LOCUS       NM_015039               5441 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens nicotinamide nucleotide adenylyltransferase 2
            (NMNAT2), transcript variant 1, mRNA.
ACCESSION   NM_015039
VERSION     NM_015039.4
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 5441)
  AUTHORS   Chen,H., Zhang,X., Liao,N., Ji,Y., Mi,L., Gan,Y., Su,Y. and Wen,F.
  TITLE     Downregulation of SIRT6 and NMNAT2 is associated with proliferative
            diabetic retinopathy
  JOURNAL   Mol Vis 29, 160-168 (2023)
   PUBMED   38222451
  REMARK    GeneRIF: Downregulation of SIRT6 and NMNAT2 is associated with
            proliferative diabetic retinopathy.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5441)
  AUTHORS   Challa,S., Khulpateea,B.R., Nandu,T., Camacho,C.V., Ryu,K.W.,
            Chen,H., Peng,Y., Lea,J.S. and Kraus,W.L.
  TITLE     Ribosome ADP-ribosylation inhibits translation and maintains
            proteostasis in cancers
  JOURNAL   Cell 184 (17), 4531-4546 (2021)
   PUBMED   34314702
REFERENCE   3  (bases 1 to 5441)
  AUTHORS   Lukacs,M., Gilley,J., Zhu,Y., Orsomando,G., Angeletti,C., Liu,J.,
            Yang,X., Park,J., Hopkin,R.J., Coleman,M.P., Zhai,R.G. and
            Stottmann,R.W.
  TITLE     Severe biallelic loss-of-function mutations in nicotinamide
            mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with
            fetal akinesia deformation sequence
  JOURNAL   Exp Neurol 320, 112961 (2019)
   PUBMED   31136762
  REMARK    GeneRIF: we present the first human variants in NMNAT2 identified
            in two fetuses with severe skeletal muscle hypoplasia and fetal
            akinesia. Functional studies in vitro showed that the mutations
            impair both NMNAT2 NAD(+) synthase and chaperone functions. This
            work identifies the critical role of NMNAT2 in human development.
REFERENCE   4  (bases 1 to 5441)
  AUTHORS   Huppke,P., Wegener,E., Gilley,J., Angeletti,C., Kurth,I.,
            Drenth,J.P.H., Stadelmann,C., Barrantes-Freer,A., Bruck,W.,
            Thiele,H., Nurnberg,P., Gartner,J., Orsomando,G. and Coleman,M.P.
  TITLE     Homozygous NMNAT2 mutation in sisters with polyneuropathy and
            erythromelalgia
  JOURNAL   Exp Neurol 320, 112958 (2019)
   PUBMED   31132363
  REMARK    GeneRIF: We identified a homozygous missense mutation in the gene
            encoding NAD synthesizing enzyme NMNAT2 in two siblings with
            childhood onset polyneuropathy with erythromelalgia
REFERENCE   5  (bases 1 to 5441)
  AUTHORS   Gilley,J., Mayer,P.R., Yu,G. and Coleman,M.P.
  TITLE     Low levels of NMNAT2 compromise axon development and survival
  JOURNAL   Hum Mol Genet 28 (3), 448-458 (2019)
   PUBMED   30304512
REFERENCE   6  (bases 1 to 5441)
  AUTHORS   Yalowitz,J.A., Xiao,S., Biju,M.P., Antony,A.C., Cummings,O.W.,
            Deeg,M.A. and Jayaram,H.N.
  TITLE     Characterization of human brain nicotinamide 5'-mononucleotide
            adenylyltransferase-2 and expression in human pancreas
  JOURNAL   Biochem J 377 (Pt 2), 317-326 (2004)
   PUBMED   14516279
  REMARK    GeneRIF: Nicotinamide 5'-mononucleotide adenylyltransferase-2 is
            markedly expressed in the islets of Langerhans.
