Full text data of UBA3
UBA3
(UBE1C)
[Confidence: low (only semi-automatic identification from reviews)]
NEDD8-activating enzyme E1 catalytic subunit; 6.3.2.- (NEDD8-activating enzyme E1C; Ubiquitin-activating enzyme E1C; Ubiquitin-like modifier-activating enzyme 3; Ubiquitin-activating enzyme 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
NEDD8-activating enzyme E1 catalytic subunit; 6.3.2.- (NEDD8-activating enzyme E1C; Ubiquitin-activating enzyme E1C; Ubiquitin-like modifier-activating enzyme 3; Ubiquitin-activating enzyme 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q8TBC4
ID UBA3_HUMAN Reviewed; 463 AA.
AC Q8TBC4; A6NLB5; A8K027; O76088; Q9NTU3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-DEC-2005, sequence version 2.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=NEDD8-activating enzyme E1 catalytic subunit;
DE EC=6.3.2.-;
DE AltName: Full=NEDD8-activating enzyme E1C;
DE AltName: Full=Ubiquitin-activating enzyme E1C;
DE AltName: Full=Ubiquitin-like modifier-activating enzyme 3;
DE Short=Ubiquitin-activating enzyme 3;
GN Name=UBA3; Synonyms=UBE1C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal kidney;
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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-9.
RC TISSUE=Prostatic adenocarcinoma;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-463 (ISOFORM 1), VARIANT ARG-9,
RP FUNCTION, MUTAGENESIS OF CYS-237, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-463, AND FUNCTION.
RX PubMed=9694792;
RA Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S.,
RA Tanaka K., Kato S.;
RT "A new NEDD8-ligating system for cullin-4A.";
RL Genes Dev. 12:2263-2268(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH NAE1.
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
RT AppBp1-Uba3 heterodimer.";
RL J. Biol. Chem. 278:26823-26830(2003).
RN [9]
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.,
RA Buerckstuemmer T., 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 33-463 IN COMPLEX WITH NAE1;
RP NEDD8 AND ATP, AND MUTAGENESIS OF ARG-211.
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
RT for selective ubiquitin-like protein activation by an E1.";
RL Mol. Cell 12:1427-1437(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-463 IN COMPLEX WITH NAE1,
RP AND MUTAGENESIS OF ILE-148; ASP-167; 227-LEU-TYR-228; THR-238; ILE-310
RP AND 352-TYR--TYR-357.
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
RT the activating enzyme for NEDD8.";
RL Nature 422:330-334(2003).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 33-463 IN COMPLEX WITH NAE1
RP AND UBE2M, AND MUTAGENESIS OF PHE-65; 160-HIS-ILE-161; PRO-192;
RP ILE-195; PRO-197; LEU-214; MET-217 AND ILE-331.
RX PubMed=15361859; DOI=10.1038/nsmb826;
RA Huang D.T., Miller D.W., Mathew R., Cassell R., Holton J.M.,
RA Roussel M.F., 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).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 368-463 IN COMPLEX WITH
RP UBE2M, AND MUTAGENESIS OF SER-368; GLN-369; LEU-370; THR-412; LEU-415;
RP VAL-418; ILE-421 AND ARG-424.
RX PubMed=15694336; DOI=10.1016/j.molcel.2004.12.020;
RA Huang D.T., Paydar A., Zhuang M., Waddell M.B., Holton J.M.,
RA Schulman B.A.;
RT "Structural basis for recruitment of Ubc12 by an E2 binding domain in
RT NEDD8's E1.";
RL Mol. Cell 17:341-350(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 368-420 IN COMPLEX WITH
RP UBE2F.
RX PubMed=19250909; DOI=10.1016/j.molcel.2009.01.011;
RA Huang D.T., Ayrault O., Hunt H.W., Taherbhoy A.M., Duda D.M.,
RA Scott D.C., Borg L.A., Neale G., Murray P.J., Roussel M.F.,
RA Schulman B.A.;
RT "E2-RING expansion of the NEDD8 cascade confers specificity to cullin
RT modification.";
RL Mol. Cell 33:483-495(2009).
CC -!- FUNCTION: Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1
CC activates NEDD8 by first adenylating its C-terminal glycine
CC residue with ATP, thereafter linking this residue to the side
CC chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester
CC and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine
CC of UBE2M. Down-regulates steroid receptor activity. Necessary for
CC cell cycle progression.
CC -!- ENZYME REGULATION: Binding of TP53BP2 to the regulatory subunit
CC NAE1 decreases activity.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F
CC and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By
CC similarity). Interacts with TBATA (By similarity).
CC -!- INTERACTION:
CC P54727:RAD23B; NbExp=2; IntAct=EBI-717567, EBI-954531;
CC P61081:UBE2M; NbExp=2; IntAct=EBI-717567, EBI-1041660;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TBC4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TBC4-2; Sequence=VSP_041127;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- MISCELLANEOUS: Arg-211 acts as a selectivity gate, preventing
CC misactivation of ubiquitin by this NEDD8-specific E1 complex.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA3
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC27648.1; Type=Erroneous initiation;
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DR EMBL; AL117566; CAB55996.2; -; mRNA.
DR EMBL; AK002159; BAG51021.1; -; mRNA.
DR EMBL; AK289392; BAF82081.1; -; mRNA.
DR EMBL; AC092060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65470.1; -; Genomic_DNA.
DR EMBL; BC022853; AAH22853.1; -; mRNA.
DR EMBL; AF046024; AAC27648.1; ALT_INIT; mRNA.
DR EMBL; AB012190; BAA33144.1; -; mRNA.
DR PIR; T17306; T17306.
DR RefSeq; NP_003959.3; NM_003968.3.
DR RefSeq; NP_937838.1; NM_198195.1.
