CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005074
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin-like modifier-activating enzyme 1 
Protein Synonyms/Alias
 Protein A1S9; Ubiquitin-activating enzyme E1 
Gene Name
 UBA1 
Gene Synonyms/Alias
 A1S9T; UBE1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
9SSSPLSKKRRVSGPDubiquitination[1]
68VLGHEAMKRLQTSSVubiquitination[1, 2, 3, 4]
89GLGVEIAKNIILGGVubiquitination[1, 2, 3, 4, 5, 6, 7, 8]
185FCHNRGIKLVVADTRubiquitination[1, 2, 3, 4, 5, 7, 8]
296GGIVSQVKVPKKISFubiquitination[1, 3, 8]
300SQVKVPKKISFKSLVubiquitination[1]
304VPKKISFKSLVASLAubiquitination[2, 4]
322FVVTDFAKFSRPAQLubiquitination[1, 2, 3, 4, 8]
385LDEDLIRKLAYVAAGubiquitination[1]
443KEVLTEDKCLQRQNRubiquitination[2, 3, 4, 8]
465FGSDLQEKLGKQKYFacetylation[9]
465FGSDLQEKLGKQKYFubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 10, 11]
470QEKLGKQKYFLVGAGubiquitination[1, 2, 3, 4, 6, 8, 11]
510TDMDTIEKSNLNRQFubiquitination[6]
526FRPWDVTKLKSDTAAubiquitination[2, 3, 4, 6]
528PWDVTKLKSDTAAAAubiquitination[1, 5, 6, 7, 8, 10, 11]
593RRCVYYRKPLLESGTubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12]
604ESGTLGTKGNVQVVIubiquitination[1, 5, 6, 7, 8, 11]
627SSQDPPEKSIPICTLubiquitination[1, 2, 4, 6, 7, 8, 11, 13]
635SIPICTLKNFPNAIEubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 13, 14]
657DEFEGLFKQPAENVNubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 11]
671NQYLTDPKFVERTLRacetylation[8, 9, 15, 16]
671NQYLTDPKFVERTLRubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 10]
746APFWSGPKRCPHPLTubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 13]
802QVPEFTPKSGVKIHVubiquitination[2, 4, 5, 6, 7, 10]
806FTPKSGVKIHVSDQEubiquitination[1, 7]
838ATLPSPDKLPGFKMYacetylation[8, 9]
838ATLPSPDKLPGFKMYubiquitination[1, 2, 3, 4, 5, 8]
843PDKLPGFKMYPIDFEubiquitination[2, 3, 4]
882IPSADRHKSKLIAGKubiquitination[7]
884SADRHKSKLIAGKIIubiquitination[1]
980KQFLDYFKTEHKLEIacetylation[15]
980KQFLDYFKTEHKLEIubiquitination[2, 4]
1006SFFMPAAKLKERLDQubiquitination[7]
1008FMPAAKLKERLDQPMubiquitination[7]
Reference
 [1] 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]
 [2] 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]
 [3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] 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]
 [5] 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]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [11] 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]
 [12] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [13] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [14] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [15] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [16] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773] 
Functional Description
 Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin- E1 thioester and free AMP. 
Sequence Annotation
 REPEAT 63 199 1-1.
 REPEAT 459 611 1-2.
 NP_BIND 478 507 ATP (By similarity).
 REGION 63 611 2 approximate repeats.
 ACT_SITE 632 632 Glycyl thioester intermediate (By
 MOD_RES 13 13 Phosphoserine.
 MOD_RES 21 21 Phosphoserine (By similarity).
 MOD_RES 24 24 Phosphoserine (By similarity).
 MOD_RES 31 31 Phosphoserine (By similarity).
 MOD_RES 46 46 Phosphoserine.
 MOD_RES 55 55 Phosphotyrosine (By similarity).
 MOD_RES 671 671 N6-acetyllysine.
 MOD_RES 800 800 Phosphothreonine.
 MOD_RES 810 810 Phosphoserine.
 MOD_RES 816 816 Phosphoserine (By similarity).
 MOD_RES 820 820 Phosphoserine (By similarity).
 MOD_RES 835 835 Phosphoserine.
