Search Results

Overview

Uniprot IDQ63HN8
Protein NameE3 ubiquitin-protein ligase RNF213
Gene NameRNF213
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
2276 TSDQSPGKHMVTMDG
297 KEKTQRMKQPPATTP
509 KPHGRLQKVMNHITD

Function

Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115, PubMed:39375464). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Also functions as an intracellular sensor for ISGylated proteins: upon type I interferon stimulation, undergoes ISGylation and oligomerizes on lipid droplets to form a binding platform for ISG15-modified substrate proteins, thereby acting as a broad-spectrum antimicrobial effector. Restricts intracellular bacterial pathogens, such as Listeria monocytogenes, in an ISG15-dependent manner by decorating the bacterial surface with ubiquitin to promote autophagic clearance (PubMed:34599178). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115)

Protein Sequence

10 MECPSCQHVS 20 KEETPKFCSQ 30 CGERLPPAAP 40 IADSENNNST 50 MASASEGEME 60 CGQELKEEGG 70 PCLFPGSDSW 80 QENPEEPCSK 90 ASWTVQESKK 100 KKRKKKKKGN 110 KSASSELASL 120 PLSPASPCHL 130 TLLSNPWPQD 140 TALPHSQAQQ 150 SGPTGQPSQP 160 PGTATTPLEG 170 DGLSAPTEVG 180 DSPLQAQALG 190 EAGVATGSEA 200 QSSPQFQDHT 210 EGEDQDASIP 220 SGGRGLSQEG 230 TGPPTSAGEG 240 HSRTEDAAQE 250 LLLPESKGGS 260 SEPGTELQTT 270 EQQAGASASM 280 AVDAVAEPAN 290 AVKGAGKEMK 300 EKTQRMKQPP 310 ATTPPFKTHC 320 QEAETKTKDE 330 MAAAEEKVGK 340 NEQGEPEDLK 350 KPEGKNRSAA 360 AVKNEKEQKN 370 QEADVQEVKA 380 STLSPGGGVT 390 VFFHAIISLH 400 FPFNPDLHKV 410 FIRGGEEFGE 420 SKWDSNICEL 430 HYTRDLGHDR 440 VLVEGIVCIS 450 KKHLDKYIPY 460 KYVIYNGESF 470 EYEFIYKHQQ 480 KKGEYVNRCL 490 FIKSSLLGSG 500 DWHQYYDIVY 510 MKPHGRLQKV 520 MNHITDGPRK 530 DLVKGKQIAA 540 ALMLDSTFSI 550 LQTWDTINLN 560 SFFTQFEQFC 570 FVLQQPMIYE 580 GQAQLWTDLQ 590 YREKEVKRYL 600 WQHLKKHVVP 610 LPDGKSTDFL 620 PVDCPVRSKL 630 KTGLIVLFVV 640 EKIELLLEGS 650 LDWLCHLLTS 660 DASSPDEFHR 670 DLSHILGIPQ 680 SWRLYLVNLC 690 QRCMDTRTYT 700 WLGALPVLHC 710 CMELAPRHKD 720 AWRQPEDTWA 730 ALEGLSFSPF 740 REQMLDTSSL 750 LQFMREKQHL 760 LSIDEPLFRS 770 WFSLLPLSHL 780 VMYMENFIEH 790 LGRFPAHILD 800 CLSGIYYRLP 810 GLEQVLNTQD 820 VQDVQNVQNI 830 LEMLLRLLDT 840 YRDKIPEEAL 850 SPSYLTVCLK 860 LHEAICSSTK 870 LLKFYELPAL 880 SAEIVCRMIR 890 LLSLVDSAGQ 900 RDETGNNSVQ 910 TVFQGTLAAT 920 KRWLREVFTK 930 NMLTSSGASF 940 TYVKEIEVWR 950 RLVEIQFPAE 960 HGWKESLLGD 970 MEWRLTKEEP 980 LSQITAYCNS 990 CWDTKGLEDS 1000 VAKTFEKCII 1010 EAVSSACQSQ 1020 TSILQGFSYS 1030 DLRKFGIVLS 1040 AVITKSWPRT 1050 ADNFNDILKH 1060 LLTLADVKHV 1070 FRLCGTDEKI 1080 LANVTEDAKR 