UBA3_HUMAN
ID UBA3_HUMAN Reviewed; 463 AA.
AC Q8TBC4; A6NLB5; A8K027; O76088; Q9NTU3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=NEDD8-activating enzyme E1 catalytic subunit;
DE EC=6.2.1.64 {ECO:0000269|PubMed:9694792};
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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 [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., 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 [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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., 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., 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 [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 project:
RT 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, FUNCTION,
RP 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, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9694792; DOI=10.1101/gad.12.15.2263;
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 AppBp1-Uba3
RT 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., 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 [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 33-463 IN COMPLEX WITH NAE1; NEDD8
RP 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 for
RT 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, AND
RP MUTAGENESIS OF ILE-148; ASP-167; 227-LEU-TYR-228; THR-238; ILE-310 AND
RP 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 the
RT 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 AND
RP UBE2M, AND MUTAGENESIS OF PHE-65; 160-HIS-ILE-161; PRO-192; ILE-195;
RP 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., 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).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 368-463 IN COMPLEX WITH UBE2M, AND
RP MUTAGENESIS OF SER-368; GLN-369; LEU-370; THR-412; LEU-415; VAL-418;
RP 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., 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 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., Scott D.C.,
RA Borg L.A., Neale G., Murray P.J., Roussel M.F., 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 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. Down-
CC regulates steroid receptor activity. Necessary for cell cycle
CC progression. {ECO:0000269|PubMed:10207026, ECO:0000269|PubMed:12740388,
CC ECO:0000269|PubMed:9694792}.
CC -!- CATALYTIC ACTIVITY: [NEDD8-activating enzyme E1 catalytic subunit]:
CC Reaction=ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-
CC cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8
CC protein]-yl-L-cysteine.; EC=6.2.1.64;
CC Evidence={ECO:0000269|PubMed:9694792};
CC -!- ACTIVITY REGULATION: Binding of TP53BP2 to the regulatory subunit NAE1
CC decreases activity.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and
CC UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By similarity).
CC Interacts with TBATA (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q8TBC4; P02649: APOE; NbExp=3; IntAct=EBI-717567, EBI-1222467;
CC Q8TBC4; P05067: APP; NbExp=3; IntAct=EBI-717567, EBI-77613;
CC Q8TBC4; Q96FN4: CPNE2; NbExp=6; IntAct=EBI-717567, EBI-7097057;
CC Q8TBC4; Q9BVJ7: DUSP23; NbExp=3; IntAct=EBI-717567, EBI-724940;
CC Q8TBC4; O14732: IMPA2; NbExp=6; IntAct=EBI-717567, EBI-725233;
CC Q8TBC4; Q13564: NAE1; NbExp=3; IntAct=EBI-717567, EBI-718631;
CC Q8TBC4; P54727: RAD23B; NbExp=2; IntAct=EBI-717567, EBI-954531;
CC Q8TBC4; Q8TBC4: UBA3; NbExp=4; IntAct=EBI-717567, EBI-717567;
CC Q8TBC4; 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 {ECO:0000269|PubMed:10207026}.
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. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC27648.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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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 CCDS; CCDS2909.1; -. [Q8TBC4-1]
DR CCDS; CCDS2910.1; -. [Q8TBC4-2]
DR PIR; T17306; T17306.
DR RefSeq; NP_003959.3; NM_003968.3. [Q8TBC4-1]
DR RefSeq; NP_937838.1; NM_198195.1. [Q8TBC4-2]
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=369-463.
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 PDB; 5JJM; X-ray; 2.15 A; G/H/I/J=62-69.
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 PDBsum; 5JJM; -.
DR AlphaFoldDB; Q8TBC4; -.
DR BMRB; Q8TBC4; -.
DR SMR; Q8TBC4; -.
DR BioGRID; 114503; 76.
DR CORUM; Q8TBC4; -.
DR IntAct; Q8TBC4; 23.
DR MINT; Q8TBC4; -.
DR STRING; 9606.ENSP00000354340; -.
DR BindingDB; Q8TBC4; -.
DR ChEMBL; CHEMBL2016430; -.
DR MoonDB; Q8TBC4; Predicted.
DR GlyGen; Q8TBC4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TBC4; -.
DR MetOSite; Q8TBC4; -.
