LOCUS       NM_003905               1813 bp    mRNA    linear   PRI 25-JAN-2025
DEFINITION  Homo sapiens NEDD8 activating enzyme E1 subunit 1 (NAE1),
            transcript variant 1, mRNA.
ACCESSION   NM_003905
VERSION     NM_003905.4
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 1813)
  AUTHORS   Muffels,I.J.J., Schene,I.F., Rehmann,H., Massink,M.P.G., van der
            Wal,M.M., Bauder,C., Labeur,M., Armando,N.G., Lequin,M.H.,
            Houben,M.L., Giltay,J.C., Haitjema,S., Huisman,A., Vansenne,F.,
            Bluvstein,J., Pappas,J., Shailee,L.V., Zarate,Y.A., Mokry,M., van
            Haaften,G.W., Nieuwenhuis,E.E.S., Refojo,D., van Wijk,F.,
            Fuchs,S.A. and van Hasselt,P.M.
  TITLE     Bi-allelic variants in NAE1 cause intellectual disability,
            ischiopubic hypoplasia, stress-mediated lymphopenia and
            neurodegeneration
  JOURNAL   Am J Hum Genet 110 (1), 146-160 (2023)
   PUBMED   36608681
REFERENCE   2  (bases 1 to 1813)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   3  (bases 1 to 1813)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   4  (bases 1 to 1813)
  AUTHORS   Jin,Y., Zhang,P., Wang,Y., Jin,B., Zhou,J., Zhang,J. and Pan,J.
  TITLE     Neddylation Blockade Diminishes Hepatic Metastasis by Dampening
            Cancer Stem-Like Cells and Angiogenesis in Uveal Melanoma
  JOURNAL   Clin Cancer Res 24 (15), 3741-3754 (2018)
   PUBMED   29233905
  REMARK    GeneRIF: NAE1 expression was readily detectable in Uveal Melanoma.
            Inhibition of the neddylation pathway by MLN4924 repressed the
            cancer stem-like cells properties in Uveal Melanoma
REFERENCE   5  (bases 1 to 1813)
  AUTHORS   Li,H., Zhou,W., Li,L., Wu,J., Liu,X., Zhao,L., Jia,L. and Sun,Y.
  TITLE     Inhibition of Neddylation Modification Sensitizes Pancreatic Cancer
            Cells to Gemcitabine
  JOURNAL   Neoplasia 19 (6), 509-518 (2017)
   PUBMED   28535453
  REMARK    GeneRIF: Here we report that high expression of neddylation
            components, NEDD8 and NAE1, are associated with poor survival of
            Pancreatic ductal adenocarcinoma patients. Blockage of neddylation
            by MLN4924 significantly sensitizes pancreatic cancer cells to
            gemcitabine, reduced clonogenic survival, decreased invasion
            capacity, increased apoptosis and senescence
REFERENCE   6  (bases 1 to 1813)
  AUTHORS   Chen,Y., McPhie,D.L., Hirschberg,J. and Neve,R.L.
  TITLE     The amyloid precursor protein-binding protein APP-BP1 drives the
            cell cycle through the S-M checkpoint and causes apoptosis in
            neurons
  JOURNAL   J Biol Chem 275 (12), 8929-8935 (2000)
   PUBMED   10722740
REFERENCE   7  (bases 1 to 1813)
  AUTHORS   Hori,T., Osaka,F., Chiba,T., Miyamoto,C., Okabayashi,K.,
            Shimbara,N., Kato,S. and Tanaka,K.
  TITLE     Covalent modification of all members of human cullin family
            proteins by NEDD8
  JOURNAL   Oncogene 18 (48), 6829-6834 (1999)
   PUBMED   10597293
REFERENCE   8  (bases 1 to 1813)
  AUTHORS   Loftus,B.J., Kim,U.J., Sneddon,V.P., Kalush,F., Brandon,R.,
            Fuhrmann,J., Mason,T., Crosby,M.L., Barnstead,M., Cronin,L.,
            Deslattes Mays,A., Cao,Y., Xu,R.X., Kang,H.L., Mitchell,S.,
            Eichler,E.E., Harris,P.C., Venter,J.C. and Adams,M.D.