REFERENCE   7  (bases 1 to 5441)
  AUTHORS   Magni,G., Amici,A., Emanuelli,M., Orsomando,G., Raffaelli,N. and
            Ruggieri,S.
  TITLE     Enzymology of NAD+ homeostasis in man
  JOURNAL   Cell Mol Life Sci 61 (1), 19-34 (2004)
   PUBMED   14704851
  REMARK    Review article
REFERENCE   8  (bases 1 to 5441)
  AUTHORS   Raffaelli,N., Sorci,L., Amici,A., Emanuelli,M., Mazzola,F. and
            Magni,G.
  TITLE     Identification of a novel human nicotinamide mononucleotide
            adenylyltransferase
  JOURNAL   Biochem Biophys Res Commun 297 (4), 835-840 (2002)
   PUBMED   12359228
  REMARK    GeneRIF: cloning, isolation and kinetics
REFERENCE   9  (bases 1 to 5441)
  AUTHORS   Sood,R., Bonner,T.I., Makalowska,I., Stephan,D.A., Robbins,C.M.,
            Connors,T.D., Morgenbesser,S.D., Su,K., Faruque,M.U., Pinkett,H.,
            Graham,C., Baxevanis,A.D., Klinger,K.W., Landes,G.M., Trent,J.M.
            and Carpten,J.D.
  TITLE     Cloning and characterization of 13 novel transcripts and the human
            RGS8 gene from the 1q25 region encompassing the hereditary prostate
            cancer (HPC1) locus
  JOURNAL   Genomics 73 (2), 211-222 (2001)
   PUBMED   11318611
REFERENCE   10 (bases 1 to 5441)
  AUTHORS   Robertson,N.G., Khetarpal,U., Gutierrez-Espeleta,G.A., Bieber,F.R.
            and Morton,C.C.
  TITLE     Isolation of novel and known genes from a human fetal cochlear cDNA
            library using subtractive hybridization and differential screening
  JOURNAL   Genomics 23 (1), 42-50 (1994)
   PUBMED   7829101
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF288395.1, AL354953.16 and
            BI493003.1.
            
            On Nov 22, 2018 this sequence version replaced NM_015039.3.
            
            Summary: This gene product belongs to the nicotinamide
            mononucleotide adenylyltransferase (NMNAT) enzyme family, members
            of which catalyze an essential step in NAD (NADP) biosynthetic
            pathway. Unlike the other human family member, which is localized
            to the nucleus, and is ubiquitously expressed; this enzyme is
            cytoplasmic, and is predominantly expressed in the brain. Two
            transcript variants encoding different isoforms have been found for
            this gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and  encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on 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 :: SRR1803612.66213.1,
                                           SRR1803615.231628.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000287713.7/ ENSP00000287713.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3374              AF288395.1         225-3598
            3375-5407           AL354953.16        154293-156325       c
            5408-5441           BI493003.1         20-53               c
FEATURES             Location/Qualifiers
     source          1..5441
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q25.3"
     gene            1..5441
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="nicotinamide nucleotide adenylyltransferase 2"
                     /db_xref="GeneID:23057"
                     /db_xref="HGNC:HGNC:16789"
                     /db_xref="MIM:608701"
