDEETVRWADAVIAAGG
                     DGTMLLAASKVLDRLKPVIGVNTDPERSEGHLCLPVRYTHSFPEALQKFYRGEFRWLW
                     RQRIRLYLEGTGINPVPVDLHEQQLSLNQHNRALNIERAHDERSEASGPQLLPVRALN
                     EVFIGESLSSRASYYEISVDDGPWEKQKSSGLNLCTGTGSKAWSFNINRVATQAVEDV
                     LNIAKRQGNLSLPLNRELVEKVTNEYNESLLYSPEEPKILFSIREPIANRVFSSSRQR
                     CFSSKVCVRSRCWDACMVVDGGTSFEFNDGAIASMMINKEDELRTVLLEQ"
     exon            428..516
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            517..605
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            606..687
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            688..771
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            772..908
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            909..987
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            988..1083
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            1084..1139
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            1140..1193
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            1194..1317
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..4011
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3695..3700
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /note="hexamer: AATAAA"
     polyA_site      3715
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /note="major polyA site"
     regulatory      3881..3886
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /note="hexamer: ATTAAA"
     polyA_site      3903
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
     regulatory      3986..3991
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
                     /note="hexamer: ATTAAA"
     polyA_site      4011
                     /gene="NADK2"
                     /gene_synonym="C5orf33; DECRD; MNADK; NADKD1"
ORIGIN      
        1 gcacttaacc tctgcccgtc cggcgcgaag ttagaggccc gggcggcgcg gacggcgcgc
       61 actcccggcg gtagggagct gaggcaaggg gcccgagccc aagcccgcgg ccgcggcccg
      121 gcccacgatg acttgctacc gaggcttctt gctgggcagc tgttgtcgcg tggcgggcgg
      181 ccgggcggcg gcgctgcggg gaccgggtgc gggaggcccc gccgcgcggc cccggctggg
      241 cggtgacggt ggcggccggc ggcacctggg gcaggggcag ccgcgcgagc tggcgggctg
      301 tggcagccgc gcggacggcg gcttccgccc ctcccgggtg gtggtggtgg ccaaaaccac
      361 ccggtacgag ttcgagcagc agcggtaccg ttacgcggag ctctcggagg aggacctgaa
      421 gcagctgctt gcattgaaag gctctagtta cagtggactt cttgaacgac atcatattca
      481 caccaaaaat gtagaacata ttatagatag tttacggaat gagggaattg aggttcgtct
      541 agtaaagagg agagaatatg atgaagagac tgttcgatgg gcagatgctg tcatagctgc
      601 aggaggtgat ggcacaatgc tgctggcagc gagtaaagtc ttggacagac ttaaaccagt
      661 tataggggta aacactgatc cagaacggtc tgagggtcat ttatgcctgc ccgttcgata
      721 tacacattcc tttccagaag ccttacagaa gttctatcgt ggtgagttca ggtggttgtg
      781 gaggcagaga atcaggttat accttgaagg gactggcata aaccctgtac ctgtggacct
      841 tcacgagcag cagctaagct tgaatcagca caatagagcc cttaacattg aaagagctca
      901 tgatgaaagg tctgaggctt caggacccca acttctgcca gtgagagcac taaatgaagt
      961 cttcattggg gagagtctgt catccagggc ttcctactat gagatttcag ttgatgatgg
     1021 tccatgggaa aaacagaaga gttcagggct caatttgtgt actggaacag gatcaaaggc
     1081 ctggtcattc aatattaaca gggttgcaac tcaggctgta gaagatgttt taaatattgc
     1141 aaaacgacaa ggaaatttga gtcttccatt gaacagagaa ttggtagaga aagtaacaaa
     1201 tgaatataat gaatcactgc tctacagtcc ggaagaacca aaaatacttt tcagtattcg
