ULA1_HUMAN
ID ULA1_HUMAN Reviewed; 534 AA.
AC Q13564; A6NCK0; A6NFN4; A8MU28; B2R700; B3KUP9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=NEDD8-activating enzyme E1 regulatory subunit;
DE AltName: Full=Amyloid beta precursor protein-binding protein 1, 59 kDa;
DE Short=APP-BP1;
DE AltName: Full=Amyloid protein-binding protein 1;
DE AltName: Full=Proto-oncogene protein 1;
GN Name=NAE1; Synonyms=APPBP1; ORFNames=HPP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH APP, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain, and Fetal skeletal muscle;
RX PubMed=8626687; DOI=10.1074/jbc.271.19.11339;
RA Chow N., Korenberg J.R., Chen X.-N., Neve R.L.;
RT "APP-BP1, a novel protein that binds to the carboxyl-terminal region of the
RT amyloid precursor protein.";
RL J. Biol. Chem. 271:11339-11346(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a new human protooncogene.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION.
RX PubMed=10207026; DOI=10.1074/jbc.274.17.12036;
RA Gong L., Yeh E.T.H.;
RT "Identification of the activating and conjugating enzymes of the NEDD8
RT conjugation pathway.";
RL J. Biol. Chem. 274:12036-12042(1999).
RN [10]
RP FUNCTION, AND INTERACTION WITH UBA3.
RX PubMed=10722740; DOI=10.1074/jbc.275.12.8929;
RA Chen Y., McPhie D.L., Hirschberg J., Neve R.L.;
RT "The amyloid precursor protein-binding protein APP-BP1 drives the cell
RT cycle through the S-M checkpoint and causes apoptosis in neurons.";
RL J. Biol. Chem. 275:8929-8935(2000).
RN [11]
RP FUNCTION, AND INTERACTION WITH UBA3.
RX PubMed=12740388; DOI=10.1074/jbc.m303177200;
RA Bohnsack R.N., Haas A.L.;
RT "Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3
RT heterodimer.";
RL J. Biol. Chem. 278:26823-26830(2003).
RN [12]
RP INTERACTION WITH APP, AND SUBCELLULAR LOCATION.
RX PubMed=14557245; DOI=10.1083/jcb.200304003;
RA Chen Y., Liu W., McPhie D.L., Hassinger L., Neve R.L.;
RT "APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased
RT in Alzheimer's disease brain.";
RL J. Cell Biol. 163:27-33(2003).
RN [13]
RP INTERACTION WITH TP53BP2.
RX PubMed=12694406; DOI=10.1046/j.1471-4159.2003.01727.x;
RA Chen Y., Liu W., Naumovski L., Neve R.L.;
RT "ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and
RT decreases APP-BP1-induced cell proliferation and neuronal apoptosis.";
RL J. Neurochem. 85:801-809(2003).
RN [14]
RP UBIQUITINATION.
RX PubMed=18627766; DOI=10.1016/j.bbrc.2008.07.019;
RA Park Y., Yoon S.K., Yoon J.B.;
RT "TRIP12 functions as an E3 ubiquitin ligase of APP-BP1.";
RL Biochem. Biophys. Res. Commun. 374:294-298(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 5-534 IN COMPLEX WITH UBA3; NEDD8
RP AND ATP.
RX PubMed=14690597; DOI=10.1016/s1097-2765(03)00452-0;
RA Walden H., Podgorski M.S., Huang D.T., Miller D.W., Howard R.J.,
RA Minor D.L. Jr., Holton J.M., Schulman B.A.;
RT "The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for
RT selective ubiquitin-like protein activation by an E1.";
RL Mol. Cell 12:1427-1437(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 5-534 IN COMPLEX WITH UBA3, AND
RP MUTAGENESIS OF ASP-331.
RX PubMed=12646924; DOI=10.1038/nature01456;
RA Walden H., Podgorski M.S., Schulman B.A.;
RT "Insights into the ubiquitin transfer cascade from the structure of the
RT activating enzyme for NEDD8.";
RL Nature 422:330-334(2003).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH UBA3 AND UBE2M.
