Search Results

Overview

Uniprot IDQ7TMY8
Protein NameE3 ubiquitin-protein ligase HUWE1
Gene NameHuwe1
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
1790 LRLTRDHKYAMMFAE

Function

E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15767685, PubMed:18488021). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (By similarity). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (By similarity). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15767685). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (By similarity). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (By similarity). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (By similarity). Mediates polyubiquitination of PA2G4 (By similarity). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquitination and degradation of NR1D1 (By similarity). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (By similarity). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (By similarity). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (By similarity). Ubiquitinates PPARA in hepatocytes (PubMed:29331071)

Protein Sequence

10 MKVDRTKLKK 20 TPTEAPADCR 30 ALIDKLKVCN 40 DEQLLLELQQ 50 IKTWNIGKCE 60 LYHWVDLLDR 70 FDGILADAGQ 80 TVENMSWMLV 90 CDRPEKEQLK 100 MLLLAVLNFT 110 ALLIEYSFSR 120 HLYSSIEHLT 130 TLLASSDMQV 140 VLAVLNLLYV 150 FSKRSNYITR 160 LGSDKRTPLL 170 TRLQHLAESW 180 GGKENGFGLA 190 ECCRDLQMLK 200 YPPSATTLHF 210 EFYADPGAEV 220 KIEKRTTSNT 230 LHYIHIEQLD 240 KISESPSEIM 250 ESLTKMYSIP 260 KDKQMLLFTH 270 IRLAHGFSNH 280 RKRLQAVQAR 290 LHAISILVYS 300 NALQESANSI 310 LYNGLIEELV 320 DVLQITDKQL 330 MEIKAASLRT 340 LTSIVHLERT 350 PKLSSIIDCT 360 GTASYHGFLP 370 VLVRNCIQAM 380 IDPSMDPYPH 390 QFATALFSFL 400 YHLASYDAGG 410 EALVSCGMME 420 ALLKVIKFLG 430 DEQDQITFVT 440 RAVRVVDLIT 450 NLDMAAFQSH 460 SGLSIFIYRL 470 EHEVDLCRKE 480 CPFVIKPKIQ 490 RPSTTQEGEE 500 METDMDGVQC 510 IPQRAALLKS 520 MLNFLKKAIQ 530 DPAFSDGIRH 540 VMDGSLPTSL 550 KHIISNAEYY 560 GPSLFLLATE 570 VVTVFVFQEP 580 SLLSSLQDNG 590 LTDVMLHALL 600 IKDVPATREV 610 LGSLPNVFSA 620 LCLNARGLQS 630 FVQCQPFERL 640 FKVLLSPDYL 650 PAMRRRRSSD 660 PLGDTASNLG 670 SAVDELMRHQ 680 PTLKTDATTA 690 IIKLLEEICN 700 LGRDPKYICQ 710 KPSIQKADGT 720 ATAPPPRSNH 730 AAEEASSEDE 740 EEEEVQAMQS 750 FNSAQQNETE 760 PNQQVVGTEE 770 RIPIPLMDYI 780 LNVMKFVESI 790 LSNNTTDDHC 800 QEFVNQKGLL 810 PLVTILGLPN 820 LPIDFPTSAA 830 CQAVAGVCKS 840 ILTLSHEPKV 850 LQEGLLQLDL 860 ILSSLEPLHR 870 PIESPGGSVL 880 LRELACAGNV 890 ADATLSAQAT 900 