1090 LIAVADSVLT 1100 KVVGDLLSGT 1110 ILVGQLELII 1120 KHKNQFLDIW 1130 QLREKSLSPQ 1140 DEQCAVEEAL 1150 DWRREELLLL 1160 KKEKRCVDSL 1170 LKMCGNVKHL 1180 IQVDFGVLAV 1190 RHSQDLSSKR 1200 LNDTVTVRLS 1210 TSSNSQRATH 1220 YHLSSQVQEM 1230 AGKIDLLRDS 1240 HIFQLFWREA 1250 AEPLSEPKED 1260 QEAAELLSEP 1270 EEESERHILE 1280 LEEVYDYLYQ 1290 PSYRKFIKLH 1300 QDLKSGEVTL 1310 AEIDVIFKDF 1320 VNKYTDLDSE 1330 LKIMCTVDHQ 1340 DQRDWIKDRV 1350 EQIKEYHHLH 1360 QAVHAAKVIL 1370 QVKESLGLNG 1380 DFSVLNTLLN 1390 FTDNFDDFRR 1400 ETLDQINQEL 1410 IQAKKLLQDI 1420 SEARCKGLQA 1430 LSLRKEFICW 1440 VREALGGINE 1450 LKVFVDLASI 1460 SAGENDIDVD 1470 RVACFHDAVQ 1480 GYASLLFKLD 1490 PSVDFSAFMK 1500 HLKKLWKALD 1510 KDQYLPRKLC 1520 DSARNLEWLK 1530 TVNESHGSVE 1540 RSSLTLATAI 1550 NQRGIYVIQA 1560 PKGGQKISPD 1570 TVLHLILPES 1580 PGSHEESREY 1590 SLEEVKELLN 1600 KLMLMSGKKD 1610 RNNTEVERFS 1620 EVFCSVQRLS 1630 QAFIDLHSAG 1640 NMLFRTWIAM 1650 AYCSPKQGVS 1660 LQMDFGLDLV 1670 TELKEGGDVT 1680 ELLAALCRQM 1690 EHFLDSWKRF 1700 VTQKRMEHFY 1710 LNFYTAEQLV 1720 YLSTELRKQP 1730 PSDAALTMLS 1740 FIKSNCTLRD 1750 VLRASVGCGS 1760 EAARYRMRRV 1770 MEELPLMLLS 1780 EFSLVDKLRI 1790 IMEQSMRCLP 1800 AFLPDCLDLE 1810 TLGHCLAHLA 1820 GMGGSPVERC 1830 LPRGLQVGQP 1840 NLVVCGHSEV 1850 LPAALAVYMQ 1860 TPSQPLPTYD 1870 EVLLCTPATT 1880 FEEVALLLRR 1890 CLTLGSLGHK 1900 VYSLLFADQL 1910 SYEVARQAEE 1920 LFHNLCTQQH 1930 REDYQLVMVC 1940 DGDWEHCYLP 1950 SAFSQHKVFV 1960 TPQAPLEAIQ 1970 AYLAGHYRVP 1980 KQTLSAAAVF 1990 NDRLCVGIVA 2000 SERAGVGKSL 2010 YVKRLHDKMK 2020 MQLNVKNVPL 2030 KTIRLIDPQV 2040 DESRVLGALL 2050 PFLDAQYQKV 2060 PVLFHLDVTS 2070 SVQTGIWVFL 2080 FKLLILQYLM 2090 DINGKMWLRN 2100 PCHLYIVEIL 2110 ERRTSVPSRS 2120 SSALRTRVPQ 2130 FSFLDIFPKV 2140 TCRPPKEVID 2150 MELSALRSDT 2160 EPGMDLWEFC 2170 SETFQRPYQY 2180 LRRFNQNQDL 2190 DTFQYQEGSV 2200 EGTPEECLQH 2210 FLFHCGVINP 2220 SWSELRNFAR 2230 FLNYQLRDCE 2240 ASLFCNPSFI 2250 GDTLRGFKKF 2260 VVTFMIFMAR 2270 DFATPSLHTS 2280 DQSPGKHMVT 2290 MDGVREEDLA 2300 PFSLRKRWES 2310 EPHPYVFFND 2320 DHTTMTFIGF 2330 HLQPNINGSV 2340 DAISHLTGKV 2350 IKRDVMTRDL 2360 YQGLLLQRVP 2370 FNVDFDKLPR 2380 HKKLERLCLT 2390 LGIPQATDPD 2400 KTYELTTDNM 2410 LKILAIEMRF 2420 RCGIPVIIMG 2430 ETGCGKTRLI 2440 KFLSDLRRGG 2450 TNADTIKLVK 2460 VHGGTTADMI 2470 YSRVREAENV 2480 AFANKDQHQL 2490 DTILFFDEAN 2500 TTEAISCIKE 2510 VLCDHMVDGQ 2520 PLAEDSGLHI 2530 IAACNPYRKH 2540 SEEMICRLES 2550 AGLGYRVSME 2560 ETADRLGSIP 2570 LRQLVYRVHA 2580 LPPSLIPLVW 2590 DFGQLSDVAE 2600 KLYIQQIVQR 2610 LVESISLDEN 2620 GTRVITEVLC 2630 ASQGFMRKTE 2640 DECSFVSLRD 2650 VERCVKVFRW 2660 FHEHSAMLLA 2670 