RX PubMed=15361859; DOI=10.1038/nsmb826;
RA Huang D.T., Miller D.W., Mathew R., Cassell R., Holton J.M., Roussel M.F.,
RA Schulman B.A.;
RT "A unique E1-E2 interaction required for optimal conjugation of the
RT ubiquitin-like protein NEDD8.";
RL Nat. Struct. Mol. Biol. 11:927-935(2004).
CC -!- FUNCTION: Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1
CC activates NEDD8 by first adenylating its C-terminal glycine residue
CC with ATP, thereafter linking this residue to the side chain of the
CC catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1
CC finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary
CC for cell cycle progression through the S-M checkpoint. Overexpression
CC of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.
CC {ECO:0000269|PubMed:10207026, ECO:0000269|PubMed:10722740,
CC ECO:0000269|PubMed:12740388}.
CC -!- ACTIVITY REGULATION: Binding of TP53BP2 to the regulatory subunit NAE1
CC decreases neddylation activity.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and
CC UBE2M. Binds APP and TP53BP2. {ECO:0000269|PubMed:12646924,
CC ECO:0000269|PubMed:14690597, ECO:0000269|PubMed:15361859}.
CC -!- INTERACTION:
CC Q13564; P05067: APP; NbExp=3; IntAct=EBI-718631, EBI-77613;
CC Q13564; P07686: HEXB; NbExp=3; IntAct=EBI-718631, EBI-7133736;
CC Q13564; Q8TBC4: UBA3; NbExp=3; IntAct=EBI-718631, EBI-717567;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14557245}.
CC Note=Colocalizes with APP in lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q13564-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13564-2; Sequence=VSP_042895;
CC Name=3;
CC IsoId=Q13564-3; Sequence=VSP_054258;
CC Name=4;
CC IsoId=Q13564-4; Sequence=VSP_054259;
CC -!- TISSUE SPECIFICITY: Ubiquitous in fetal tissues. Expressed throughout
CC the adult brain. {ECO:0000269|PubMed:8626687}.
CC -!- PTM: Ubiquitinated by TRIP12, leading to its degradation by the
CC proteasome. {ECO:0000269|PubMed:18627766}.
CC -!- MISCELLANEOUS: NAE1 and UBA3 correspond to the N-terminal and the C-
CC terminal part of yeast UBA3. In yeast the two subunits form a single
CC polypeptide chain.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. ULA1
CC subfamily. {ECO:0000305}.
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DR EMBL; U50939; AAC50477.1; -; mRNA.
DR EMBL; AY197612; AAP35030.1; -; mRNA.
DR EMBL; AK097680; BAG53511.1; -; mRNA.
DR EMBL; AK298159; BAH12735.1; -; mRNA.
DR EMBL; AK312784; BAG35647.1; -; mRNA.
DR EMBL; AC004638; AAC23784.1; -; Genomic_DNA.
DR EMBL; AC044802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136798; CAB66732.1; -; mRNA.
DR EMBL; CH471092; EAW83042.1; -; Genomic_DNA.
DR EMBL; BC000480; AAH00480.1; -; mRNA.
DR EMBL; BC013301; AAH13301.1; -; mRNA.
DR CCDS; CCDS10820.1; -. [Q13564-1]
DR CCDS; CCDS42171.1; -. [Q13564-2]
DR CCDS; CCDS42172.1; -. [Q13564-3]
DR CCDS; CCDS67050.1; -. [Q13564-4]
DR RefSeq; NP_001018169.1; NM_001018159.1. [Q13564-2]
DR RefSeq; NP_001018170.1; NM_001018160.1. [Q13564-3]
DR RefSeq; NP_001273429.1; NM_001286500.1. [Q13564-4]
DR RefSeq; NP_003896.1; NM_003905.3. [Q13564-1]
DR RefSeq; XP_005256272.1; XM_005256215.1. [Q13564-3]
DR RefSeq; XP_011521724.1; XM_011523422.2.