DR PhosphoSitePlus; Q8TBC4; -.
DR SwissPalm; Q8TBC4; -.
DR BioMuta; UBA3; -.
DR DMDM; 83305811; -.
DR EPD; Q8TBC4; -.
DR jPOST; Q8TBC4; -.
DR MassIVE; Q8TBC4; -.
DR MaxQB; Q8TBC4; -.
DR PaxDb; Q8TBC4; -.
DR PeptideAtlas; Q8TBC4; -.
DR PRIDE; Q8TBC4; -.
DR ProteomicsDB; 73991; -. [Q8TBC4-1]
DR ProteomicsDB; 73992; -. [Q8TBC4-2]
DR Antibodypedia; 31863; 186 antibodies from 29 providers.
DR DNASU; 9039; -.
DR Ensembl; ENST00000349511.8; ENSP00000340041.4; ENSG00000144744.17. [Q8TBC4-2]
DR Ensembl; ENST00000361055.9; ENSP00000354340.4; ENSG00000144744.17. [Q8TBC4-1]
DR GeneID; 9039; -.
DR KEGG; hsa:9039; -.
DR MANE-Select; ENST00000361055.9; ENSP00000354340.4; NM_003968.4; NP_003959.3.
DR UCSC; uc003dno.4; human. [Q8TBC4-1]
DR CTD; 9039; -.
DR DisGeNET; 9039; -.
DR GeneCards; UBA3; -.
DR HGNC; HGNC:12470; UBA3.
DR HPA; ENSG00000144744; Tissue enriched (brain).
DR MIM; 603172; gene.
DR neXtProt; NX_Q8TBC4; -.
DR OpenTargets; ENSG00000144744; -.
DR PharmGKB; PA162407622; -.
DR VEuPathDB; HostDB:ENSG00000144744; -.
DR eggNOG; KOG2015; Eukaryota.
DR GeneTree; ENSGT00550000074831; -.
DR HOGENOM; CLU_013325_13_1_1; -.
DR InParanoid; Q8TBC4; -.
DR OMA; LENYMMY; -.
DR OrthoDB; 686413at2759; -.
DR PhylomeDB; Q8TBC4; -.
DR TreeFam; TF300499; -.
DR BioCyc; MetaCyc:HS07200-MON; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 6.2.1.64; 2681.
DR PathwayCommons; Q8TBC4; -.
DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8TBC4; -.
DR SIGNOR; Q8TBC4; -.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 9039; 571 hits in 1107 CRISPR screens.
DR ChiTaRS; UBA3; human.
DR EvolutionaryTrace; Q8TBC4; -.
DR GeneWiki; UBE1C; -.
DR GenomeRNAi; 9039; -.
DR Pharos; Q8TBC4; Tchem.
DR PRO; PR:Q8TBC4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8TBC4; protein.
DR Bgee; ENSG00000144744; Expressed in palpebral conjunctiva and 209 other tissues.
DR ExpressionAtlas; Q8TBC4; baseline and differential.
DR Genevisible; Q8TBC4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IDA:MGI.
DR GO; GO:0019788; F:NEDD8 transferase activity; TAS:Reactome.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0007113; P:endomitotic cell cycle; IEA:Ensembl.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0045116; P:protein neddylation; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR DisProt; DP02306; -.
DR Gene3D; 1.10.10.520; -; 1.
DR InterPro; IPR014929; E2-binding.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR023318; Ub_act_enz_dom_a_sf.
DR InterPro; IPR030468; Uba3.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR InterPro; IPR033127; UBQ-activ_enz_E1_Cys_AS.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR PANTHER; PTHR10953:SF6; PTHR10953:SF6; 1.
DR Pfam; PF08825; E2_bind; 1.
DR Pfam; PF00899; ThiF; 1.