QLNAFLSKSS 2680 VSKNHTERDP 2690 VLWSLMLAIG 2700 VCYHASLEKK 2710 DSYRKAIARF 2720 FPKPYDDSRL 2730 LLDEITRAQD 2740 LFLDGVPLRK 2750 TIAKNLALKE 2760 NVFMMVVCIE 2770 LKIPLFLVGK 2780 PGSSKSLAKT 2790 IVADAMQGPA 2800 AYSDLFRSLK 2810 QVHLVSFQCS 2820 PHSTPQGIIS 2830 TFRQCARFQQ 2840 GKDLQQYVSV 2850 VVLDEVGLAE 2860 DSPKMPLKTL 2870 HPLLEDGCIE 2880 DDPAPHKKVG 2890 FVGISNWALD 2900 PAKMNRGIFV 2910 SRGSPNETEL 2920 IESAKGICSS 2930 DILVQDRVQG 2940 YFASFAKAYE 2950 TVCKRQDKEF 2960 FGLRDYYSLI 2970 KMVFAAAKAS 2980 NRKPSPQDIA 2990 QAVLRNFSGK 3000 DDIQALDIFL 3010 ANLPEAKCSE 3020 EVSPMQLIKQ 3030 NIFGPSQKVP 3040 GGEQEDAESR 3050 YLLVLTKNYV 3060 ALQILQQTFF 3070 EGDQQPEIIF 3080 GSGFPKDQEY 3090 TQLCRNINRV 3100 KICMETGKMV 3110 LLLNLQNLYE 3120 SLYDALNQYY 3130 VHLGGQKYVD 3140 LGLGTHRVKC 3150 RVHPNFRLIV 3160 IEEKDVVYKH 3170 FPIPLINRLE 3180 KHYLDINTVL 3190 EKWQKSIVEE 3200 LCAWVEKFIN 3210 VKAHHFQKRH 3220 KYSPSDVFIG 3230 YHSDACASVV 3240 LQVIERQGPR 3250 ALTEELHQKV 3260 SEEAKSILLN 3270 CATPDAVVRL 3280 SAYSLGGFAA 3290 EWLSQEYFHR 3300 QRHNSFADFL 3310 QAHLHTADLE 3320 RHAIFTEITT 3330 FSRLLTSHDC 3340 EILESEVTGR 3350 APKPTLLWLQ 3360 QFDTEYSFLK 3370 EVRNCLTNTA 3380 KCKILIFQTD 3390 FEDGIRSAQL 3400 IASAKYSVIN 3410 EINKIRENED 3420 RIFVYFITKL 3430 SRVGRGTAYV 3440 GFHGGLWQSV 3450 HIDDLRRSTL 3460 MVSDVTRLQH 3470 VTISQLFAPG 3480 DLPELGLEHR 3490 AEDGHEEAME 3500 TEASTSGEVA 3510 EVAEEAMETE 3520 SSEKVGKETS 3530 ELGGSDVSIL 3540 DTTRLLRSCV 3550 QSAVGMLRDQ 3560 NESCTRNMRR 3570 VVLLLGLLNE 3580 DDACHASFLR 3590 VSKMRLSVFL 3600 KKQEESQFHP 3610 LEWLAREACN 3620 QDALQEAGTF 3630 RHTLWKRVQG 3640 AVTPLLASMI 3650 SFIDRDGNLE 3660 LLTRPDTPPW 3670 ARDLWMFIFS 3680 DTMLLNIPLV 3690 MNNERHKGEM 3700 AYIVVQNHMN 3710 LSENASNNVP 3720 FSWKIKDYLE 3730 ELWVQAQYIT 3740 DAEGLPKKFV 3750 DIFQQTPLGR 3760 FLAQLHGEPQ 3770 QELLQCYLKD 3780 FILLTMRVST 3790 EEELKFLQMA 3800 LWSCTRKLKA 3810 ASEAPEEEVS 3820 LPWVHLAYQR 3830 FRSRLQNFSR 3840 ILTIYPQVLH 3850 SLMEARWNHE 3860 LAGCEMTLDA 3870 FAAMACTEML 3880 TRNTLKPSPQ 3890 AWLQLVKNLS 3900 MPLELICSDE 3910 HMQGSGSLAQ 3920 AVIREVRAQW 3930 SRIFSTALFV 3940 EHVLLGTESR 3950 VPELQGLVTE 3960 HVFLLDKCLR 3970 ENSDVKTHGP 3980 FEAVMRTLCE 3990 CKETASKTLS 4000 RFGIQPCSIC 4010 LGDAKDPVCL 4020 PCDHVHCLRC 4030 LRAWFASEQM 4040 ICPYCLTALP 4050 DEFSPAVSQA 4060 HREAIEKHAR 4070 FRQMCNSFFV 4080 DLVSTICFKD 4090 NAPPEKEVIE 4100 SLLSLLFVQK 4110 GRLRDAAQRH 4120 CEHTKSLSPF 4130 NDVVDKTPVI 4140 RSVILKLLLK 4150 YSFHDVKDYI 4160 QEYLTLLKKK 4170 AFITEDKTEL 4180 YMLFINCLED 4190 SILEKTSAYS 4200 RNDELNHLEE 4210 EGRFLKAYSP 4220 ASRGREPANE 4230 ASVEYLQEVA 4240 RIRLCLDRAA 4250 DFLSEPEGGP 4260 