 MOD_RES 980 980 N6-acetyllysine.  
Keyword
 Acetylation; ATP-binding; Complete proteome; Direct protein sequencing; Disease mutation; Ligase; Neurodegeneration; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1058 AA 
Protein Sequence
MSSSPLSKKR RVSGPDPKPG SNCSPAQSVL SEVPSVPTNG MAKNGSEADI DEGLYSRQLY 60
VLGHEAMKRL QTSSVLVSGL RGLGVEIAKN IILGGVKAVT LHDQGTAQWA DLSSQFYLRE 120
EDIGKNRAEV SQPRLAELNS YVPVTAYTGP LVEDFLSGFQ VVVLTNTPLE DQLRVGEFCH 180
NRGIKLVVAD TRGLFGQLFC DFGEEMILTD SNGEQPLSAM VSMVTKDNPG VVTCLDEARH 240
GFESGDFVSF SEVQGMVELN GNQPMEIKVL GPYTFSICDT SNFSDYIRGG IVSQVKVPKK 300
ISFKSLVASL AEPDFVVTDF AKFSRPAQLH IGFQALHQFC AQHGRPPRPR NEEDAAELVA 360
LAQAVNARAL PAVQQNNLDE DLIRKLAYVA AGDLAPINAF IGGLAAQEVM KACSGKFMPI 420
MQWLYFDALE CLPEDKEVLT EDKCLQRQNR YDGQVAVFGS DLQEKLGKQK YFLVGAGAIG 480
CELLKNFAMI GLGCGEGGEI IVTDMDTIEK SNLNRQFLFR PWDVTKLKSD TAAAAVRQMN 540
PHIRVTSHQN RVGPDTERIY DDDFFQNLDG VANALDNVDA RMYMDRRCVY YRKPLLESGT 600
LGTKGNVQVV IPFLTESYSS SQDPPEKSIP ICTLKNFPNA IEHTLQWARD EFEGLFKQPA 660
ENVNQYLTDP KFVERTLRLA GTQPLEVLEA VQRSLVLQRP QTWADCVTWA CHHWHTQYSN 720
NIRQLLHNFP PDQLTSSGAP FWSGPKRCPH PLTFDVNNPL HLDYVMAAAN LFAQTYGLTG 780
SQDRAAVATF LQSVQVPEFT PKSGVKIHVS DQELQSANAS VDDSRLEELK ATLPSPDKLP 840
GFKMYPIDFE KDDDSNFHMD FIVAASNLRA ENYDIPSADR HKSKLIAGKI IPAIATTTAA 900
VVGLVCLELY KVVQGHRQLD SYKNGFLNLA LPFFGFSEPL AAPRHQYYNQ EWTLWDRFEV 960
QGLQPNGEEM TLKQFLDYFK TEHKLEITML SQGVSMLYSF FMPAAKLKER LDQPMTEIVS 1020
RVSKRKLGRH VRALVLELCC NDESGEDVEV PYVRYTIR 1058 
Gene Ontology
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
 GO:0008641; F:small protein activating enzyme activity; IEA:InterPro.
 GO:0008219; P:cell death; IEA:UniProtKB-KW.
 GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. 
Interpro
 IPR009036; Molybdenum_cofac_synth_MoeB.
 IPR016040; NAD(P)-bd_dom.
 IPR000594; ThiF_NAD_FAD-bd.
 IPR018965; Ub-activating_enz_e1_C.
 IPR023280; Ub-like_act_enz_cat_cys_dom.
 IPR000127; UBact_repeat.
 IPR019572; Ubiquitin-activating_enzyme.
 IPR018075; UBQ-activ_enz_E1.
 IPR018074; UBQ-activ_enz_E1_AS.
 IPR000011; UBQ/SUMO-activ_enz_E1-like. 
Pfam
 PF00899; ThiF
 PF09358; UBA_e1_C
 PF10585; UBA_e1_thiolCys
 PF02134; UBACT 
SMART
 SM00985; UBA_e1_C 
PROSITE
 PS00536; UBIQUITIN_ACTIVAT_1
 PS00865; UBIQUITIN_ACTIVAT_2 
PRINTS
 PR01849; UBIQUITINACT.