DR UniGene; Hs.154320; -.
DR PDB; 1R4M; X-ray; 3.00 A; B/D/F/H=33-463.
DR PDB; 1R4N; X-ray; 3.60 A; B/D/F/H=33-463.
DR PDB; 1TT5; X-ray; 2.60 A; B/D=33-463.
DR PDB; 1Y8X; X-ray; 2.40 A; B=368-463.
DR PDB; 1YOV; X-ray; 2.60 A; B/D=22-463.
DR PDB; 2LQ7; NMR; -; A=368-463.
DR PDB; 2NVU; X-ray; 2.80 A; B=33-463.
DR PDB; 3DBH; X-ray; 2.85 A; B/D/F/H=33-463.
DR PDB; 3DBL; X-ray; 2.90 A; B/D/F/H=33-463.
DR PDB; 3DBR; X-ray; 3.05 A; B/D/F/H=33-463.
DR PDB; 3FN1; X-ray; 2.50 A; A=368-463.
DR PDB; 3GZN; X-ray; 3.00 A; B/D=1-463.
DR PDBsum; 1R4M; -.
DR PDBsum; 1R4N; -.
DR PDBsum; 1TT5; -.
DR PDBsum; 1Y8X; -.
DR PDBsum; 1YOV; -.
DR PDBsum; 2LQ7; -.
DR PDBsum; 2NVU; -.
DR PDBsum; 3DBH; -.
DR PDBsum; 3DBL; -.
DR PDBsum; 3DBR; -.
DR PDBsum; 3FN1; -.
DR PDBsum; 3GZN; -.
DR ProteinModelPortal; Q8TBC4; -.
DR SMR; Q8TBC4; 33-463.
DR IntAct; Q8TBC4; 11.
DR MINT; MINT-1375257; -.
DR STRING; 9606.ENSP00000354340; -.
DR ChEMBL; CHEMBL2016430; -.
DR PhosphoSite; Q8TBC4; -.
DR DMDM; 83305811; -.
DR PaxDb; Q8TBC4; -.
DR PRIDE; Q8TBC4; -.
DR DNASU; 9039; -.
DR Ensembl; ENST00000349511; ENSP00000340041; ENSG00000144744.
DR Ensembl; ENST00000361055; ENSP00000354340; ENSG00000144744.
DR GeneID; 9039; -.
DR KEGG; hsa:9039; -.
DR UCSC; uc003dno.3; human.
DR CTD; 9039; -.
DR GeneCards; GC03M069103; -.
DR HGNC; HGNC:12470; UBA3.
DR HPA; HPA034873; -.
DR MIM; 603172; gene.
DR neXtProt; NX_Q8TBC4; -.
DR PharmGKB; PA162407622; -.
DR eggNOG; COG0476; -.
DR HOGENOM; HOG000166793; -.
DR HOVERGEN; HBG082736; -.
DR InParanoid; Q8TBC4; -.
DR KO; K10686; -.
DR OMA; DHIQWIF; -.
DR PhylomeDB; Q8TBC4; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00885; -.
DR ChiTaRS; UBA3; human.
DR EvolutionaryTrace; Q8TBC4; -.
DR GeneWiki; UBE1C; -.
DR GenomeRNAi; 9039; -.
DR NextBio; 33859; -.
DR PRO; PR:Q8TBC4; -.
DR ArrayExpress; Q8TBC4; -.
DR Bgee; Q8TBC4; -.
DR CleanEx; HS_UBA3; -.
DR Genevestigator; Q8TBC4; -.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:Ensembl.
DR GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
DR GO; GO:0007113; P:endomitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0045116; P:protein neddylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR Gene3D; 1.10.10.520; -; 1.
DR Gene3D; 3.10.20.260; -; 1.
DR Gene3D; 3.40.50.720; -; 2.
DR InterPro; IPR014929; E2_binding.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR023318; Ub_act_enz_dom_a.
DR InterPro; IPR000127; UBact_repeat.
DR InterPro; IPR019572; Ubiquitin-activating_enzyme.
DR InterPro; IPR018074; UBQ-activ_enz_E1_AS.
DR Pfam; PF08825; E2_bind; 1.
DR Pfam; PF00899; ThiF; 1.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR Pfam; PF02134; UBACT; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS00536; UBIQUITIN_ACTIVAT_1; FALSE_NEG.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell cycle; Complete proteome; Ligase; Nucleotide-binding;
KW Polymorphism; Reference proteome; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 463 NEDD8-activating enzyme E1 catalytic
FT subunit.
FT /FTId=PRO_0000194941.
FT NP_BIND 100 124 ATP.
FT NP_BIND 148 171 ATP.
FT REGION 53 70 Interaction with UBE2M N-terminus.
FT REGION 157 161 Interaction with UBE2M N-terminus.
FT REGION 192 217 Interaction with UBE2M N-terminus.
FT REGION 227 229 Interaction with NEDD8.
FT REGION 242 248 Interaction with NAE1.
FT REGION 292 295 Interaction with NAE1.
FT REGION 331 338 Interaction with UBE2M N-terminus.
FT REGION 352 357 Interaction with NEDD8.
FT REGION 368 463 Interaction with UBE2M core domain.
FT ACT_SITE 237 237 Glycyl thioester intermediate.
FT SITE 211 211 Determines specificity for NEDD8.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 8 21 Missing (in isoform 2).
FT /FTId=VSP_041127.
FT VARIANT 9 9 K -> R (in dbSNP:rs17852113).
FT /FTId=VAR_023945.
FT MUTAGEN 65 65 F->G: Reduces affinity for UBE2M.
FT MUTAGEN 148 148 I->A: No effect on NEDD8 adenylation.