  TITLE     Genome duplications and other features in 12 Mb of DNA sequence
            from human chromosome 16p and 16q
  JOURNAL   Genomics 60 (3), 295-308 (1999)
   PUBMED   10493829
REFERENCE   9  (bases 1 to 1813)
  AUTHORS   Gong,L. and Yeh,E.T.
  TITLE     Identification of the activating and conjugating enzymes of the
            NEDD8 conjugation pathway
  JOURNAL   J Biol Chem 274 (17), 12036-12042 (1999)
   PUBMED   10207026
REFERENCE   10 (bases 1 to 1813)
  AUTHORS   Chow,N., Korenberg,J.R., Chen,X.N. and Neve,R.L.
  TITLE     APP-BP1, a novel protein that binds to the carboxyl-terminal region
            of the amyloid precursor protein
  JOURNAL   J Biol Chem 271 (19), 11339-11346 (1996)
   PUBMED   8626687
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BM785899.1 and BC000480.2.
            
            On Nov 22, 2018 this sequence version replaced NM_003905.3.
            
            Summary: The protein encoded by this gene binds to the beta-amyloid
            precursor protein. Beta-amyloid precursor protein is a cell surface
            protein with signal-transducing properties, and it is thought to
            play a role in the pathogenesis of Alzheimer's disease. In
            addition, the encoded protein can form a heterodimer with UBE1C and
            bind and activate NEDD8, a ubiquitin-like protein. This protein is
            required for cell cycle progression through the S/M checkpoint.
            Three transcript variants encoding different isoforms have been
            found for this gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the predominant
            isoform (a).
            
            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 :: SRR3476690.483875.1,
                                           SRR3476690.780082.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000290810.8/ ENSP00000290810.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-396               BM785899.1         1-396
            397-1813            BC000480.2         328-1744
FEATURES             Location/Qualifiers
     source          1..1813
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.1"
     gene            1..1813
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /note="NEDD8 activating enzyme E1 subunit 1"
                     /db_xref="GeneID:8883"
                     /db_xref="HGNC:HGNC:621"
                     /db_xref="MIM:603385"
     exon            1..130
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     CDS             78..1682
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /note="isoform a is encoded by transcript variant 1;
                     amyloid beta precursor protein-binding protein 1, 59kD;
                     amyloid beta precursor protein binding protein 1, 59kDa;
                     NEDD8-activating enzyme E1 subunit; amyloid
                     protein-binding protein 1; NEDD8-activating enzyme E1
                     regulatory subunit; protooncogene protein 1; APP-BP1;
                     proto-oncogene protein 1; amyloid beta precursor
                     protein-binding protein 1, 59 kDa"
                     /codon_start=1
                     /product="NEDD8-activating enzyme E1 regulatory subunit
                     isoform a"
                     /protein_id="NP_003896.1"
                     /db_xref="CCDS:CCDS10820.1"
                     /db_xref="GeneID:8883"
                     /db_xref="HGNC:HGNC:621"
                     /db_xref="MIM:603385"
                     /translation="MAQLGKLLKEQKYDRQLRLWGDHGQEALESAHVCLINATATGTE
                     ILKNLVLPGIGSFTIIDGNQVSGEDAGNNFFLQRSSIGKNRAEAAMEFLQELNSDVSG
                     SFVEESPENLLDNDPSFFCRFTVVVATQLPESTSLRLADVLWNSQIPLLICRTYGLVG
                     YMRIIIKEHPVIESHPDNALEDLRLDKPFPELREHFQSYDLDHMEKKDHSHTPWIVII
                     AKYLAQWYSETNGRIPKTYKEKEDFRDLIRQGILKNENGAPEDEENFEEAIKNVNTAL
                     NTTQIPSSIEDIFNDDRCINITKQTPSFWILARALKEFVAKEGQGNLPVRGTIPDMIA
                     DSGKYIKLQNVYREKAKKDAAAVGNHVAKLLQSIGQAPESISEKELKLLCSNSAFLRV