EMAKEKQCYL 4270 QQVKQFCIRV 4280 ENDWHRVYLV 4290 RKLSSQRGME 4300 FVQGLSKPGR 4310 PHQWVFPKDV 4320 VKQQGLRQDH 4330 PGQMDRYLVY 4340 GDEYKALRDA 4350 VAKAVLECKP 4360 LGIKTALKAC 4370 KTPQSQQSAY 4380 FLLTLFREVA 4390 ILYRSHNASL 4400 HPTPEQCEAV 4410 SKFIGECKIL 4420 SPPDISRFAT 4430 SLVDNSVPLL 4440 RAGPSDSNLD 4450 GTVTEMAIHA 4460 AAVLLCGQNE 4470 LLEPLKNLAF 4480 SPATMAHAFL 4490 PTMPEDLLAQ 4500 ARRWKGLERV 4510 HWYTCPNGHP 4520 CSVGECGRPM 4530 EQSICIDCHA 4540 PIGGIDHKPR 4550 DGFHLVKDKA 4560 DRTQTGHVLG 4570 NPQRRDVVTC 4580 DRGLPPVVFL 4590 LIRLLTHLAL 4600 LLGASQSSQA 4610 LINIIKPPVR 4620 DPKGFLQQHI 4630 LKDLEQLAKM 4640 LGHSADETIG 4650 VVHLVLRRLL 4660 QEQHQLSSRR 4670 LLNFDTELST 4680 KEMRNNWEKE 4690 IAAVISPELE 4700 HLDKTLPTMN 4710 NLISQDKRIS 4720 SNPVAKIIYG 4730 DPVTFLPHLP 4740 RKSVVHCSKI 4750 WSCRKRITVE 4760 YLQHIVEQKN 4770 GKERVPILWH 4780 FLQKEAELRL 4790 VKFLPEILAL 4800 QRDLVKQFQN 4810 VQQVEYSSIR 4820 GFLSKHSSDG 4830 LRQLLHNRIT 4840 VFLSTWNKLR 4850 RSLETNGEIN 4860 LPKDYCSTDL 4870 DLDTEFEILL 4880 PRRRGLGLCA 4890 TALVSYLIRL 4900 HNEIVYAVEK 4910 LSKENNSYSV 4920 DAAEVTELHV 4930 ISYEVERDLT 4940 PLILSNCQYQ 4950 VEEGRETVQE 4960 FDLEKIQRQI 4970 VSRFLQGKPR 4980 LSLKGIPTLV 4990 YRHDWNYEHL 5000 FMDIKNKMAQ 5010 DSLPSSVISA 5020 ISGQLQSYSD 5030 ACEVLSVVEV 5040 TLGFLSTAGG 5050 DPNMQLNVYT 5060 QDILQMGDQT 5070 IHVLKALNRC 5080 QLKHTIALWQ 5090 FLSAHKSEQL 5100 LRLHKEPFGE 5110 ISSRYKADLS 5120 PENAKLLSTF 5130 LNQTGLDAFL 5140 LELHEMIILK 5150 LKNPQTQTEE 5160 RFRPQWSLRD 5170 TLVSYMQTKE 5180 SEILPEMASQ 5190 FPEEILLASC 5200 VSVWKTAAVL KWNREMR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005811 lipid droplet
Cellular Component GO:0016020 membrane
Cellular Component GO:0005730 nucleolus
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0001525 angiogenesis
Biological Process GO:0042742 defense response to bacterium
Biological Process GO:0002376 immune system process
Biological Process GO:0140042 lipid droplet formation
Biological Process GO:0120323 lipid ubiquitination
Biological Process GO:2000051 negative regulation of non-canonical Wnt signaling pathway
Biological Process GO:0051865 protein autoubiquitination
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0019216 regulation of lipid metabolic process
Biological Process GO:0002040 sprouting angiogenesis
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process
Biological Process GO:0098792 xenophagy

Reference

[1] 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.

[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[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.