FT MUTAGEN 160 161 HI->AA: Reduces affinity for UBE2M.
FT MUTAGEN 167 167 D->A: Abolishes NEDD8 adenylation.
FT MUTAGEN 192 192 P->A: Reduces affinity for UBE2M; when
FT associated with A-195 and A-197.
FT MUTAGEN 195 195 I->A: Reduces affinity for UBE2M; when
FT associated with A-192 and A-197.
FT MUTAGEN 197 197 P->A: Reduces affinity for UBE2M; when
FT associated with A-192 and A-195.
FT MUTAGEN 211 211 R->Q: Abolishes specificity for NEDD8.
FT MUTAGEN 214 214 L->A: Reduces affinity for UBE2M; when
FT associated with A-217.
FT MUTAGEN 217 217 M->A: Reduces affinity for UBE2M; when
FT associated with A-214.
FT MUTAGEN 227 228 LY->DD: Strongly reduces NEDD8
FT adenylation.
FT MUTAGEN 237 237 C->S: Abolishes thioester intermediate
FT formation.
FT MUTAGEN 238 238 T->A: No effect on NEDD8 adenylation;
FT impairs thioester intermediate formation.
FT MUTAGEN 310 310 I->A: No effect on NEDD8 adenylation or
FT thioester intermediate formation; impairs
FT NEDD8 transfer to UBE2M.
FT MUTAGEN 331 331 I->A: Reduces affinity for UBE2M.
FT MUTAGEN 352 357 YTYTFE->ATATA: Abolishes NEDD8
FT adenylation.
FT MUTAGEN 368 368 S->P: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 369 369 Q->P: No effect on NEDD8 transfer to
FT UBE2M.
FT MUTAGEN 370 370 L->P: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 412 412 T->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 415 415 L->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 418 418 V->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 421 421 I->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 424 424 R->A: No effect on NEDD8 transfer to
FT UBE2M.
FT CONFLICT 146 146 N -> Y (in Ref. 1; CAB55996).
FT CONFLICT 271 271 D -> G (in Ref. 1; CAB55996).
FT TURN 35 38
FT HELIX 39 46
FT HELIX 62 68
FT STRAND 72 75
FT HELIX 80 90
FT STRAND 96 100
FT HELIX 106 108
FT TURN 109 111
FT HELIX 117 119
FT HELIX 124 135
FT STRAND 142 146
FT HELIX 148 150
FT HELIX 153 156
FT STRAND 160 164
FT HELIX 169 181
FT STRAND 185 188
FT STRAND 189 191
FT HELIX 192 194
FT STRAND 198 204
FT STRAND 207 213
FT TURN 215 217
FT HELIX 221 227
FT HELIX 236 241
FT HELIX 246 255
FT HELIX 257 260
FT HELIX 275 291
FT HELIX 299 306
FT HELIX 314 333
FT STRAND 341 346
FT STRAND 348 350
FT STRAND 352 356
FT TURN 365 367
FT STRAND 372 376
FT STRAND 377 379
FT HELIX 382 391
FT TURN 393 395
FT STRAND 401 406
FT STRAND 409 414
FT HELIX 419 430
FT STRAND 431 433
FT HELIX 434 436
FT HELIX 437 440
FT STRAND 443 447
FT STRAND 451 453
FT STRAND 455 460
SQ SEQUENCE 463 AA; 51852 MW; 4C16DC0EEDE31A76 CRC64;
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST
ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDI
GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI
SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA
SMPRLPEHCI EYVRMLQWPK EQPFGEGVPL DGDDPEHIQW IFQKSLERAS QYNIRGVTYR
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER
KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS
IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FTS
//
ID UBA3_HUMAN Reviewed; 463 AA.
AC Q8TBC4; A6NLB5; A8K027; O76088; Q9NTU3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-DEC-2005, sequence version 2.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=NEDD8-activating enzyme E1 catalytic subunit;
DE EC=6.3.2.-;
DE AltName: Full=NEDD8-activating enzyme E1C;
DE AltName: Full=Ubiquitin-activating enzyme E1C;
DE AltName: Full=Ubiquitin-like modifier-activating enzyme 3;
DE Short=Ubiquitin-activating enzyme 3;
GN Name=UBA3; Synonyms=UBE1C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal kidney;
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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-9.
RC TISSUE=Prostatic adenocarcinoma;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-463 (ISOFORM 1), VARIANT ARG-9,
RP FUNCTION, MUTAGENESIS OF CYS-237, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-463, AND FUNCTION.
RX PubMed=9694792;
RA Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S.,
RA Tanaka K., Kato S.;
RT "A new NEDD8-ligating system for cullin-4A.";
RL Genes Dev. 12:2263-2268(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH NAE1.
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
RT AppBp1-Uba3 heterodimer.";
RL J. Biol. Chem. 278:26823-26830(2003).
RN [9]
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.,
RA Buerckstuemmer T., 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 33-463 IN COMPLEX WITH NAE1;
RP NEDD8 AND ATP, AND MUTAGENESIS OF ARG-211.
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
RT for selective ubiquitin-like protein activation by an E1.";
RL Mol. Cell 12:1427-1437(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-463 IN COMPLEX WITH NAE1,
RP AND MUTAGENESIS OF ILE-148; ASP-167; 227-LEU-TYR-228; THR-238; ILE-310
RP AND 352-TYR--TYR-357.
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
RT the activating enzyme for NEDD8.";
RL Nature 422:330-334(2003).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 33-463 IN COMPLEX WITH NAE1
RP AND UBE2M, AND MUTAGENESIS OF PHE-65; 160-HIS-ILE-161; PRO-192;
RP ILE-195; PRO-197; LEU-214; MET-217 AND ILE-331.