                     VRCRSLAEEYGLDTINKDEIISSMDNPDNEIVLYLMLRAVDRFHKQQGRYPGVSNYQV
                     EEDIGKLKSCLTGFLQEYGLSVMVKDDYVHEFCRYGAAEPHTIAAFLGGAAAQEVIKI
                     ITKQFVIFNNTYIYSGMSQTSATFQL"
     exon            131..234
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            235..295
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            296..326
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            327..398
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            399..478
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            479..588
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            589..698
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            699..761
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            762..825
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            826..917
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            918..977
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            978..1111
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1112..1187
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1188..1227
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1228..1314
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1315..1407
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1408..1522
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1523..1572
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1573..1813
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1790..1795
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /note="hexamer: AATAAA"
     polyA_site      1813
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /note="major polyA site"
ORIGIN      
        1 agtgcgcctg cgcgcttgtg gagctggtgg cggcgctccg caggggctcg gctgttttcc
       61 gcgcggcagg cgcggccatg gcgcagctgg gaaagctgct caaggagcag aagtacgacc
      121 ggcagctgag gttgtggggt gatcatgggc aagaggcttt agaatctgct catgtttgcc
      181 taataaatgc aacagccaca ggaactgaaa ttcttaaaaa cttggtacta ccaggtattg
      241 gttcgtttac aattattgat ggaaatcagg tcagcggaga agatgctgga aacaatttct
      301 tccttcaaag aagcagtatc ggcaagaacc gagctgaagc tgccatggaa ttcttacaag
      361 aattaaatag cgatgtctct ggaagttttg tggaagagag tccagaaaac cttctagaca
      421 atgatccctc atttttctgt aggtttactg ttgtagttgc aactcagctt cctgaaagca
      481 cttcactacg cttagcagat gtcctctgga attcccagat tcctcttttg atctgtagga
      541 catatggact agttggttat atgaggatca ttataaaaga acatccagta atagaatctc
      601 atccagataa tgcattagag gatctacgac tagataagcc atttcctgaa ctgagagaac
      661 attttcagtc ctatgatttg gatcatatgg aaaaaaagga ccacagtcat actccatgga
      721 ttgtgatcat agctaaatat ttagcacagt ggtatagtga aacaaatgga cgaataccta
      781 aaacgtataa agaaaaagag gacttcagag atttgattag acaaggaatt ctaaaaaatg
      841 aaaatggggc tccagaagat gaagagaatt ttgaagaagc tattaaaaat gtgaacacag
      901 cactaaatac aactcagatc ccaagcagta ttgaagatat atttaatgat gatcgctgca
      961 taaatatcac caaacagact ccatcatttt ggattttagc tcgtgcctta aaggaatttg
     1021 tggccaaaga gggtcaagga aatttacctg ttcgaggcac aattcctgat atgattgcag
     1081 attcaggcaa atatataaaa ctgcaaaacg tttaccgtga aaaagcaaag aaagatgctg
     1141 ccgctgtggg taatcatgtt gccaaattgc tgcagtccat tggccaggca ccagagtcca
     1201 tttcagagaa agaattaaaa ttactctgca gcaattctgc atttcttcga gtggtaagat
     1261 gtcgatcctt agctgaagaa tatggtttgg atacaattaa caaggatgaa attatttcta
     1321 gcatggacaa tccagataat gaaatagtgt tgtacttaat gttacgggct gttgatagat
     1381 ttcataaaca acagggtaga tatccaggag tatctaacta tcaagttgaa gaagatatag
     1441 gaaagttgaa gtcttgtctc actggcttcc ttcaggaata tggtttatct gtaatggtga
     1501 aagatgatta tgtccacgaa ttttgccgat atggagctgc tgagccacat accattgctg
     1561 cattcttggg gggagctgct gctcaagagg tcatcaaaat aatcaccaaa caatttgtaa
     1621 tttttaataa tacttacatt tacagtggca tgtcacaaac ttcagcaact ttccagttgt
     1681 agagtaagca agcaccttaa gtagtgtgtt aatgattgaa actgtaattg ccttcgggtt
     1741 gtgctttagt ctgtaaaatt ctaaaggaga gctgctaaat tgttttctta ataaacattt
     1801 ttctcatttg taa
//
