CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-017952
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 NEDD8-activating enzyme E1 catalytic subunit 
Protein Synonyms/Alias
 NEDD8-activating enzyme E1C; Ubiquitin-activating enzyme E1C; Ubiquitin-like modifier-activating enzyme 3; Ubiquitin-activating enzyme 3 
Gene Name
 UBA3 
Gene Synonyms/Alias
 UBE1C 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
9ADGEEPEKKRRRIEEmethylation[1]
10DGEEPEKKRRRIEELmethylation[1]
21IEELLAEKMAVDGGCubiquitination[2]
86GLGCELLKNLALSGFubiquitination[3]
124PKDIGRPKAEVAAEFubiquitination[2]
147NVVPHFNKIQDFNDTubiquitination[2, 3, 4, 5]
260VRMLQWPKEQPFGEGubiquitination[3]
284HIQWIFQKSLERASQubiquitination[2, 3, 4, 5, 6]
307RLTQGVVKRIIPAVAubiquitination[2, 3, 4, 5]
361YTFEAERKENCPACSubiquitination[2, 3, 4, 5]
398NSASLQMKSPAITATubiquitination[3]
409ITATLEGKNRTLYLQubiquitination[2, 3]
431RTRPNLSKTLKELGLubiquitination[2]
434PNLSKTLKELGLVDGubiquitination[2, 3]
Reference
 [1] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression. 
Sequence Annotation
 NP_BIND 100 124 ATP.
 NP_BIND 148 171 ATP.
 REGION 53 70 Interaction with UBE2M N-terminus.
 REGION 157 161 Interaction with UBE2M N-terminus.
 REGION 192 217 Interaction with UBE2M N-terminus.
 REGION 227 229 Interaction with NEDD8.
 REGION 242 248 Interaction with NAE1.
 REGION 292 295 Interaction with NAE1.
 REGION 331 338 Interaction with UBE2M N-terminus.
 REGION 352 357 Interaction with NEDD8.
 REGION 368 463 Interaction with UBE2M core domain.
 ACT_SITE 237 237 Glycyl thioester intermediate.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Complete proteome; Ligase; Nucleotide-binding; Polymorphism; Reference proteome; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 463 AA 
Protein Sequence
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST 60
ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDI 120
GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI 180
SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA 240
SMPRLPEHCI EYVRMLQWPK EQPFGEGVPL DGDDPEHIQW IFQKSLERAS QYNIRGVTYR 300
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER 360
KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS 420
IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FTS 463 
Gene Ontology
 GO:0005634; C:nucleus; IDA:LIFEdb.
 GO:0016881; F:acid-amino acid ligase activity; IEA:InterPro.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019781; F:NEDD8 activating enzyme activity; IEA:Compara.
 GO:0006464; P:cellular protein modification process; TAS:ProtInc.
 GO:0007113; P:endomitotic cell cycle; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0045116; P:protein neddylation; IEA:UniProtKB-UniPathway.
 GO:0006508; P:proteolysis; TAS:ProtInc.
 GO:0051726; P:regulation of cell cycle; IEA:Compara. 
Interpro
 IPR014929; E2_binding.
 IPR009036; Molybdenum_cofac_synth_MoeB.
 IPR016040; NAD(P)-bd_dom.
 IPR000594; ThiF_NAD_FAD-bd.
 IPR023318; Ub_act_enz_dom_a.
 IPR000127; UBact_repeat.
 IPR019572; Ubiquitin-activating_enzyme.
 IPR018074; UBQ-activ_enz_E1_AS. 
Pfam
 PF08825; E2_bind
 PF00899; ThiF
 PF10585; UBA_e1_thiolCys
 PF02134; UBACT 
SMART
  
PROSITE
 PS00536; UBIQUITIN_ACTIVAT_1
 PS00865; UBIQUITIN_ACTIVAT_2 
PRINTS