RX PubMed=15361859; DOI=10.1038/nsmb826;
RA Huang D.T., Miller D.W., Mathew R., Cassell R., Holton J.M.,
RA Roussel M.F., 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).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 368-463 IN COMPLEX WITH
RP UBE2M, AND MUTAGENESIS OF SER-368; GLN-369; LEU-370; THR-412; LEU-415;
RP VAL-418; ILE-421 AND ARG-424.
RX PubMed=15694336; DOI=10.1016/j.molcel.2004.12.020;
RA Huang D.T., Paydar A., Zhuang M., Waddell M.B., Holton J.M.,
RA Schulman B.A.;
RT "Structural basis for recruitment of Ubc12 by an E2 binding domain in
RT NEDD8's E1.";
RL Mol. Cell 17:341-350(2005).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 368-420 IN COMPLEX WITH
RP UBE2F.
RX PubMed=19250909; DOI=10.1016/j.molcel.2009.01.011;
RA Huang D.T., Ayrault O., Hunt H.W., Taherbhoy A.M., Duda D.M.,
RA Scott D.C., Borg L.A., Neale G., Murray P.J., Roussel M.F.,
RA Schulman B.A.;
RT "E2-RING expansion of the NEDD8 cascade confers specificity to cullin
RT modification.";
RL Mol. Cell 33:483-495(2009).
CC -!- FUNCTION: Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1
CC activates NEDD8 by first adenylating its C-terminal glycine
CC residue with ATP, thereafter linking this residue to the side
CC chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester
CC and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine
CC of UBE2M. Down-regulates steroid receptor activity. Necessary for
CC cell cycle progression.
CC -!- ENZYME REGULATION: Binding of TP53BP2 to the regulatory subunit
CC NAE1 decreases activity.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F
CC and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By
CC similarity). Interacts with TBATA (By similarity).
CC -!- INTERACTION:
CC P54727:RAD23B; NbExp=2; IntAct=EBI-717567, EBI-954531;
CC P61081:UBE2M; NbExp=2; IntAct=EBI-717567, EBI-1041660;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TBC4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TBC4-2; Sequence=VSP_041127;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- MISCELLANEOUS: Arg-211 acts as a selectivity gate, preventing
CC misactivation of ubiquitin by this NEDD8-specific E1 complex.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA3
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC27648.1; Type=Erroneous initiation;
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DR EMBL; AL117566; CAB55996.2; -; mRNA.
DR EMBL; AK002159; BAG51021.1; -; mRNA.
DR EMBL; AK289392; BAF82081.1; -; mRNA.
DR EMBL; AC092060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65470.1; -; Genomic_DNA.
DR EMBL; BC022853; AAH22853.1; -; mRNA.
DR EMBL; AF046024; AAC27648.1; ALT_INIT; mRNA.
DR EMBL; AB012190; BAA33144.1; -; mRNA.
DR PIR; T17306; T17306.
DR RefSeq; NP_003959.3; NM_003968.3.
DR RefSeq; NP_937838.1; NM_198195.1.
DR UniGene; Hs.154320; -.
DR PDB; 1R4M; X-ray; 3.00 A; B/D/F/H=33-463.
DR PDB; 1R4N; X-ray; 3.60 A; B/D/F/H=33-463.
DR PDB; 1TT5; X-ray; 2.60 A; B/D=33-463.
DR PDB; 1Y8X; X-ray; 2.40 A; B=368-463.
DR PDB; 1YOV; X-ray; 2.60 A; B/D=22-463.
DR PDB; 2LQ7; NMR; -; A=368-463.
DR PDB; 2NVU; X-ray; 2.80 A; B=33-463.
DR PDB; 3DBH; X-ray; 2.85 A; B/D/F/H=33-463.
DR PDB; 3DBL; X-ray; 2.90 A; B/D/F/H=33-463.
DR PDB; 3DBR; X-ray; 3.05 A; B/D/F/H=33-463.
DR PDB; 3FN1; X-ray; 2.50 A; A=368-463.
DR PDB; 3GZN; X-ray; 3.00 A; B/D=1-463.
DR PDBsum; 1R4M; -.
DR PDBsum; 1R4N; -.
DR PDBsum; 1TT5; -.
DR PDBsum; 1Y8X; -.
DR PDBsum; 1YOV; -.
DR PDBsum; 2LQ7; -.
DR PDBsum; 2NVU; -.
DR PDBsum; 3DBH; -.
DR PDBsum; 3DBL; -.
DR PDBsum; 3DBR; -.
DR PDBsum; 3FN1; -.
DR PDBsum; 3GZN; -.
DR ProteinModelPortal; Q8TBC4; -.
DR SMR; Q8TBC4; 33-463.
DR IntAct; Q8TBC4; 11.
DR MINT; MINT-1375257; -.
DR STRING; 9606.ENSP00000354340; -.
DR ChEMBL; CHEMBL2016430; -.
DR PhosphoSite; Q8TBC4; -.
DR DMDM; 83305811; -.
DR PaxDb; Q8TBC4; -.
DR PRIDE; Q8TBC4; -.
DR DNASU; 9039; -.
DR Ensembl; ENST00000349511; ENSP00000340041; ENSG00000144744.
DR Ensembl; ENST00000361055; ENSP00000354340; ENSG00000144744.
DR GeneID; 9039; -.
DR KEGG; hsa:9039; -.
DR UCSC; uc003dno.3; human.
DR CTD; 9039; -.
DR GeneCards; GC03M069103; -.
DR HGNC; HGNC:12470; UBA3.
DR HPA; HPA034873; -.
DR MIM; 603172; gene.
DR neXtProt; NX_Q8TBC4; -.
DR PharmGKB; PA162407622; -.
DR eggNOG; COG0476; -.