PLLHALTAAH 910 AYIMMFVHTC 920 RVGQSEIRSI 930 SVNQWGSQLG 940 LSVLSKLSQL 950 YCSLVWESTV 960 LLSLCTPNSL 970 PSGCEFGQAD 980 MQKLVPKDEK 990 AGTTQGGKRS 1000 DGEQDGTAGS 1010 MDASAQGLLE 1020 GIELDGDTLA 1030 PMETDEPSSS 1040 DSKGKSKITP 1050 AMAARIKQIK 1060 PLLSASSRLG 1070 RALAELFGLL 1080 VKLCVGSPVR 1090 QRRSHHAAST 1100 TTAPTPAARS 1110 TASALTKLLT 1120 KGLSWQPPPY 1130 TPTPRFRLTF 1140 FICSVGFTSP 1150 MLFDERKYPY 1160 HLMLQKFLCS 1170 GGHNALFETF 1180 NWALSMGGKV 1190 PVSEGLEHSD 1200 LPDGTGEFLD 1210 AWLMLVEKMV 1220 NPTTVLESPH 1230 SLPAKLPGGV 1240 QSFPQFSALR 1250 FLVVTQKAAF 1260 TCIKNLWNRK 1270 PLKVYGGRMA 1280 ESMLAILCHI 1290 LRGEPVIRER 1300 LSKEKEGSRG 1310 EEEAGQEEGG 1320 SRREPQVNQQ 1330 QLQQLMDMGF 1340 TREHAMEALL 1350 NTSTMEQATE 1360 YLLTHPPPII 1370 GGVVRDLSMS 1380 EEDQMMRAIA 1390 MSLGQDIPMD 1400 QRAESPEEVA 1410 CRKEEEERKA 1420 REKQEEEEAK 1430 CLEKFQDADP 1440 LEQDELHTFT 1450 DTMLPGCFHL 1460 LDELPDTVYR 1470 VCDLIMTAIK 1480 RNGADYRDMI 1490 LKQVVNQVWE 1500 AADVLIKAAL 1510 PLTTSDTKTV 1520 SEWISQMATL 1530 PQASNLATRI 1540 LLLTLLFEEL 1550 KLPCAWVVES 1560 SGILNVLIKL 1570 LEVVQPCLQA 1580 AKEQKEVQTP 1590 KWITPVLLLI 1600 DFYEKTAISS 1610 KRRAQMTKYL 1620 QSNSNNWRWF 1630 DDRSGRWCSY 1640 SASNNSTIDS 1650 AWKSGETSVR 1660 FTAGRRRYTV 1670 QFTTMVQVNE 1680 ETGNRRPVML 1690 TLLRVPRLSK 1700 NSKSSNGQEL 1710 EKTLEESKET 1720 DIKHKENKGN 1730 DIPLALESTN 1740 TEKEASLDET 1750 KIGEILIQGL 1760 TEDMVTVLIR 1770 ACVSMLGVPV 1780 DPDTLHATLR 1790 LCLRLTRDHK 1800 YAMMFAELKS 1810 TRMILNLTQS 1820 SGFNGFTPLV 1830 TLLLRHIIED 1840 PCTLRHTMEK 1850 VVRSAATSGA 1860 GSTTSGVVSG 1870 SLGSREINYI 1880 LRVLGPAACR 1890 NPDIFTEVAN 1900 CCIRIALPAP 1910 RGSGTASDDE 1920 FENLRIKGPN 1930 AVQLVKTTPL 1940 KPSSLPVIPD 1950 TIKEVIYDML 1960 NALAAYHAPE 1970 EADKSDPKPG 1980 GTTQEVGQLL 1990 QDMGDDVYQQ 2000 YRSLTRQSSD 2010 FDTQSGFSLN 2020 SQVFAADGAP 2030 AETSTTGTSQ 2040 GEASTPEETR 2050 EGKKDKEGDR 2060 TSEEGKQKSK 2070 GSKPLMPTST 2080 ILRLLAELVR 2090 SYVGIATLIA 2100 NYSYTVGQSE 2110 LIKEDCSVLA 2120 FVLDHLLPHT 2130 QNAEDKDTPA 2140 LARLFLASLA 2150 AAGSGTDAQV 2160 ALVNEVKAAL 2170 GRALAMAEST 2180 EKHARLQAVM 2190 CIISTIMESC 2200 PSTSSFYSSA 2210 TAKTQHNGMN 2220 NIIRLFLKKG 2230 LVNDLARVPH 2240 SLDLSSPNMA 2250 NTVNAALKPL 2260 ETLSRIVNQP 2270 SSLFGSKSAS 2280 SKNKSEQDAQ 2290 GASQDSSSHQ 2300 QDPGEPGEAE 2310 VQEEDHDVTQ 2320 TEVADGDIMD 2330 GEAETDSVVI 2340 AGQPEVLSSQ 2350 EMQVENELED 2360 LIDELLERDG 2370 GSGNSTIIVS 2380 RSGEDESQED 2390 VLMDEAPSNL 2400 SQASTLQANR 2410 EDSMNILDPE 2420 DEEEHTQEED 2430 SSGSNEDEDD 2440 