CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-015977
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase HUWE1 
Protein Synonyms/Alias
 ARF-binding protein 1; ARF-BP1; HECT, UBA and WWE domain-containing protein 1; Homologous to E6AP carboxyl terminus homologous protein 9; HectH9; Large structure of UREB1; LASU1; Mcl-1 ubiquitin ligase E3; Mule; Upstream regulatory element-binding protein 1; URE-B1; URE-binding protein 1 
Gene Name
 HUWE1 
Gene Synonyms/Alias
 KIAA0312; KIAA1578; UREB1; HSPC272 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
173LAESWGGKENGFGLAubiquitination[1]
190CRDLHMMKYPPSATTubiquitination[1, 2]
245EIMESLTKMYSIPKDubiquitination[2]
324DKQLMEIKAASLRTLubiquitination[3, 4]
476KECPFVIKPKIQRPNubiquitination[1]
509PQRAALLKSMLNFLKacetylation[5]
509PQRAALLKSMLNFLKubiquitination[2, 6]
632QPFERLFKVLLSPDYubiquitination[3, 4]
674MRHQPTLKTDATTAIubiquitination[2, 3, 4]
1037SDSKGKSKITPAMAAubiquitination[1]
1050AARIKQIKPLLSASSubiquitination[3, 4]
1107STASALTKLLTKGLSubiquitination[2, 3, 4, 7]
1111ALTKLLTKGLSWQPPubiquitination[2, 3, 4]
1147PMLFDERKYPYHLMLubiquitination[2, 3, 4]
1225SPHSLPAKLPGGVQNubiquitination[2, 3, 4]
1247RFLVVTQKAAFTCIKubiquitination[2]
1254KAAFTCIKNLWNRKPubiquitination[1, 6]
1295RERLSKEKEGSRGEEubiquitination[2]
1470DLIMTAIKRNGADYRubiquitination[7, 8]
1608KRRAQMTKYLQSNSNubiquitination[2, 3, 4, 7]
1643STIDSAWKSGETSVRubiquitination[7]
1693PRLNKNSKNSNGQELubiquitination[2]
1702SNGQELEKTLEESKEubiquitination[2, 3, 4]
1708EKTLEESKEMDIKRKubiquitination[1, 2]
1713ESKEMDIKRKENKGNubiquitination[1]
1718DIKRKENKGNDTPLAubiquitination[2]
1733LESTNTEKETSLEETubiquitination[1, 2]
1799AMMFAELKSTRMILNubiquitination[2]
1840TLRHTMEKVVRSAATacetylation[5]
1840TLRHTMEKVVRSAATubiquitination[2]
1917EFENLRIKGPNAVQLubiquitination[1, 2, 3, 4, 7]
1926PNAVQLVKTTPLKPSubiquitination[2, 3, 4]
1931LVKTTPLKPSPLPVIubiquitination[1, 2, 3, 4]
2218NIIRLFLKKGLVNDLubiquitination[2]
2219IIRLFLKKGLVNDLAubiquitination[2, 7]
2248NTVNAALKPLETLSRacetylation[5]
2248NTVNAALKPLETLSRubiquitination[2, 3, 4]
2267PSSLFGSKSASSKNKubiquitination[1, 2, 3, 4, 6, 7]
2656TRWTEECKVLDAESMubiquitination[1]
2671HDCVSVVKVSIVNHLubiquitination[1]
2695ERREKRRKQLAEEETubiquitination[2]
2703QLAEEETKITDKGKEubiquitination[1, 2]
3244ELCIETPKLTTSEEKubiquitination[1, 2, 7]
3257EKGKKSSKSCGSSSHubiquitination[1]
3274RPLDLLHKMESKSSNubiquitination[1, 7]
3314GGRKHTEKHASGGSTubiquitination[1]
3345DTLIQLAKVFPSHFTubiquitination[2, 3, 6, 7, 8, 9]
3357HFTQQRTKETNCESDubiquitination[6, 7]
3370SDRERGNKACSPCSSubiquitination[1, 7]
3452RSSLLTEKLLRLLSLubiquitination[1, 2, 3, 6, 7, 8]
3558KGSKSPAKVSDGGSSubiquitination[1, 2, 7]
3621GTRDTVLKLLLNGARubiquitination[2, 3]
3636HLGYTLCKQIGTLLAubiquitination[2]
3677QPQTTKLKGKMQSRFubiquitination[7]
3697VVIVASQKRPLGGREubiquitination[2, 3, 7]
3837TPQGEKEKEERPPELubiquitination[2]
3912ESQLAHIKDEPPPLSubiquitination[2, 3]
3954SLPPDTQKFLRFAETubiquitination[3]
3999LDFDVKRKYFRQELEubiquitination[2, 7]
4043RKSPEEMKNRLYIVFubiquitination[2]
4116FVGRIVAKAVYDNRLubiquitination[2, 8]
4190VCEVRDLKPNGANILubiquitination[2]
4295FDQADRAKFLQFVTGubiquitination[2, 3]
4305QFVTGTSKVPLQGFAubiquitination[3]
4322EGMNGIQKFQIHRDDubiquitination[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] 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]
 [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] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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] 
Functional Description
 E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. 