DR HOGENOM; HOG000166793; -.
DR HOVERGEN; HBG082736; -.
DR InParanoid; Q8TBC4; -.
DR KO; K10686; -.
DR OMA; DHIQWIF; -.
DR PhylomeDB; Q8TBC4; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00885; -.
DR ChiTaRS; UBA3; human.
DR EvolutionaryTrace; Q8TBC4; -.
DR GeneWiki; UBE1C; -.
DR GenomeRNAi; 9039; -.
DR NextBio; 33859; -.
DR PRO; PR:Q8TBC4; -.
DR ArrayExpress; Q8TBC4; -.
DR Bgee; Q8TBC4; -.
DR CleanEx; HS_UBA3; -.
DR Genevestigator; Q8TBC4; -.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:Ensembl.
DR GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
DR GO; GO:0007113; P:endomitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0045116; P:protein neddylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR Gene3D; 1.10.10.520; -; 1.
DR Gene3D; 3.10.20.260; -; 1.
DR Gene3D; 3.40.50.720; -; 2.
DR InterPro; IPR014929; E2_binding.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR023318; Ub_act_enz_dom_a.
DR InterPro; IPR000127; UBact_repeat.
DR InterPro; IPR019572; Ubiquitin-activating_enzyme.
DR InterPro; IPR018074; UBQ-activ_enz_E1_AS.
DR Pfam; PF08825; E2_bind; 1.
DR Pfam; PF00899; ThiF; 1.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR Pfam; PF02134; UBACT; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS00536; UBIQUITIN_ACTIVAT_1; FALSE_NEG.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell cycle; Complete proteome; Ligase; Nucleotide-binding;
KW Polymorphism; Reference proteome; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 463 NEDD8-activating enzyme E1 catalytic
FT subunit.
FT /FTId=PRO_0000194941.
FT NP_BIND 100 124 ATP.
FT NP_BIND 148 171 ATP.
FT REGION 53 70 Interaction with UBE2M N-terminus.
FT REGION 157 161 Interaction with UBE2M N-terminus.
FT REGION 192 217 Interaction with UBE2M N-terminus.
FT REGION 227 229 Interaction with NEDD8.
FT REGION 242 248 Interaction with NAE1.
FT REGION 292 295 Interaction with NAE1.
FT REGION 331 338 Interaction with UBE2M N-terminus.
FT REGION 352 357 Interaction with NEDD8.
FT REGION 368 463 Interaction with UBE2M core domain.
FT ACT_SITE 237 237 Glycyl thioester intermediate.
FT SITE 211 211 Determines specificity for NEDD8.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 8 21 Missing (in isoform 2).
FT /FTId=VSP_041127.
FT VARIANT 9 9 K -> R (in dbSNP:rs17852113).
FT /FTId=VAR_023945.
FT MUTAGEN 65 65 F->G: Reduces affinity for UBE2M.
FT MUTAGEN 148 148 I->A: No effect on NEDD8 adenylation.
FT MUTAGEN 160 161 HI->AA: Reduces affinity for UBE2M.
FT MUTAGEN 167 167 D->A: Abolishes NEDD8 adenylation.
FT MUTAGEN 192 192 P->A: Reduces affinity for UBE2M; when
FT associated with A-195 and A-197.
FT MUTAGEN 195 195 I->A: Reduces affinity for UBE2M; when
FT associated with A-192 and A-197.
FT MUTAGEN 197 197 P->A: Reduces affinity for UBE2M; when
FT associated with A-192 and A-195.
FT MUTAGEN 211 211 R->Q: Abolishes specificity for NEDD8.
FT MUTAGEN 214 214 L->A: Reduces affinity for UBE2M; when
FT associated with A-217.
FT MUTAGEN 217 217 M->A: Reduces affinity for UBE2M; when
FT associated with A-214.
FT MUTAGEN 227 228 LY->DD: Strongly reduces NEDD8
FT adenylation.
FT MUTAGEN 237 237 C->S: Abolishes thioester intermediate
FT formation.
FT MUTAGEN 238 238 T->A: No effect on NEDD8 adenylation;
FT impairs thioester intermediate formation.
FT MUTAGEN 310 310 I->A: No effect on NEDD8 adenylation or
FT thioester intermediate formation; impairs
FT NEDD8 transfer to UBE2M.
FT MUTAGEN 331 331 I->A: Reduces affinity for UBE2M.
FT MUTAGEN 352 357 YTYTFE->ATATA: Abolishes NEDD8
FT adenylation.
FT MUTAGEN 368 368 S->P: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 369 369 Q->P: No effect on NEDD8 transfer to
FT UBE2M.
FT MUTAGEN 370 370 L->P: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 412 412 T->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 415 415 L->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 418 418 V->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 421 421 I->A: Impairs NEDD8 transfer to UBE2M.
FT MUTAGEN 424 424 R->A: No effect on NEDD8 transfer to
FT UBE2M.
FT CONFLICT 146 146 N -> Y (in Ref. 1; CAB55996).
FT CONFLICT 271 271 D -> G (in Ref. 1; CAB55996).