SQDEEEEEEE 2450 DEEDDQEDDE 2460 GEEGDEDDDD 2470 DGSEMELDED 2480 YPDMNASPLV 2490 RFERFDREDD 2500 LIIEFDNMFS 2510 SATDIPPSPG 2520 NIPTTHPLMV 2530 RHADHSSLTL 2540 GSGSSTTRLT 2550 QGIGRSQRTL 2560 RQLTANTGHT 2570 IHVHYPGNRQ 2580 PNPPLILQRL 2590 LGPSAAADIL 2600 QLSSSLPLQS 2610 RGRARLLVGN 2620 DDVHIIARSD 2630 DELLDDFFHD 2640 QSTATSQAGT 2650 LSSIPTALTR 2660 WTEECKVLDA 2670 ESMHDCVSVV 2680 KVPIVNHLEF 2690 LRDEELEERR 2700 EKRRKQLAEE 2710 ETKIIDKGKE 2720 DKENRDQSAQ 2730 CTVTKTNDST 2740 EQNVSDGTPM 2750 PDSYPTTPSS 2760 TDAPTSESKE 2770 TLGTLQPSQQ 2780 QPALPPPPSL 2790 GEIPQELQSP 2800 AEEVANSTQL 2810 LMPIELEELG 2820 PTRPSGEAET 2830 TQMELSPAPT 2840 ITSLSPERAE 2850 DSDALTAVSS 2860 QLEGSPMDTS 2870 SLASCTLEEA 2880 VGDTPAAGSS 2890 EQPTAGSSTP 2900 GDAPSVVAEV 2910 QGRPDVSRES 2920 NQPPEDSSPP 2930 ASSESSSTRD 2940 SAVAISGADS 2950 RGILEEPLPS 2960 TSSEEEDPLA 2970 GISLPEGVDP 2980 SFLAALPDDI 2990 RREVLQNQLG 3000 IRPPTRSAPS 3010 SNSSAPAVVG 3020 NPGVTEVSPE 3030 FLAALPPAIQ 3040 EEVLAQQRAE 3050 QQRRELAQNA 3060 SSDTPMDPVT 3070 FIQTLPSDLR 3080 RSVLEDMEDS 3090 VLAVMPPDIA 3100 AEAQALRREQ 3110 EARQRQLMHE 3120 RLFGHSSTSA 3130 LSAILRSPAF 3140 TSRLSGNRGV 3150 QYTRLAVQRG 3160 GTFQMGGSSS 3170 HNRPSGSNVD 3180 TLLRLRGRLL 3190 LDHEALSCLL 3200 VLLFVDEPKL 3210 NTSRLHRVLR 3220 NLCYHAQTRH 3230 WVIRSLLSIL 3240 QRSSESELCI 3250 ETPKLSTSEE 3260 RGKKSSKSCA 3270 SSSHENRPLD 3280 LLHKMESKSS 3290 NQLSWLSVSM 3300 DAALGCRTNI 3310 FQIQRSGGRK 3320 HTEKHASSGS 3330 TVHIHPQAAP 3340 VVCRHVLDTL 3350 IQLAKVFPSH 3360 FTQQRTKETN 3370 CESDRERGSK 3380 QACSPCSSQS 3390 SSSGICTDFW 3400 DLLVKLDNMN 3410 VSRKGKNSVK 3420 SVPVSSGGEG 3430 ETSPHSLEAS 3440 PLGQLMNMLS 3450 HPVIRRSSLL 3460 TEKLLRLLSL 3470 ISIALPENKV 3480 SEVQTNSSNS 3490 GSSTAATSNT 3500 STTTTTTTTA 3510 TAPTPTPPAA 3520 TTPVTSAPAL 3530 VAATAISTIT 3540 VAASTTVTTP 3550 TTATTTVSTS 3560 TTKGSKSPAK 3570 VGEGGSGIDF 3580 KMVSSGLTEN 3590 QLQLSVEVLT 3600 SHSCSEEGLE 3610 DAANVLLQLS 3620 RGDSGTRDTV 3630 LKLLLNGARH 3640 LGYTLCKQIG 3650 TLLAELREYN 3660 LEQQRRAQCE 3670 TLSPDGLPEE 3680 QPQTTKLKGK 3690 MQSRFDMAEN 3700 VVIVASQKRP 3710 LGGRELQLPS 3720 MSMLTSKTST 3730 QKFFLRVLQV 3740 IIQLRDDTRR 3750 ANKKAKQTGR 3760 LGSSGLGSAS 3770 SIQAAVRQLE 3780 AEADAIIQMV 3790 REGQRARRQQ 3800 QAATSESSNQ 3810 SETSVRREES 3820 PMDVDQPSPS 3830 AQDTQSIVIS 3840 DGTPQGEKEK 3850 EEKPPELPLL 3860 SEQLSLDELW 3870 DMLGECLKEL 3880 EESHDQHAVL 3890 VLQPAVEAFF 3900 LVHATERESK 3910 PPVRDTRESQ 3920 LAHIKDEPPP 3930 LSPAPLTPAT 3940 PSSLDPFFSR 3950 EPSSMHISSS 3960 LPPDTQKFLR 3970 