Sequence Annotation
 DOMAIN 1316 1355 UBA.
 REPEAT 1370 1389 UIM.
 DOMAIN 1603 1680 WWE.
 DOMAIN 4038 4374 HECT.
 ACT_SITE 4341 4341 Glycyl thioester intermediate.
 MOD_RES 1084 1084 Phosphoserine.
 MOD_RES 1368 1368 Phosphoserine.
 MOD_RES 1370 1370 Phosphoserine.
 MOD_RES 1395 1395 Phosphoserine.
 MOD_RES 1722 1722 Phosphothreonine.
 MOD_RES 1907 1907 Phosphoserine.
 MOD_RES 2362 2362 Phosphoserine.
 MOD_RES 2365 2365 Phosphoserine.
 MOD_RES 2391 2391 Phosphoserine.
 MOD_RES 2595 2595 Phosphoserine.
 MOD_RES 2619 2619 Phosphoserine.
 MOD_RES 2751 2751 Phosphothreonine.
 MOD_RES 2887 2887 Phosphoserine.
 MOD_RES 2918 2918 Phosphoserine.
 MOD_RES 3116 3116 Phosphoserine.
 MOD_RES 3127 3127 Phosphoserine.
 MOD_RES 3662 3662 Phosphoserine.
 MOD_RES 3752 3752 Phosphoserine.
 MOD_RES 3757 3757 Phosphoserine.
 MOD_RES 3760 3760 Phosphoserine.
 MOD_RES 3808 3808 Phosphoserine.
 MOD_RES 3816 3816 Phosphoserine.
 MOD_RES 3919 3919 Phosphoserine.
 MOD_RES 3924 3924 Phosphothreonine.
 MOD_RES 3927 3927 Phosphothreonine.  
Keyword
 3D-structure; Alternative splicing; Chromosomal rearrangement; Complete proteome; Cytoplasm; Differentiation; Disease mutation; DNA damage; DNA repair; DNA-binding; Ligase; Mental retardation; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 4374 AA 
Protein Sequence
MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR 60
FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT 120
TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA 180
ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM 240
ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI 300
LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP 360
VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG 420
DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ 480
RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL 540
KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV 600
LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG 660
SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH 720
AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI 780
LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV 840
LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH 900
AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL 960
PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS MDASTQGLLE GIGLDGDTLA 1020
PMETDEPTAS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR 1080
QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP 1140
MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD 1200
AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF TCIKNLWNRK 1260
PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEDTGQEEGG SRREPQVNQQ 1320
QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA 1380
MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT 1440
DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL 1500
PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL 1560
LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF 1620
DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML 1680
TLLRVPRLNK NSKNSNGQEL EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET 1740
KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS 1800
TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG 1860
SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN 1920
AVQLVKTTPL KPSPLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG VMTQEVGQLL 1980
QDMGDDVYQQ YRSLTRQSSD FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR 2040
DGKKDKEGDR ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE 2100
LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL 2160
GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG 2220
LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ 2280
GASQDSSSNQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ 2340
EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR 2400
EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD 2460
DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV 2520
RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL 2580
LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT 2640
LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE 2700
ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS TDAATSESKE 2760
TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL LMPVEPEELG PTRPSGEAET 2820
TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTSAAGSS 2880
EQPRAGSSTP GDAPPAVAEV QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS 2940
RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS 3000
TNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA SSDTPMDPVT 3060
FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ EARQRQLMHE RLFGHSSTSA 3120
LSAILRSPAF TSRLSGNRGV QYTRLAVQRG GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL 3180
LDHEALSCLL VLLFVDEPKL NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI 3240
ETPKLTTSEE KGKKSSKSCG SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI 3300
FQIQRSGGRK HTEKHASGGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH FTQQRTKETN 3360
CESDRERGNK ACSPCSSQSS SSGICTDFWD LLVKLDNMNV SRKGKNSVKS VPVSAGGEGE 3420
TSPYSLEASP LGQLMNMLSH PVIRRSSLLT EKLLRLLSLI SIALPENKVS EAQANSGSGA 3480
SSTTTATSTT STTTTTAAST TPTPPTAPTP VTSAPALVAA TAISTIVVAA STTVTTPTTA 3540
TTTVSISPTT KGSKSPAKVS DGGSSSTDFK MVSSGLTENQ LQLSVEVLTS HSCSEEGLED 3600
AANVLLQLSR GDSGTRDTVL KLLLNGARHL GYTLCKQIGT LLAELREYNL EQQRRAQCET 3660
LSPDGLPEEQ PQTTKLKGKM QSRFDMAENV VIVASQKRPL GGRELQLPSM SMLTSKTSTQ 3720
KFFLRVLQVI IQLRDDTRRA NKKAKQTGRL GSSGLGSASS IQAAVRQLEA EADAIIQMVR 3780
EGQRARRQQQ AATSESSQSE ASVRREESPM DVDQPSPSAQ DTQSIASDGT PQGEKEKEER 3840
PPELPLLSEQ LSLDELWDML GECLKELEES HDQHAVLVLQ PAVEAFFLVH ATERESKPPV 3900
RDTRESQLAH IKDEPPPLSP APLTPATPSS LDPFFSREPS SMHISSSLPP DTQKFLRFAE 3960
THRTVLNQIL RQSTTHLADG PFAVLVDYIR VLDFDVKRKY FRQELERLDE GLRKEDMAVH 4020
VRRDHVFEDS YRELHRKSPE EMKNRLYIVF EGEEGQDAGG LLREWYMIIS REMFNPMYAL 4080
FRTSPGDRVT YTINPSSHCN PNHLSYFKFV GRIVAKAVYD NRLLECYFTR SFYKHILGKS 4140
VRYTDMESED YHFYQGLVYL LENDVSTLGY DLTFSTEVQE FGVCEVRDLK PNGANILVTE 4200
ENKKEYVHLV CQMRMTGAIR KQLAAFLEGF YEIIPKRLIS IFTEQELELL ISGLPTIDID 4260
DLKSNTEYHK YQSNSIQIQW FWRALRSFDQ ADRAKFLQFV TGTSKVPLQG FAALEGMNGI 4320
QKFQIHRDDR STDRLPSAHT CFNQLDLPAY ESFEKLRHML LLAIQECSEG FGLA 4374 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0003677; F:DNA binding; ISS:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0006284; P:base-excision repair; IMP:UniProtKB.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0016574; P:histone ubiquitination; IDA:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
 GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome. 
Interpro
 IPR016024; ARM-type_fold.
 IPR025527; DUF4414.
 IPR010309; E3_Ub_ligase_DUF908.
 IPR010314; E3_Ub_ligase_DUF913.
 IPR000569; HECT.
 IPR009060; UBA-like.
 IPR000449; UBA/transl_elong_EF1B_N.
 IPR015940; UBA/transl_elong_EF1B_N_euk.
 IPR004170; WWE-dom. 
Pfam
 PF14377; DUF4414
 PF06012; DUF908
 PF06025; DUF913
 PF00632; HECT
 PF00627; UBA
 PF02825; WWE 
SMART
 SM00119; HECTc
 SM00165; UBA 
PROSITE
 PS50237; HECT
 PS50030; UBA
 PS50330; UIM
 PS50918; WWE 
PRINTS