FT TURN 35 38
FT HELIX 39 46
FT HELIX 62 68
FT STRAND 72 75
FT HELIX 80 90
FT STRAND 96 100
FT HELIX 106 108
FT TURN 109 111
FT HELIX 117 119
FT HELIX 124 135
FT STRAND 142 146
FT HELIX 148 150
FT HELIX 153 156
FT STRAND 160 164
FT HELIX 169 181
FT STRAND 185 188
FT STRAND 189 191
FT HELIX 192 194
FT STRAND 198 204
FT STRAND 207 213
FT TURN 215 217
FT HELIX 221 227
FT HELIX 236 241
FT HELIX 246 255
FT HELIX 257 260
FT HELIX 275 291
FT HELIX 299 306
FT HELIX 314 333
FT STRAND 341 346
FT STRAND 348 350
FT STRAND 352 356
FT TURN 365 367
FT STRAND 372 376
FT STRAND 377 379
FT HELIX 382 391
FT TURN 393 395
FT STRAND 401 406
FT STRAND 409 414
FT HELIX 419 430
FT STRAND 431 433
FT HELIX 434 436
FT HELIX 437 440
FT STRAND 443 447
FT STRAND 451 453
FT STRAND 455 460
SQ SEQUENCE 463 AA; 51852 MW; 4C16DC0EEDE31A76 CRC64;
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST
ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDI
GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI
SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA
SMPRLPEHCI EYVRMLQWPK EQPFGEGVPL DGDDPEHIQW IFQKSLERAS QYNIRGVTYR
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER
KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS
IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FTS
//
MIM
603172
*RECORD*
*FIELD* NO
603172
*FIELD* TI
*603172 UBIQUITIN-ACTIVATING ENZYME E1C; UBE1C
;;UBIQUITIN-ACTIVATING ENZYME 3, S. CEREVISIAE, HOMOLOG OF; UBA3
read more*FIELD* TX
CLONING
Ubiquitin (191339) is covalently attached to target proteins by a
multienzymatic system consisting of E1 (ubiquitin-activating), E2
(ubiquitin-conjugating), and E3 (ubiquitin-ligating) enzymes. Osaka et
al. (1998) found that NEDD8 (603171), a ubiquitin-like protein, is
conjugated to proteins in a manner analogous to ubiquitylation. They
found that beta-amyloid precursor protein-binding protein-1 (APPBP1;
603385) can bind to NEDD8 in rabbit reticulocyte lysates. However, since
APPBP1 shows similarity to only the N-terminal domain of an E1 enzyme,
the authors reasoned that it must interact with a protein showing
similarity to the C-terminal region of E1s. By searching sequence
databases, Osaka et al. (1998) identified cDNAs encoding UBA3, the human
homolog of yeast Uba3. The predicted 442-amino acid UBA3 protein shares
43% sequence identity with yeast Uba3. In vitro, UBA3 formed a complex
with APPBP1 and a thioester linkage with NEDD8. Osaka et al. (1998)
suggested that the APPBP1/UBA3 complex functions as an E1-like enzyme
for the activation of NEDD8.
To identify novel steroid receptor-interacting proteins, Fan et al.
(2002) performed yeast 2-hybrid screening of a rat uterine luminal
epithelium cDNA library using the ligand-binding and hinge region of
ER-alpha (133430) as bait. They cloned and characterized a cDNA encoding
a protein homologous to yeast and human UBA3, the catalytic subunit of
the activating enzyme of the ubiquitin-like NEDD8 conjugation pathway
(known as neddylation). Sequence analysis revealed that Uba3 contains
multiple nuclear receptor (NR)-interacting motifs (NR boxes), which are
known to mediate interactions between coregulatory proteins and
ligand-activated NRs. Yeast 2-hybrid and glutathione-S-transferase
pull-down assays demonstrated that Uba3 directly interacts with
ligand-occupied ER-alpha and ER-beta (601663). Transient transfection of
Uba3 in mammalian cells inhibited ER-mediated transactivation in a
time-dependent fashion. The authors concluded that UBA3 inhibits
transcription induced by steroid hormone receptors through a novel
mechanism that involves the neddylation pathway.
GENE FUNCTION
The NEDD8-activating enzyme, or NAE, composed of NAE1 (603385) and UBA3
subunits, is an essential component of the NEDD8 contribution pathway
that controls the activity of the cullin-RING subtype of ubiquitin
ligases, thereby regulating the turnover of a subset of proteins
upstream of the proteasome. Substrates of cullin-RING ligases have
important roles in cellular processes associated with cancer cell growth
and survival pathways. Soucy et al. (2009) described MLN4924, a potent
and selective inhibitor of NAE. MLN4924 disrupts cullin-RING
ligase-mediated protein turnover leading to apoptotic death in human
tumor cells by a new mechanism of action, the deregulation of S-phase
DNA synthesis. MLN4924 suppressed the growth of human tumor xenografts
in mice at compound exposures that were well tolerated. Soucy et al.
(2009) concluded that NAE inhibitors may hold promise for the treatment
of cancer.
BIOCHEMICAL FEATURES
Walden et al. (2003) reported the structure and mutational analysis of
human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8. Each E1
activity is specified by a domain: an adenylation domain resembling
bacterial adenylating enzymes, an E1-specific domain organized around
the catalytic cysteine, and a domain involved in E2 recognition
resembling ubiquitin. The domains are arranged around 2 clefts that
coordinate protein and nucleotide binding so that each of E1's reactions
drives the next, in an assembly-line fashion.
Bohnsack and Haas (2003) purified APPBP1-UBA3 from human erythrocytes
and analyzed the kinetics of NEDD8 activation. In the presence of
radiolabeled ATP and radiolabeled recombinant NEDD8, APPBP1-UBA3 rapidly
formed a stable stoichiometric ternary complex composed of tightly bound
NEDD8 adenylate and UBA3-NEDD8 thiol ester. Isotope exchange kinetics
showed that the heterodimer followed a pseudo-ordered mechanism with ATP
the leading and NEDD8 the trailing substrate. Ala72 of NEDD8 was
critical in binding APPBP1-UBA3. Bohnsack and Haas (2003) concluded that
the mechanism of NEDD8 activation by APPBP1-UBA3 shows a high degree of
conservation with ubiquitin activation by UBA1.