DR SMART; SM01181; E2_bind; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Ligase; Nucleotide-binding; Reference proteome; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..463
FT /note="NEDD8-activating enzyme E1 catalytic subunit"
FT /id="PRO_0000194941"
FT REGION 53..70
FT /note="Interaction with UBE2M N-terminus"
FT REGION 157..161
FT /note="Interaction with UBE2M N-terminus"
FT REGION 192..217
FT /note="Interaction with UBE2M N-terminus"
FT REGION 227..229
FT /note="Interaction with NEDD8"
FT REGION 242..248
FT /note="Interaction with NAE1"
FT /evidence="ECO:0000269|PubMed:12740388"
FT REGION 292..295
FT /note="Interaction with NAE1"
FT /evidence="ECO:0000269|PubMed:12740388"
FT REGION 331..338
FT /note="Interaction with UBE2M N-terminus"
FT REGION 352..357
FT /note="Interaction with NEDD8"
FT REGION 368..463
FT /note="Interaction with UBE2M core domain"
FT ACT_SITE 237
FT /note="Glycyl thioester intermediate"
FT BINDING 100..124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:14690597"
FT BINDING 148..171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:14690597"
FT SITE 211
FT /note="Determines specificity for NEDD8"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 8..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041127"
FT VARIANT 9
FT /note="K -> R (in dbSNP:rs17852113)"
FT /evidence="ECO:0000269|PubMed:10207026,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_023945"
FT MUTAGEN 65
FT /note="F->G: Reduces affinity for UBE2M."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 148
FT /note="I->A: No effect on NEDD8 adenylation."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 160..161
FT /note="HI->AA: Reduces affinity for UBE2M."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 167
FT /note="D->A: Abolishes NEDD8 adenylation."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 192
FT /note="P->A: Reduces affinity for UBE2M; when associated
FT with A-195 and A-197."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 195
FT /note="I->A: Reduces affinity for UBE2M; when associated
FT with A-192 and A-197."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 197
FT /note="P->A: Reduces affinity for UBE2M; when associated
FT with A-192 and A-195."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 211
FT /note="R->Q: Abolishes specificity for NEDD8."
FT /evidence="ECO:0000269|PubMed:14690597"
FT MUTAGEN 214
FT /note="L->A: Reduces affinity for UBE2M; when associated
FT with A-217."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 217
FT /note="M->A: Reduces affinity for UBE2M; when associated
FT with A-214."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 227..228
FT /note="LY->DD: Strongly reduces NEDD8 adenylation."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 237
FT /note="C->S: Abolishes thioester intermediate formation."
FT /evidence="ECO:0000269|PubMed:10207026"
FT MUTAGEN 238
FT /note="T->A: No effect on NEDD8 adenylation; impairs
FT thioester intermediate formation."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 310
FT /note="I->A: No effect on NEDD8 adenylation or thioester
FT intermediate formation; impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 331
FT /note="I->A: Reduces affinity for UBE2M."
FT /evidence="ECO:0000269|PubMed:15361859"
FT MUTAGEN 352..357
FT /note="YTYTFE->ATATA: Abolishes NEDD8 adenylation."
FT /evidence="ECO:0000269|PubMed:12646924"
FT MUTAGEN 368
FT /note="S->P: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 369
FT /note="Q->P: No effect on NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 370
FT /note="L->P: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 412
FT /note="T->A: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 415
FT /note="L->A: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 418
FT /note="V->A: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 421
FT /note="I->A: Impairs NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT MUTAGEN 424
FT /note="R->A: No effect on NEDD8 transfer to UBE2M."
FT /evidence="ECO:0000269|PubMed:15694336"
FT CONFLICT 146
FT /note="N -> Y (in Ref. 1; CAB55996)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="D -> G (in Ref. 1; CAB55996)"
FT /evidence="ECO:0000305"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:2NVU"
FT TURN 35..38
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 39..46
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 63..67
FT /evidence="ECO:0007829|PDB:5JJM"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 124..135
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:1R4M"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 221..227
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 246..255
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 275..291
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 299..306
FT /evidence="ECO:0007829|PDB:1TT5"
FT HELIX 314..333
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 341..346
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:1TT5"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:1TT5"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:3FN1"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:1R4M"
FT HELIX 382..391
FT /evidence="ECO:0007829|PDB:1Y8X"
FT TURN 393..395
FT /evidence="ECO:0007829|PDB:3FN1"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:1Y8X"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:1Y8X"
FT HELIX 419..430
FT /evidence="ECO:0007829|PDB:1Y8X"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:1Y8X"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:1Y8X"
FT HELIX 437..440
FT /evidence="ECO:0007829|PDB:1R4M"
FT STRAND 443..447
FT /evidence="ECO:0007829|PDB:1Y8X"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:1YOV"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:1Y8X"
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