FAETHRTVLN 3980 QILRQSTTHL 3990 ADGPFAVLVD 4000 YIRVLDFDVK 4010 RKYFRQELER 4020 LDEGLRKEDM 4030 AVHVRRDHVF 4040 EDSYRELHRK 4050 SPEEMKNRLY 4060 IVFEGEEGQD 4070 AGGLLREWYM 4080 IISREMFNPM 4090 YALFRTSPGD 4100 RVTYTINPSS 4110 HCNPNHLSYF 4120 KFVGRIVAKA 4130 VYDNRLLECY 4140 FTRSFYKHIL 4150 GKSVRYTDME 4160 SEDYHFYQGL 4170 VYLLENDVST 4180 LGYDLTFSTE 4190 VQEFGVCEVR 4200 DLKPNGANIL 4210 VTEENKKEYV 4220 HLVCQMRMTG 4230 AIRKQLAAFL 4240 EGFYEIIPKR 4250 LISIFTEQEL 4260 ELLISGLPTI 4270 DIDDLKSNTE 4280 YHKYQSNSIQ 4290 IQWFWRALRS 4300 FDQADRAKFL 4310 QFVTGTSKVP 4320 LQGFAALEGM 4330 NGIQKFQIHR 4340 DDRSTDRLPS 4350 AHTCFNQLDL 4360 PAYESFEKLR 4370 HMLLLAIQEC SEGFGLA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0000139 Golgi membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0097229 sperm end piece
Cellular Component GO:0097225 sperm midpiece
Cellular Component GO:0097228 sperm principal piece
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0140852 histone ubiquitin ligase activity
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
Molecular Function GO:0034450 ubiquitin-ubiquitin ligase activity
Biological Process GO:0006284 base-excision repair
Biological Process GO:0007249 canonical NF-kappaB signal transduction
Biological Process GO:0030154 cell differentiation
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0042742 defense response to bacterium
Biological Process GO:0007030 Golgi organization
Biological Process GO:0061025 membrane fusion
Biological Process GO:0043124 negative regulation of canonical NF-kappaB signal transduction
Biological Process GO:0010637 negative regulation of mitochondrial fusion
Biological Process GO:0035359 negative regulation of peroxisome proliferator activated receptor signaling pathway
Biological Process GO:0035357 peroxisome proliferator activated receptor signaling pathway
Biological Process GO:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:0031398 positive regulation of protein ubiquitination
Biological Process GO:1905091 positive regulation of type 2 mitophagy
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0141198 protein branched polyubiquitination
Biological Process GO:0070936 protein K48-linked ubiquitination
Biological Process GO:0006513 protein monoubiquitination
Biological Process GO:0000209 protein polyubiquitination
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process

Reference

[1] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.