Search Results

Overview

Uniprot IDQ7Z6Z7
Protein NameE3 ubiquitin-protein ligase HUWE1
Gene NameHUWE1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
2267 PSSLFGSKSASSKNK
3257 EKGKKSSKSCGSSSH
3558 KGSKSPAKVSDGGSS
3675 EEQPQTTKLKGKMQS

Function

E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). 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 (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquitination and degradation of NR1D1 (PubMed:20534529). 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 (PubMed:35776542). 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 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity)

Protein Sequence

10 MKVDRTKLKK 20 TPTEAPADCR 30 ALIDKLKVCN 40 DEQLLLELQQ 50 IKTWNIGKCE 60 LYHWVDLLDR 70 FDGILADAGQ 80 TVENMSWMLV 90 CDRPEREQLK 100 MLLLAVLNFT 110 ALLIEYSFSR 120 HLYSSIEHLT 130 TLLASSDMQV 140 VLAVLNLLYV 150 FSKRSNYITR 160 LGSDKRTPLL 170 TRLQHLAESW 180 GGKENGFGLA 190 ECCRDLHMMK 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 RPNTTQEGEE 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 FNSTQQNETE 760 PNQQVVGTEE 770 RIPIPLMDYI 780 LNVMKFVESI 790 LSNNTTDDHC 800 QEFVNQKGLL 810 PLVTILGLPN 820 LPIDFPTSAA 830 CQAVAGVCKS 840 ILTLSHEPKV 850 LQEGLLQLDS 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 DGEQDGAAGS 1010 MDASTQGLLE 1020 GIGLDGDTLA 1030 PMETDEPTAS 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 QNFPQFSALR 1250 FLVVTQKAAF 1260 TCIKNLWNRK 1270 PLKVYGGRMA 1280 ESMLAILCHI 1290 LRGEPVIRER 1300 LSKEKEGSRG 1310 EEDTGQEEGG 1320 SRREPQVNQQ 1330 QLQQLMDMGF 1340 TREHAMEALL 1350 NTSTMEQATE 1360 YLLTHPPPIM 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 TLLRVPRLNK 1700 NSKNSNGQEL 1710 EKTLEESKEM 1720 DIKRKENKGN 1730 DTPLALESTN 1740 TEKETSLEET 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 KPSPLPVIPD 1950 TIKEVIYDML 1960 NALAAYHAPE 1970 EADKSDPKPG 1980 VMTQEVGQLL 1990 QDMGDDVYQQ 2000 YRSLTRQSSD 2010 FDTQSGFSIN 2020 SQVFAADGAS 2030 TETSASGTSQ 2040 GEASTPEESR 2050 DGKKDKEGDR 2060 ASEEGKQKGK 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 GASQDSSSNQ 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 KVSIVNHLEF 2690 LRDEELEERR 2700 EKRRKQLAEE 2710 ETKITDKGKE 2720 DKENRDQSAQ 2730 CTASKSNDST 2740 EQNLSDGTPM 2750 PDSYPTTPSS 2760 TDAATSESKE 2770 TLGTLQSSQQ 2780 QPTLPTPPAL 2790 GEVPQELQSP 2800 AGEGGSSTQL 2810 LMPVEPEELG 2820 PTRPSGEAET 2830 TQMELSPAPT 2840 ITSLSPERAE 2850 DSDALTAVSS 2860 QLEGSPMDTS 2870 SLASCTLEEA 2880 VGDTSAAGSS 2890 EQPRAGSSTP 2900 GDAPPAVAEV 2910 QGRSDGSGES 2920 AQPPEDSSPP 2930 ASSESSSTRD 2940 SAVAISGADS 2950 RGILEEPLPS 2960 TSSEEEDPLA 2970 GISLPEGVDP 2980 SFLAALPDDI 2990 RREVLQNQLG 3000 IRPPTRTAPS 3010 TNSSAPAVVG 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 ETPKLTTSEE 3260 KGKKSSKSCG 3270 SSSHENRPLD 3280 