     exon            1..198
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     CDS             114..1037
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /EC_number="2.7.7.1"
                     /EC_number="2.7.7.18"
                     /note="isoform 1 is encoded by transcript variant 1;
                     pyridine nucleotide adenylyltransferase 2; NaMN
                     adenylyltransferase 2; NMN adenylyltransferase 2;
                     nicotinamide mononucleotide adenylyltransferase 2;
                     nicotinate-nucleotide adenylyltransferase 2; NMN/NaMN
                     adenylyltransferase 2; nicotinamide/nicotinic acid
                     mononucleotide adenylyltransferase 2"
                     /codon_start=1
                     /product="nicotinamide/nicotinic acid mononucleotide
                     adenylyltransferase 2 isoform 1"
                     /protein_id="NP_055854.1"
                     /db_xref="CCDS:CCDS1353.1"
                     /db_xref="GeneID:23057"
                     /db_xref="HGNC:HGNC:16789"
                     /db_xref="MIM:608701"
                     /translation="MTETTKTHVILLACGSFNPITKGHIQMFERARDYLHKTGRFIVI
                     GGIVSPVHDSYGKQGLVSSRHRLIMCQLAVQNSDWIRVDPWECYQDTWQTTCSVLEHH
                     RDLMKRVTGCILSNVNTPSMTPVIGQPQNETPQPIYQNSNVATKPTAAKILGKVGESL
                     SRICCVRPPVERFTFVDENANLGTVMRYEEIELRILLLCGSDLLESFCIPGLWNEADM
                     EVIVGDFGIVVVPRDAADTDRIMNHSSILRKYKNNIMVVKDDINHPMSVVSSTKSRLA
                     LQHGDGHVVDYLSQPVIDYILKSQLYINASG"
     exon            199..287
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            288..355
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            356..434
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            435..561
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            562..642
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            643..687
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            688..764
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            765..866
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            867..934
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     exon            935..5441
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5303..5308
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="hexamer: AATAAA"
     polyA_site      5328
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="major polyA site"
     regulatory      5418..5423
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="hexamer: AATAAA"
     regulatory      5422..5427
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="hexamer: AATAAG"
     polyA_site      5436
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
     polyA_site      5441
                     /gene="NMNAT2"
                     /gene_synonym="C1orf15; PNAT2"
                     /note="major polyA site"
ORIGIN      
        1 ggagtccaca gcatccaccg ccggagcctc gccttccttt ctccctctgc agacacaacg
       61 agacacaaaa agagaggcaa cccctagacc accgcgaagg acccatctgc accatgaccg
      121 agaccaccaa gacccacgtt atcttgctcg cctgcggcag cttcaatccc atcaccaaag
      181 ggcacattca gatgtttgaa agagccaggg attatctgca caaaactgga aggtttattg
