CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-015978
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
417EALLKVIKFLGDEQDubiquitination[1]
674MRHQPTLKTDATTAIubiquitination[2]
1107STASALTKLLTKGLSubiquitination[2]
1111ALTKLLTKGLSWQPPubiquitination[2]
1470DLIMTAIKRNGADYRubiquitination[2]
1608KRRAQMTKYLQSNSNubiquitination[2]
1718DIKRKENKGNDTPLAubiquitination[2]
1733LESTNTEKETSLEETubiquitination[2]
1917EFENLRIKGPNAVQLubiquitination[2]
1926PNAVQLVKTTPLKPSubiquitination[2]
1931LVKTTPLKPSPLPVIubiquitination[2]
2219IIRLFLKKGLVNDLAubiquitination[2]
2248NTVNAALKPLETLSRubiquitination[2]
2267PSSLFGSKSASSKNKubiquitination[2]
3228ELCIETPKLTTSEEKubiquitination[1]
3329DTLIQLAKVFPSHFTubiquitination[2]
3393RKGKNSVKSVPVSAGubiquitination[2]
3436RSSLLTEKLLRLLSLubiquitination[2]
3542KGSKSPAKVSDGGSSubiquitination[2]
3659EEQPQTTKLKGKMQSubiquitination[1]
3681VVIVASQKRPLGGREubiquitination[1, 2]
3819DGTPQGEKEKEERPPubiquitination[2]
3896ESQLAHIKDEPPPLSubiquitination[2]
Reference
 [1] 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]
 [2] 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
 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 NPGVTEVLAQ QRAEQQRREL AQNASSDTPM DPVTFIQTLP SDLRRSVLED 3060
MEDSVLAVMP PDIAAEAQAL RREQEARQRQ LMHERLFGHS STSALSAILR SPAFTSRLSG 3120
NRGVQYTRLA VQRGGTFQMG GSSSHNRPSG SNVDTLLRLR GRLLLDHEAL SCLLVLLFVD 3180
EPKLNTSRLH RVLRNLCYHA QTRHWVIRSL LSILQRSSES ELCIETPKLT TSEEKGKKSS 3240
KSCGSSSHEN RPLDLLHKME SKSSNQLSWL SVSMDAALGC RTNIFQIQRS GGRKHTEKHA 3300
SGGSTVHIHP QAAPVVCRHV LDTLIQLAKV FPSHFTQQRT KETNCESDRE RGNKACSPCS 3360
SQSSSSGICT DFWDLLVKLD NMNVSRKGKN SVKSVPVSAG GEGETSPYSL EASPLGQLMN 3420
MLSHPVIRRS SLLTEKLLRL LSLISIALPE NKVSEAQANS GSGASSTTTA TSTTSTTTTT 3480
AASTTPTPPT APTPVTSAPA LVAATAISTI VVAASTTVTT PTTATTTVSI SPTTKGSKSP 3540
AKVSDGGSSS TDFKMVSSGL TENQLQLSVE VLTSHSCSEE GLEDAANVLL QLSRGDSGTR 3600
DTVLKLLLNG ARHLGYTLCK QIGTLLAELR EYNLEQQRRA QCETLSPDGL PEEQPQTTKL 3660
KGKMQSRFDM AENVVIVASQ KRPLGGRELQ LPSMSMLTSK TSTQKFFLRV LQVIIQLRDD 3720
TRRANKKAKQ TGRLGSSGLG SASSIQAAVR QLEAEADAII QMVREGQRAR RQQQAATSES 3780
SQSEASVRRE ESPMDVDQPS PSAQDTQSIA SDGTPQGEKE KEERPPELPL LSEQLSLDEL 3840
WDMLGECLKE LEESHDQHAV LVLQPAVEAF FLVHATERES KPPVRDTRES QLAHIKDEPP 3900
PLSPAPLTPA TPSSLDPFFS REPSSMHISS SLPPDTQKFL RFAETHRTVL NQILRQSTTH 3960
LADGPFAVLV DYIRVLDFDV KRKYFRQELE RLDEGLRKED MAVHVRRDHV FEDSYRELHR 4020
KSPEEMKNRL YIVFEGEEGQ DAGGLLREWY MIISREMFNP MYALFRTSPG DRVTYTINPS 4080
SHCNPNHLSY FKFVGRIVAK AVYDNRLLEC YFTRSFYKHI LGKSVRYTDM ESEDYHFYQG 4140
LVYLLENDVS TLGYDLTFST EVQEFGVCEV RDLKPNGANI LVTEENKKEY VHLVCQMRMT 4200
GAIRKQLAAF LEGFYEIIPK RLISIFTEQE LELLISGLPT IDIDDLKSNT EYHKYQSNSI 4260
QIQWFWRALR SFDQADRAKF LQFVTGTSKV PLQGFAALEG MNGIQKFQIH RDDRSTDRLP 4320
SAHTCFNQLD LPAYESFEKL RHMLLLAIQE CSEGFGLA 4358 
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