LLHKMESKSS 3290 NQLSWLSVSM 3300 DAALGCRTNI 3310 FQIQRSGGRK 3320 HTEKHASGGS 3330 TVHIHPQAAP 3340 VVCRHVLDTL 3350 IQLAKVFPSH 3360 FTQQRTKETN 3370 CESDRERGNK 3380 ACSPCSSQSS 3390 SSGICTDFWD 3400 LLVKLDNMNV 3410 SRKGKNSVKS 3420 VPVSAGGEGE 3430 TSPYSLEASP 3440 LGQLMNMLSH 3450 PVIRRSSLLT 3460 EKLLRLLSLI 3470 SIALPENKVS 3480 EAQANSGSGA 3490 SSTTTATSTT 3500 STTTTTAAST 3510 TPTPPTAPTP 3520 VTSAPALVAA 3530 TAISTIVVAA 3540 STTVTTPTTA 3550 TTTVSISPTT 3560 KGSKSPAKVS 3570 DGGSSSTDFK 3580 MVSSGLTENQ 3590 LQLSVEVLTS 3600 HSCSEEGLED 3610 AANVLLQLSR 3620 GDSGTRDTVL 3630 KLLLNGARHL 3640 GYTLCKQIGT 3650 LLAELREYNL 3660 EQQRRAQCET 3670 LSPDGLPEEQ 3680 PQTTKLKGKM 3690 QSRFDMAENV 3700 VIVASQKRPL 3710 GGRELQLPSM 3720 SMLTSKTSTQ 3730 KFFLRVLQVI 3740 IQLRDDTRRA 3750 NKKAKQTGRL 3760 GSSGLGSASS 3770 IQAAVRQLEA 3780 EADAIIQMVR 3790 EGQRARRQQQ 3800 AATSESSQSE 3810 ASVRREESPM 3820 DVDQPSPSAQ 3830 DTQSIASDGT 3840 PQGEKEKEER 3850 PPELPLLSEQ 3860 LSLDELWDML 3870 GECLKELEES 3880 HDQHAVLVLQ 3890 PAVEAFFLVH 3900 ATERESKPPV 3910 RDTRESQLAH 3920 IKDEPPPLSP 3930 APLTPATPSS 3940 LDPFFSREPS 3950 SMHISSSLPP 3960 DTQKFLRFAE 3970 THRTVLNQIL 3980 RQSTTHLADG 3990 PFAVLVDYIR 4000 VLDFDVKRKY 4010 FRQELERLDE 4020 GLRKEDMAVH 4030 VRRDHVFEDS 4040 YRELHRKSPE 4050 EMKNRLYIVF 4060 EGEEGQDAGG 4070 LLREWYMIIS 4080 REMFNPMYAL 4090 FRTSPGDRVT 4100 YTINPSSHCN 4110 PNHLSYFKFV 4120 GRIVAKAVYD 4130 NRLLECYFTR 4140 SFYKHILGKS 4150 VRYTDMESED 4160 YHFYQGLVYL 4170 LENDVSTLGY 4180 DLTFSTEVQE 4190 FGVCEVRDLK 4200 PNGANILVTE 4210 ENKKEYVHLV 4220 CQMRMTGAIR 4230 KQLAAFLEGF 4240 YEIIPKRLIS 4250 IFTEQELELL 4260 ISGLPTIDID 4270 DLKSNTEYHK 4280 YQSNSIQIQW 4290 FWRALRSFDQ 4300 ADRAKFLQFV 4310 TGTSKVPLQG 4320 FAALEGMNGI 4330 QKFQIHRDDR 4340 STDRLPSAHT 4350 CFNQLDLPAY 4360 ESFEKLRHML 4370 LLAIQECSEG FGLA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005576 extracellular region
Cellular Component GO:1904813 ficolin-1-rich granule lumen
Cellular Component GO:0000139 Golgi membrane
Cellular Component GO:0016020 membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0031965 nuclear membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0034774 secretory granule lumen
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0140852 histone ubiquitin ligase activity
Molecular Function GO:0003723 RNA binding
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:0030154 cell differentiation
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0007030 Golgi organization
Biological Process GO:0061025 membrane fusion
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:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:1903955 positive regulation of protein targeting to mitochondrion
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] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.