Huang et al. (2007) reported the structural analysis of a trapped
ubiquitin-like protein (UBL) activation complex for the human NEDD8
pathway containing NEDD8's heterodimeric E1 (APPBP1-UBA3), 2 NEDD8s (1
thioester-linked to E1, 1 noncovalently associated for adenylation), a
catalytically inactive E2 (UBC12; 603173), and MgATP. The results
suggested that a thioester switch toggles E1-E2 affinities. Two E2
binding sites depend on NEDD8 being thioester-linked to E1. One is
unmasked by a striking E1 conformational change. The other comes
directly from the thioester-bound NEDD8. After NEDD8 transfer to E2,
reversion to an alternate E1 conformation would facilitate release of
the covalent E2-NEDD8 thioester product. Thus, Huang et al. (2007)
concluded that transferring the UBL's thioester linkage between
successive conjugation enzymes can induce conformational changes and
alter interaction networks to drive consecutive steps in UBL cascades.
*FIELD* RF
1. Bohnsack, R. N.; Haas, A. L.: Conservation in the mechanism of
Nedd8 activation by the human AppBp1-Uba3 heterodimer. J. Biol. Chem. 278:
26823-26830, 2003.
2. Fan, M.; Long, X.; Bailey, J. A.; Reed, C. A.; Osborne, E.; Gize,
E. A.; Kirk, E. A.; Bigsby, R. M.; Nephew, K. P.: The activating
enzyme of NEDD8 inhibits steroid receptor function. Molec. Endocr. 16:
315-330, 2002.
3. Huang, D. T.; Hung, H. W.; Zhuang, M.; Ohi, M. D.; Holton, J. M.;
Schulman, B. A.: Basis for a ubiquitin-like protein thioester switch
toggling E1-E2 affinity. Nature 445: 394-398, 2007.
4. Osaka, F.; Kawasaki, H.; Aida, N.; Saeki, M.; Chiba, T.; Kawashima,
S.; Tanaka, K.; Kato, S.: A new NEDD8-ligating system for cullin-4A. Genes
Dev. 12: 2263-2268, 1998.
5. Soucy, T. A.; Smith, P. G.; Milhollen, M. A.; Berger, A. J.; Gavin,
J. M.; Adhikari, S.; Brownell, J. E.; Burke, K. E.; Cardin, D. P.;
Critchley, S.; Cullis, C. A.; Doucette, A.; and 23 others: An inhibitor
of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458:
732-736, 2009.
6. Walden, H.; Podgorski, M. S.; Schulman, B. A.: Insights into the
ubiquitin transfer cascade from the structure of the activating enzyme
for NEDD8. Nature 422: 330-334, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 8/28/2009
Ada Hamosh - updated: 4/28/2009
Ada Hamosh - updated: 2/23/2007
Ada Hamosh - updated: 4/1/2003
John A. Phillips, III - updated: 7/11/2002
*FIELD* CD
Rebekah S. Rasooly: 10/21/1998
*FIELD* ED
mgross: 09/08/2009
mgross: 9/8/2009
terry: 8/28/2009
alopez: 5/5/2009
terry: 4/28/2009
wwang: 12/17/2008
alopez: 3/2/2007
terry: 2/23/2007
terry: 2/3/2006
carol: 5/12/2004
alopez: 4/1/2003
terry: 4/1/2003
alopez: 7/11/2002
alopez: 3/4/1999
psherman: 10/21/1998
*RECORD*
*FIELD* NO
603172
*FIELD* TI
*603172 UBIQUITIN-ACTIVATING ENZYME E1C; UBE1C
;;UBIQUITIN-ACTIVATING ENZYME 3, S. CEREVISIAE, HOMOLOG OF; UBA3
read more*FIELD* TX
CLONING
Ubiquitin (191339) is covalently attached to target proteins by a
multienzymatic system consisting of E1 (ubiquitin-activating), E2
(ubiquitin-conjugating), and E3 (ubiquitin-ligating) enzymes. Osaka et
al. (1998) found that NEDD8 (603171), a ubiquitin-like protein, is
conjugated to proteins in a manner analogous to ubiquitylation. They
found that beta-amyloid precursor protein-binding protein-1 (APPBP1;
603385) can bind to NEDD8 in rabbit reticulocyte lysates. However, since
APPBP1 shows similarity to only the N-terminal domain of an E1 enzyme,
the authors reasoned that it must interact with a protein showing
similarity to the C-terminal region of E1s. By searching sequence
databases, Osaka et al. (1998) identified cDNAs encoding UBA3, the human
homolog of yeast Uba3. The predicted 442-amino acid UBA3 protein shares
43% sequence identity with yeast Uba3. In vitro, UBA3 formed a complex
with APPBP1 and a thioester linkage with NEDD8. Osaka et al. (1998)
suggested that the APPBP1/UBA3 complex functions as an E1-like enzyme
for the activation of NEDD8.
To identify novel steroid receptor-interacting proteins, Fan et al.
(2002) performed yeast 2-hybrid screening of a rat uterine luminal
epithelium cDNA library using the ligand-binding and hinge region of
ER-alpha (133430) as bait. They cloned and characterized a cDNA encoding
a protein homologous to yeast and human UBA3, the catalytic subunit of
the activating enzyme of the ubiquitin-like NEDD8 conjugation pathway
(known as neddylation). Sequence analysis revealed that Uba3 contains
multiple nuclear receptor (NR)-interacting motifs (NR boxes), which are
known to mediate interactions between coregulatory proteins and
ligand-activated NRs. Yeast 2-hybrid and glutathione-S-transferase
pull-down assays demonstrated that Uba3 directly interacts with
ligand-occupied ER-alpha and ER-beta (601663). Transient transfection of
Uba3 in mammalian cells inhibited ER-mediated transactivation in a
time-dependent fashion. The authors concluded that UBA3 inhibits
transcription induced by steroid hormone receptors through a novel
mechanism that involves the neddylation pathway.