      241 tgattggcgg gattgtctcc cctgtccacg actcctatgg aaaacagggc ctcgtgtcaa
      301 gccggcaccg tctcatcatg tgtcagctgg ccgtccagaa ttctgattgg atcagggtgg
      361 acccttggga gtgctaccag gacacctggc agacgacctg cagcgtgttg gaacaccacc
      421 gggacctcat gaagagggtg actggctgca tcctctccaa tgtcaacaca ccttccatga
      481 cacctgtgat cggacagcca caaaacgaga ccccccagcc catttaccag aacagcaacg
      541 tggccaccaa gcccactgca gccaagatct tggggaaggt gggagaaagc ctcagccgga
      601 tctgctgtgt ccgcccgccg gtggagcgtt tcacctttgt agatgagaat gccaatctgg
      661 gcacggtgat gcggtatgaa gagattgagc tacggatcct gctgctgtgt ggtagtgacc
      721 tgctggagtc cttctgcatc ccagggctct ggaacgaggc agatatggag gtgattgttg
      781 gtgactttgg gattgtggtg gtgccccggg atgcagccga cacagaccga atcatgaatc
      841 actcctcaat actccgcaaa tacaaaaaca acatcatggt ggtgaaggat gacatcaacc
      901 atcccatgtc tgttgtcagc tcaaccaaga gcaggctggc cctgcagcat ggggacggcc
      961 atgttgtgga ttacctgtcc cagccggtca tcgactacat cctcaaaagc cagctgtaca
     1021 tcaatgcctc cggctagcag cccctcgtcc tccggcaaca caatggcccc tccatctttg
     1081 tcagccccct gtttctctcc tgcctctctg tttctccatc tcctcgtctt gactgttttc
     1141 cctacttgct gacttaaccc cccatagtgt gggggacctg cagagaacca tggcattccc
     1201 tattccacag tcatctttgg acagactttc ctctagtctc cgggttgggg gtgggtgagg
     1261 gaatggggtg ggagtcgggg gaagtgcagt ccttggagat gtactggtgt ccgtctccca
     1321 gcatgctcta gagaggcggc tctggtgccc atcctcccag cacgctctgg ggaggcggct
     1381 ctggtgccca tcctcccagc atgctctaga gaggcggctc tggtgcccct cctcccagca
     1441 tgctctgggg aggcggctct ggctcttgcc ttcccagcat gccctttact acaaagggct
     1501 atttttcttt tctttctttt gtttatttat ttttctttgt tcactccctg tagaacttgg
     1561 atgaaatcag tgtccatggt tctttatgtt tgtagtcttg atgtgctcct gtggtattac
     1621 ttcccctctg ataggacatt gtagccagcc tcagcactca gtgagttcat cagggccaca
     1681 cccagtagag aaggccaagc aacctccact tcttcagcac cacacacacg cacacacaca
     1741 cacacgcaca catgcgtgtg cacccgcgca cgcacataca cacacacata tagcagtagc
     1801 agcagcagca gcagcagcag caacctttga tcaggagtga gattttcggg ttctgaaacc
     1861 tgggacacga gtctgtgaat agtcggtttt ctcagaataa tttgaatctg ttttcttagt
     1921 ttcaaatgac catttccctg atgctctgag cttatgatca cacagagcca gtccatcctc
     1981 atttcctggt ggcatctgtt catttacctt tgtggactgt agctgatggc acagtgcggg
     2041 ttccctacca gccaggggtt tccaagggac ctttggaggc catgcttaga cacattcctg
     2101 tacctgagaa caaccacata ggcaggacca gatccacatc gtgcagtcgt gtcataaaaa
     2161 aacaaaacaa aacaaaaaaa cactaggagt ccactcaacc ctggaggtct ttgctaattg
     2221 gaattatgta ttgtctgttg ggctgggaaa tgtctctttc atattgtaag tccaggatga
     2281 actaggagaa agcaatttgt tgccctgatg ataactgatg attttcaccc tctctagctg
     2341 aggtaactca gacagtgcat gaggtcagtt tcttcttgag aagcagtgcc ttggtcttgt
     2401 ttctgtggtt ggttctagcc cctgcagagc ctgggagctg caggaactgt ctgagaaaat
     2461 ctccctaata ggggagtggg ttcccagaag ggagatctgg gaggggtcag gagccactaa
     2521 gttgcttcac tccttttttc tctaattttc taccttcctc tctgttcctg cagacagttt
     2581 tgccagcttt gcttctggtt actagggtct catgcgtgtc ctgcttggag agccataagg
     2641 aaattgctgt cttgtgcttt gtgtctctca tccagtctct ggctcttggg attctggtct
     2701 ttgagaaata gtccctgagt attaggatac ttttatcaaa atctagtacc agctacggcc
     2761 agaaagggcc aggtgggacc tgaaagcaaa gacaatgttc tttaccacac gtttcacatc