DR PDB; 1R4M; X-ray; 3.00 A; A/C/E/G=1-534.
DR PDB; 1R4N; X-ray; 3.60 A; A/C/E/G=1-534.
DR PDB; 1TT5; X-ray; 2.60 A; A/C=1-534.
DR PDB; 1YOV; X-ray; 2.60 A; A/C=1-534.
DR PDB; 2NVU; X-ray; 2.80 A; A=1-534.
DR PDB; 3DBH; X-ray; 2.85 A; A/C/E/G=1-534.
DR PDB; 3DBL; X-ray; 2.90 A; A/C/E/G=1-534.
DR PDB; 3DBR; X-ray; 3.05 A; A/C/E/G=1-534.
DR PDB; 3GZN; X-ray; 3.00 A; A/C=1-534.
DR PDBsum; 1R4M; -.
DR PDBsum; 1R4N; -.
DR PDBsum; 1TT5; -.
DR PDBsum; 1YOV; -.
DR PDBsum; 2NVU; -.
DR PDBsum; 3DBH; -.
DR PDBsum; 3DBL; -.
DR PDBsum; 3DBR; -.
DR PDBsum; 3GZN; -.
DR AlphaFoldDB; Q13564; -.
DR SMR; Q13564; -.
DR BioGRID; 114402; 77.
DR CORUM; Q13564; -.
DR IntAct; Q13564; 14.
DR MINT; Q13564; -.
DR STRING; 9606.ENSP00000351990; -.
DR BindingDB; Q13564; -.
DR ChEMBL; CHEMBL2016431; -.
DR DrugBank; DB00171; ATP.
DR GlyGen; Q13564; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13564; -.
DR MetOSite; Q13564; -.
DR PhosphoSitePlus; Q13564; -.
DR SwissPalm; Q13564; -.
DR BioMuta; NAE1; -.
DR DMDM; 50400302; -.
DR EPD; Q13564; -.
DR jPOST; Q13564; -.
DR MassIVE; Q13564; -.
DR MaxQB; Q13564; -.
DR PaxDb; Q13564; -.
DR PeptideAtlas; Q13564; -.
DR PRIDE; Q13564; -.
DR ProteomicsDB; 2076; -.
DR ProteomicsDB; 59567; -. [Q13564-1]
DR ProteomicsDB; 59568; -. [Q13564-2]
DR ProteomicsDB; 840; -.
DR Antibodypedia; 29312; 424 antibodies from 33 providers.
DR DNASU; 8883; -.
DR Ensembl; ENST00000290810.8; ENSP00000290810.3; ENSG00000159593.15. [Q13564-1]
DR Ensembl; ENST00000359087.8; ENSP00000351990.4; ENSG00000159593.15. [Q13564-4]
DR Ensembl; ENST00000379463.6; ENSP00000368776.2; ENSG00000159593.15. [Q13564-2]
DR Ensembl; ENST00000394074.6; ENSP00000377637.2; ENSG00000159593.15. [Q13564-3]
DR GeneID; 8883; -.
DR KEGG; hsa:8883; -.
DR MANE-Select; ENST00000290810.8; ENSP00000290810.3; NM_003905.4; NP_003896.1.
DR UCSC; uc002eqe.4; human. [Q13564-1]
DR CTD; 8883; -.
DR DisGeNET; 8883; -.
DR GeneCards; NAE1; -.
DR HGNC; HGNC:621; NAE1.
DR HPA; ENSG00000159593; Low tissue specificity.
DR MIM; 603385; gene.
DR neXtProt; NX_Q13564; -.
DR OpenTargets; ENSG00000159593; -.
DR PharmGKB; PA162396730; -.
DR VEuPathDB; HostDB:ENSG00000159593; -.
DR eggNOG; KOG2016; Eukaryota.
DR GeneTree; ENSGT00550000074901; -.
DR HOGENOM; CLU_019618_2_1_1; -.
DR InParanoid; Q13564; -.