     1261 agaaccaata gcaaatagag ttttctcaag cagtcgtcag cgttgtttct cctcaaaggt
     1321 ttgtgttcgt tctcgttgtt gggatgcctg tatggttgtg gatggaggaa cttcttttga
     1381 gtttaatgat ggtgcaattg cttcgatgat gatcaataaa gaagatgagc ttcgaactgt
     1441 gcttcttgaa cagtgaagga tttcctcatg acaaattttg attactggcg agaatatttt
     1501 tacttcagaa acagactacc agtcgtaaag tgacattttt tggttattgt tgagactgct
     1561 tgcccgtggg ctcagaagtg agatttgcat tattcttctg ttggattctg atagaaaaaa
     1621 agacattcac tgtataagaa aatggatgga ctgaaccaat tagaattgat accagtgaaa
     1681 tttttatatt gcttacaatt ggtaaccaag agtgctgata cctttttaaa tttagagggg
     1741 caggcttaaa taaaggacta aatatttagg atttgaaact taactgtata agtgtgtttt
     1801 ccttcccttt cctcctaatt gtgggattgt cagaactgaa cacatatcat ttgattagtg
     1861 catatttttt atagtacctg aaaaccaaga ttttgaaaaa attttcaaga cagagaattt
     1921 tgataaatcc tgacattgac ctaattgaca taggtaaata tgtttgtata tgtgctaata
     1981 attttctaat ttcggaacac gatgatgtta tgactattga tttaaaaatt tcaaataata
     2041 atttttgaaa ttatagatga atgctttcat ttgagtttca ttctgtaatt cagcagttct
     2101 gggtgaaata cagatagcaa aacaaatcat gatgctgtta caaatgtatt agttatccaa
     2161 taagtgtttt aagtcaattt ttttaaaatg atatgagtct tacaggtttc ttccatcttt
     2221 aaaatgctca aacatggatt cagggactaa aaggatgaac tgattagaca ttttctatta
     2281 ggagtttggt aaaatattgt aaaaatatct tcacctgtgt taggagtatt atcagaaaga
     2341 atggattctt taataaatat gtaaaacaca gtagttttgg aattgccttc cttagtattg
     2401 tggttttcac ctagcttata ttccaagatt tacagaatag cttttaggat aagatgttag
     2461 gacttttttt ttttccccat gagaattcct ttatttttgg aggaaattat tatctaatta
     2521 ttgatctact tataagtaat cctagaattt ttgccaaaag atcctgtcgt tgcataatca
     2581 aacagttggt attctcgtgc cgttgttcaa agtcatgtgt ttctttcatt tggtgctgaa
     2641 aatttctgtt caatcattga caaatattta ttgaacaccc actctgtgcc atgtaaaact
     2701 atgtcaggtg ctggatatgt tgatgaatga aacagactct atccttatac aatttgagtc
     2761 ttgtgggctc agaagtaaat tctgtgaaag ctggacggat agtcgaattg agtgctctta
     2821 gttttgccaa tatttaacat gttgttctta tcaatttttt aaaataaatg ttaatgtaca
     2881 aagttaatct aggttttgat gtatatccag agaatcaatt tttcttaaag tatctgcgta
     2941 gacattcata gcaaagaatt tatgacatat cagatagaaa tacattaaaa tgtagtgttt
     3001 tcccagagat tgatctggct tttttttttt gatatacata agataccact ttataaagaa
     3061 gctccatact atagaacctc ccctaacagg cttaaaatac cttctttttt tttttttttt
     3121 tttttgagaa cggagtcttg ctttgtcacc caggctggac tgcagtggca tgatctcggc
     3181 tctgcaacct ccatctccca ggttcaagcg attctcctgc ctcagcctcc caagtagctg
     3241 ggattacagg caggcaccac tatgcctggc taattttttg tatttttagt agatatgggg
     3301 attcaccatg ttggtcaggc tggtctcgaa ctcctgacct tgtgatctgc ctgcctcggc
     3361 ctcccagtat tgggattaca ggcatgagcc accatgcccg gccttaaaat gccttcttaa
     3421 aggaaaaatg ccaactccat ccttaatctc aaggaaatct gattgtccaa atagatctgt
     3481 taatatgtaa catattaata ggtaacttgc tgtgtaaaat tataagccat attttaaaag
     3541 gttttaaaaa tacttattgt gctccatttg tgatataatt tctaacattt ctgctctgtg
     3601 atgggggttt atttgtaaga ataagaggca aaggaatgtt agcatagcaa aaatgtgttt
     3661 gaatgagtta accttttaat cgcaacccta tgtgaataaa attactccac tgttacctct
     3721 tctttttaac atttcttatt tccctctcaa ggggtcatta tttgaaaact agttttcaca
     3781 aaatgttatg tttcagaagt gtttccccac tgctgtgtat tattattctg tgccctgttg
     3841 acttcattca ctgttaacat ttgacataga atgattagtt attaaatcag ggtgaagtgc
     3901 ttacctggtc agtgtaggct cttcagataa ttttgactta atatttttga tactccttgt
     3961 gcatttacat tcatggcccc tgtacattaa atcatattac atgttttact a
//