     2821 tgcaacatcc ttcaattgcg ggaaaaggaa cttgatttaa cagaagaaca tggtagagca
     2881 gcatccagaa agtctgttat tcctcttgga ttttttgaaa taatcttcag aggaaggaag
     2941 gaaaatccta ttttggggta tcagtgtttg actagggatc atgaaataat aaactgaaaa
     3001 aaactttaga gttcagttga tccaacactt tcctttaaaa gttgagggag cagaggccca
     3061 tgggattaaa tggctggtcc aggtcagcca gcaggtgtag ggcctgacaa gaacatattg
     3121 tttccctgac ccctaggccg tcacaccaca ccctccattt cctcatgttg ctgaccaggt
     3181 gcccatatga tttctacact tcccaagcct taccctggca tctttctttt aaattatatc
     3241 tgtcccaggt gctctccaca cataggatgg taatgccagt cccaggggag ggtgtgatag
     3301 taaggaaggc cactgttagg tttcctttag aaataaagag atctcagcag cttggaagaa
     3361 atcccagaag cggactccat caatccaaga aagagttgct ttgtggaagg tgaaggaaga
     3421 cccacagagt gctcaggatg atgctattgc tggagagcga aagatggaac agccttgtcc
     3481 aggcagaaca gtcataagcc aggaaatgaa acaaaggaaa acaggtgcct gaatttcctg
     3541 gggaaacatg gcttgtttaa ggacttggag ttatggatgg aatttatggg acccacgtga
     3601 gcagacctga ggaaggctcg atttcttttg tttcttggtc cactctgtca ctctgctctg
     3661 gtcaagcccc atttggtcta cagcccatga gaaggaatga ggctggttct gcactctcag
     3721 catgcagtcc gaaagcatgt gggagtgggg agggaaagtg agatgaatta agacaaagaa
     3781 caggtgccat agaagtagat ttctaggaat gaagtggggc agatcttatc tttgtggatt
     3841 acaggcactg tactaaaaac aggtttccta tttaatataa aaagaaagtg aatcttcttt
     3901 tggatagaat catccattcc catcgccgca ccccctaccc cccaaacaca cacacacaca
     3961 cacacacaca cacacacaca cacacacaca cacacgccct actcttcatt tgctagggga
     4021 aggtcacagc acaactaaat ccaggacagg acattgtgac catgacccag ccacagtcaa
     4081 taccagaaag atgattcaga gtctgaagtg gtgccccagg tgccaacagg ataacctcta
     4141 ccccccgact ttgtctctgg ggtcctgttc cttcctgcaa agcccaatcc aagactggca
     4201 tggctcagag gttgtgagaa aggcatggac tggaacaatc atgtccagag gggtctggag
     4261 ctttgtttcc tgttcaccag caaaaaatgt ctctcccatt tttctgaaag tggctgatgt
     4321 aagaacaggc agaaggaaaa ccctttttgt caataactct gtccttaagg aatggtcctc
     4381 tgggagggct gtgctgctag tgggtacctc agtcacacac ccccaacccc aggcagcctc
     4441 tagagccttc ttgctttcat tttccttgaa tgtacatagg aacaaggggg aaagtctctt
     4501 actgaagtgc ctgaaaccca aagctagagc ttctagagac gccgttcttc ctgtctcagc
     4561 ttggccagcc tttcaacaat gttctctagt ttcaagctcc agcttctcag aaagaattaa
     4621 agaacttgct gttcaaatta agtagaaagt gagactcaat aataactgaa ctacagcaaa
     4681 aggcagagaa ttacagggag aaaaaacttg tacttaccag cccaattcta ctctcctcaa
     4741 actgacacac acacacacac acacacacac acacacacac acacactctt ttaggggact
     4801 aagagagaga agcatgttat tacattttac tcatccaaac agtaatgcaa aaataaaacg
     4861 gtagaatatg aaaagctcag gatctctccc aaggctacct actgcaggag ggccaacagg
     4921 tgagatggga agaatggaaa cagggaccga ttttgtagct catacaatta ggacacctta
     4981 ggaatagcat tgtagtaatg gtgatgaata tgctctgcca aattcatcca gtctgcacca
     5041 tcttatagct gcccagcaca ctcgactgtt catgtggtct ctttgtagtg tgagtttgga
     5101 gtgtcctatt agcctgttct ggttaggaat gagttaacgg ctctttccct caaccttagt
     5161 ctagtcccag ggctgaggat tcagctggat ccacatggtc ttgagggttg gcatgaggag
     5221 ggggaagctt ttttgaatcg ctttttgatc acataatctg ccattttaag agtaagattt
     5281 gctttatgga aatcaattca ttaataaaaa atgatattca agttgcaata ccatttcaca
     5341 gtgaaatatt ttgagtacaa ttttgttgct agaatagtca tgggcaagag ttttatgcaa
     5401 aatgtttcaa ttatgttaat aaataagaca atgctacaag a
//
