CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-024202
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin-like modifier-activating enzyme 6 
Protein Synonyms/Alias
 Ubiquitin-activating enzyme 6; Monocyte protein 4; MOP-4; Ubiquitin-activating enzyme E1-like protein 2; E1-L2 
Gene Name
 UBA6 
Gene Synonyms/Alias
 MOP4; UBE1L2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
58LGDTAMQKMAKSHVFubiquitination[1]
61TAMQKMAKSHVFLSGubiquitination[1]
169MKLPLQKKINDFCRSubiquitination[1]
182RSQCPPIKFISADVHubiquitination[1]
295AVQVKTPKTVFFESLubiquitination[1, 2, 3]
342FQEKYSRKPNVGCQQubiquitination[1]
490GVGTSKEKGMITVTDubiquitination[1]
503TDPDLIEKSNLNRQFubiquitination[1, 2, 3]
521PHHIQKPKSYTAADAubiquitination[3]
544KIDAHLNKVCPTTETacetylation[4, 5, 6]
544KIDAHLNKVCPTTETubiquitination[1, 3, 6, 7, 8, 9]
628EIPFCTLKSFPAAIEubiquitination[10]
644TIQWARDKFESSFSHubiquitination[3, 7]
652FESSFSHKPSLFNKFubiquitination[3, 7]
672SAEEVLQKIQSGHSLubiquitination[8]
687EGCFQVIKLLSRRPRubiquitination[3, 6, 7, 8]
709LARLKFEKYFNHKALubiquitination[3]
714FEKYFNHKALQLLHCubiquitination[8]
729FPLDIRLKDGSLFWQubiquitination[1, 3, 6, 7]
739SLFWQSPKRPPSPIKubiquitination[2, 3, 7, 10, 11]
746KRPPSPIKFDLNEPLubiquitination[3]
796EVKIQEFKPSNKVVQubiquitination[3]
800QEFKPSNKVVQTDETubiquitination[3, 7]
810QTDETARKPDHVPISubiquitination[1]
830NAIFQLEKAILSNEAubiquitination[1, 2, 3, 7]
871AASNLRAKMYSIEPAubiquitination[1, 3]
882IEPADRFKTKRIAGKubiquitination[3, 7]
889KTKRIAGKIIPAIATubiquitination[3, 7, 11]
1003PVMPGHAKRLKLTMHubiquitination[3]
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] 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]
 [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] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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]
 [11] 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] 
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. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. 
Sequence Annotation
 NP_BIND 470 500 ATP (By similarity).
 ACT_SITE 625 625 Glycyl thioester intermediate (By
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 544 544 N6-acetyllysine.  
Keyword
 Acetylation; Alternative splicing; ATP-binding; Complete proteome; Ligase; Nucleotide-binding; Polymorphism; Reference proteome; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1052 AA 
Protein Sequence
MEGSEPVAAH QGEEASCSSW GTGSTNKNLP IMSTASVEID DALYSRQRYV LGDTAMQKMA 60
KSHVFLSGMG GLGLEIAKNL VLAGIKAVTI HDTEKCQAWD LGTNFFLSED DVVNKRNRAE 120
AVLKHIAELN PYVHVTSSSV PFNETTDLSF LDKYQCVVLT EMKLPLQKKI NDFCRSQCPP 180
IKFISADVHG IWSRLFCDFG DEFEVLDTTG EEPKEIFISN ITQANPGIVT CLENHPHKLE 240
TGQFLTFREI NGMTGLNGSI QQITVISPFS FSIGDTTELE PYLHGGIAVQ VKTPKTVFFE 300
SLERQLKHPK CLIVDFSNPE APLEIHTAML ALDQFQEKYS RKPNVGCQQD SEELLKLATS 360
ISETLEEKPD VNADIVHWLS WTAQGFLSPL AAAVGGVASQ EVLKAVTGKF SPLCQWLYLE 420
AADIVESLGK PECEEFLPRG DRYDALRACI GDTLCQKLQN LNIFLVGCGA IGCEMLKNFA 480
LLGVGTSKEK GMITVTDPDL IEKSNLNRQF LFRPHHIQKP KSYTAADATL KINSQIKIDA 540
HLNKVCPTTE TIYNDEFYTK QDVIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT 600
EVIVPHLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS HKPSLFNKFW 660
QTYSSAEEVL QKIQSGHSLE GCFQVIKLLS RRPRNWSQCV ELARLKFEKY FNHKALQLLH 720
CFPLDIRLKD GSLFWQSPKR PPSPIKFDLN EPLHLSFLQN AAKLYATVYC IPFAEEDLSA 780
DALLNILSEV KIQEFKPSNK VVQTDETARK PDHVPISSED ERNAIFQLEK AILSNEATKS 840
DLQMAVLSFE KDDDHNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATTTAT 900
VSGLVALEMI KVTGGYPFEA YKNCFLNLAI PIVVFTETTE VRKTKIRNGI SFTIWDRWTV 960
HGKEDFTLLD FINAVKEKYG IEPTMVVQGV KMLYVPVMPG HAKRLKLTMH KLVKPTTEKK 1020
YVDLTVSFAP DIDGDEDLPG PPVRYYFSHD TD 1052 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:LIFEdb.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019780; F:FAT10 activating enzyme activity; IMP:UniProtKB.
 GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
 GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. 
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.
 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.