LOCUS       NP_003896                534 aa            linear   PRI 27-APR-2025
DEFINITION  NEDD8-activating enzyme E1 regulatory subunit isoform a [Homo
            sapiens].
ACCESSION   NP_003896
VERSION     NP_003896.1
DBSOURCE    REFSEQ: accession 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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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  (residues 1 to 534)
  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 (residues 1 to 534)
  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.
            
            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##
FEATURES             Location/Qualifiers
     source          1..534
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.1"
     Protein         1..534
                     /product="NEDD8-activating enzyme E1 regulatory subunit
                     isoform a"
                     /note="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"
                     /calculated_mol_wt=60115
     Site            2
                     /site_type="acetylation"
                     /note="N-acetylalanine.
                     /evidence=ECO:0007744|PubMed:22814378; propagated from
                     UniProtKB/Swiss-Prot (Q13564.1)"
     Site            6
                     /site_type="acetylation"
                     /note="N6-acetyllysine.
                     /evidence=ECO:0007744|PubMed:19608861; propagated from
                     UniProtKB/Swiss-Prot (Q13564.1)"
     Region          11..532
                     /region_name="APPBP1_RUB"
                     /note="Ubiquitin activating enzyme (E1) subunit APPBP1.
                     APPBP1 is part of the heterodimeric activating enzyme
                     (E1), specific for the Rub family of ubiquitin-like
                     proteins (Ubls). E1 enzymes are part of a conjugation
                     cascade to attach Ub or Ubls, covalently to...; cd01493"
                     /db_xref="CDD:238770"
     Site            order(11..12,14..20,22,44,47..48,51,67..68,70..72,74,81,
                     92,95..96,158,495,499,503,525)
                     /site_type="other"
                     /note="dimer interaction [polypeptide binding]"
                     /db_xref="CDD:238770"
     Site            211
                     /site_type="other"
                     /note="Interaction with UBA3; propagated from
                     UniProtKB/Swiss-Prot (Q13564.1)"
     Region          331..344
                     /region_name="Interaction with UBA3"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13564.1)"
     Site            341
                     /site_type="acetylation"
                     /note="N6-acetyllysine.
                     /evidence=ECO:0000250|UniProtKB:Q8VBW6; propagated from
                     UniProtKB/Swiss-Prot (Q13564.1)"
     CDS             1..534
                     /gene="NAE1"
                     /gene_synonym="A-116A10.1; APPBP1; HPP1; NEDFIH; ula-1"
                     /coded_by="NM_003905.4:78..1682"
                     /note="isoform a is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS10820.1"
                     /db_xref="GeneID:8883"
                     /db_xref="HGNC:HGNC:621"
                     /db_xref="MIM:603385"
ORIGIN      
        1 maqlgkllke qkydrqlrlw gdhgqeales ahvclinata tgteilknlv lpgigsftii
       61 dgnqvsgeda gnnfflqrss igknraeaam eflqelnsdv sgsfveespe nlldndpsff
      121 crftvvvatq lpestslrla dvlwnsqipl licrtyglvg ymriiikehp vieshpdnal
      181 edlrldkpfp elrehfqsyd ldhmekkdhs htpwiviiak ylaqwysetn gripktykek
      241 edfrdlirqg ilknengape deenfeeaik nvntalnttq ipssiedifn ddrcinitkq
      301 tpsfwilara lkefvakegq gnlpvrgtip dmiadsgkyi klqnvyreka kkdaaavgnh
      361 vakllqsigq apesisekel kllcsnsafl rvvrcrslae eygldtinkd eiissmdnpd
      421 neivlylmlr avdrfhkqqg rypgvsnyqv eedigklksc ltgflqeygl svmvkddyvh
      481 efcrygaaep htiaaflgga aaqevikiit kqfvifnnty iysgmsqtsa tfql
//