GENE FUNCTION
The NEDD8-activating enzyme, or NAE, composed of NAE1 (603385) and UBA3
subunits, is an essential component of the NEDD8 contribution pathway
that controls the activity of the cullin-RING subtype of ubiquitin
ligases, thereby regulating the turnover of a subset of proteins
upstream of the proteasome. Substrates of cullin-RING ligases have
important roles in cellular processes associated with cancer cell growth
and survival pathways. Soucy et al. (2009) described MLN4924, a potent
and selective inhibitor of NAE. MLN4924 disrupts cullin-RING
ligase-mediated protein turnover leading to apoptotic death in human
tumor cells by a new mechanism of action, the deregulation of S-phase
DNA synthesis. MLN4924 suppressed the growth of human tumor xenografts
in mice at compound exposures that were well tolerated. Soucy et al.
(2009) concluded that NAE inhibitors may hold promise for the treatment
of cancer.
BIOCHEMICAL FEATURES
Walden et al. (2003) reported the structure and mutational analysis of
human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8. Each E1
activity is specified by a domain: an adenylation domain resembling
bacterial adenylating enzymes, an E1-specific domain organized around
the catalytic cysteine, and a domain involved in E2 recognition
resembling ubiquitin. The domains are arranged around 2 clefts that
coordinate protein and nucleotide binding so that each of E1's reactions
drives the next, in an assembly-line fashion.
Bohnsack and Haas (2003) purified APPBP1-UBA3 from human erythrocytes
and analyzed the kinetics of NEDD8 activation. In the presence of
radiolabeled ATP and radiolabeled recombinant NEDD8, APPBP1-UBA3 rapidly
formed a stable stoichiometric ternary complex composed of tightly bound
NEDD8 adenylate and UBA3-NEDD8 thiol ester. Isotope exchange kinetics
showed that the heterodimer followed a pseudo-ordered mechanism with ATP
the leading and NEDD8 the trailing substrate. Ala72 of NEDD8 was
critical in binding APPBP1-UBA3. Bohnsack and Haas (2003) concluded that
the mechanism of NEDD8 activation by APPBP1-UBA3 shows a high degree of
conservation with ubiquitin activation by UBA1.
Huang et al. (2007) reported the structural analysis of a trapped
ubiquitin-like protein (UBL) activation complex for the human NEDD8
pathway containing NEDD8's heterodimeric E1 (APPBP1-UBA3), 2 NEDD8s (1
thioester-linked to E1, 1 noncovalently associated for adenylation), a
catalytically inactive E2 (UBC12; 603173), and MgATP. The results
suggested that a thioester switch toggles E1-E2 affinities. Two E2
binding sites depend on NEDD8 being thioester-linked to E1. One is
unmasked by a striking E1 conformational change. The other comes
directly from the thioester-bound NEDD8. After NEDD8 transfer to E2,
reversion to an alternate E1 conformation would facilitate release of
the covalent E2-NEDD8 thioester product. Thus, Huang et al. (2007)
concluded that transferring the UBL's thioester linkage between
successive conjugation enzymes can induce conformational changes and
alter interaction networks to drive consecutive steps in UBL cascades.
*FIELD* RF
1. Bohnsack, R. N.; Haas, A. L.: Conservation in the mechanism of
Nedd8 activation by the human AppBp1-Uba3 heterodimer. J. Biol. Chem. 278:
26823-26830, 2003.
2. Fan, M.; Long, X.; Bailey, J. A.; Reed, C. A.; Osborne, E.; Gize,
E. A.; Kirk, E. A.; Bigsby, R. M.; Nephew, K. P.: The activating
enzyme of NEDD8 inhibits steroid receptor function. Molec. Endocr. 16:
315-330, 2002.
3. Huang, D. T.; Hung, H. W.; Zhuang, M.; Ohi, M. D.; Holton, J. M.;
Schulman, B. A.: Basis for a ubiquitin-like protein thioester switch
toggling E1-E2 affinity. Nature 445: 394-398, 2007.
4. Osaka, F.; Kawasaki, H.; Aida, N.; Saeki, M.; Chiba, T.; Kawashima,
S.; Tanaka, K.; Kato, S.: A new NEDD8-ligating system for cullin-4A. Genes
Dev. 12: 2263-2268, 1998.
5. Soucy, T. A.; Smith, P. G.; Milhollen, M. A.; Berger, A. J.; Gavin,
J. M.; Adhikari, S.; Brownell, J. E.; Burke, K. E.; Cardin, D. P.;
Critchley, S.; Cullis, C. A.; Doucette, A.; and 23 others: An inhibitor
of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458:
732-736, 2009.
6. Walden, H.; Podgorski, M. S.; Schulman, B. A.: Insights into the
ubiquitin transfer cascade from the structure of the activating enzyme
for NEDD8. Nature 422: 330-334, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 8/28/2009
Ada Hamosh - updated: 4/28/2009
Ada Hamosh - updated: 2/23/2007
Ada Hamosh - updated: 4/1/2003
John A. Phillips, III - updated: 7/11/2002
*FIELD* CD
Rebekah S. Rasooly: 10/21/1998
*FIELD* ED
mgross: 09/08/2009
mgross: 9/8/2009
terry: 8/28/2009
alopez: 5/5/2009
terry: 4/28/2009
wwang: 12/17/2008
alopez: 3/2/2007
terry: 2/23/2007
terry: 2/3/2006
carol: 5/12/2004
alopez: 4/1/2003
terry: 4/1/2003
alopez: 7/11/2002
alopez: 3/4/1999
psherman: 10/21/1998