DR OMA; LHEICRY; -.
DR OrthoDB; 454386at2759; -.
DR PhylomeDB; Q13564; -.
DR TreeFam; TF313972; -.
DR BioCyc; MetaCyc:ENSG00000159593-MON; -.
DR BRENDA; 6.2.1.64; 2681.
DR PathwayCommons; Q13564; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q13564; -.
DR SIGNOR; Q13564; -.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 8883; 570 hits in 1096 CRISPR screens.
DR ChiTaRS; NAE1; human.
DR EvolutionaryTrace; Q13564; -.
DR GeneWiki; APPBP1; -.
DR GenomeRNAi; 8883; -.
DR Pharos; Q13564; Tchem.
DR PRO; PR:Q13564; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q13564; protein.
DR Bgee; ENSG00000159593; Expressed in secondary oocyte and 207 other tissues.
DR ExpressionAtlas; Q13564; baseline and differential.
DR Genevisible; Q13564; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:InterPro.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR030667; APP-BP1.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00899; ThiF; 1.
DR PIRSF; PIRSF039099; APP-BP1; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell cycle;
KW Cell membrane; Membrane; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..534
FT /note="NEDD8-activating enzyme E1 regulatory subunit"
FT /id="PRO_0000194951"
FT REGION 331..344
FT /note="Interaction with UBA3"
FT SITE 211
FT /note="Interaction with UBA3"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 341
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VBW6"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054258"
FT VAR_SEQ 1..17
FT /note="MAQLGKLLKEQKYDRQL -> MDAQQTKTNEA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042895"
FT VAR_SEQ 53
FT /note="G -> GNVG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054259"
FT VARIANT 101
FT /note="S -> F (in dbSNP:rs363212)"
FT /id="VAR_052435"
FT MUTAGEN 331
FT /note="D->A: Impairs the formation of the NEDD8-UBA3
FT thioester."
FT /evidence="ECO:0000269|PubMed:12646924"
FT CONFLICT 268
FT /note="A -> V (in Ref. 3; BAG53511)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="I -> T (in Ref. 3; BAG53511)"
FT /evidence="ECO:0000305"
FT HELIX 3..12
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 14..30
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 40..50
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 85..94
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 117..122
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 133..145
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 190..197
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:1YOV"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 236..249
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:1YOV"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 283..289
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:3DBR"
FT HELIX 303..316
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 317..321
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 336..366
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 377..385
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 398..402
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 404..406
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 409..415
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 423..439
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 450..467
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 476..484
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 485..487
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 491..510
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 520..523
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 524..527
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:1TT5"
SQ SEQUENCE 534 AA; 60246 MW; 5EC8D3ACE6374F21 CRC64;
MAQLGKLLKE QKYDRQLRLW GDHGQEALES AHVCLINATA TGTEILKNLV LPGIGSFTII
DGNQVSGEDA GNNFFLQRSS IGKNRAEAAM EFLQELNSDV SGSFVEESPE NLLDNDPSFF
CRFTVVVATQ LPESTSLRLA DVLWNSQIPL LICRTYGLVG YMRIIIKEHP VIESHPDNAL
EDLRLDKPFP ELREHFQSYD LDHMEKKDHS HTPWIVIIAK YLAQWYSETN GRIPKTYKEK
EDFRDLIRQG ILKNENGAPE DEENFEEAIK NVNTALNTTQ IPSSIEDIFN DDRCINITKQ
TPSFWILARA LKEFVAKEGQ GNLPVRGTIP DMIADSGKYI KLQNVYREKA KKDAAAVGNH
VAKLLQSIGQ APESISEKEL KLLCSNSAFL RVVRCRSLAE EYGLDTINKD EIISSMDNPD
NEIVLYLMLR AVDRFHKQQG RYPGVSNYQV EEDIGKLKSC LTGFLQEYGL SVMVKDDYVH
EFCRYGAAEP HTIAAFLGGA AAQEVIKIIT KQFVIFNNTY IYSGMSQTSA TFQL
