Search Results

Overview

Uniprot IDQ5T4S7
Protein NameE3 ubiquitin-protein ligase UBR4
Gene NameUBR4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
436 LADKGKEKDPLAALR
452 RDILSRTKEGVGSPK
4814 LGMTTNEKGQVVTKT
4820 EKGQVVTKTALLKQM
5085 RLTDKAVKDYSAYRS

Function

E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the silencing factor of the integrated stress response (SIFI) complex, a multiprotein complex that turns off the mitochondrial stress response after a specific stress event has been resolved (PubMed:38297121, PubMed:40328314, PubMed:40875847). The SIFI complex ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors such as ABHD10 (PubMed:38297121, PubMed:40328314). Within the SIFI complex, UBR4 initiates ubiquitin chains that are further elongated or branched by KCMF1 (PubMed:38297121, PubMed:40328314, PubMed:40875847). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886)

Protein Sequence

10 MATSGGEEAA 20 AAAPAPGTPA 30 TGADTTPGWE 40 VAVRPLLSAS 50 YSAFEMKELP 60 QLVASVIESE 70 SEILHHEKQY 80 EPFYSSFVAL 90 STHYITTVCS 100 LIPRNQLQSV 110 AAACKVLIEF 120 SLLRLENPDE 130 ACAVSQKHLI 140 LLIKGLCTGC 150 SRLDRTEIIT 160 FTAMMKSAKL 170 PQTVKTLSDV 180 EDQKELASPV 190 SPELRQKEVQ 200 MNFLNQLTSV 210 FNPRTVASQP 220 ISTQTLVEGE 230 NDEQSSTDQA 240 SAIKTKNVFI 250 AQNVASLQEL 260 GGSEKLLRVC 270 LNLPYFLRYI 280 NRFQDAVLAN 290 SFFIMPATVA 300 DATAVRNGFH 310 SLVIDVTMAL 320 DTLSLPVLEP 330 LNPSRLQDVT 340 VLSLSCLYAG 350 VSVATCMAIL 360 HVGSAQQVRT 370 GSTSSKEDDY 380 ESDAATIVQK 390 CLEIYDMIGQ 400 AISSSRRAGG 410 EHYQNFQLLG 420 AWCLLNSLFL 430 ILNLSPTALA 440 DKGKEKDPLA 450 ALRVRDILSR 460 TKEGVGSPKL 470 GPGKGHQGFG 480 VLSVILANHA 490 IKLLTSLFQD 500 LQVEALHKGW 510 ETDGPPAALS 520 IMAQSTSIQR 530 IQRLIDSVPL 540 MNLLLTLLST 550 SYRKACVLQR 560 QRKGSMSSDA 570 SASTDSNTYY 580 EDDFSSTEED 590 SSQDDDSEPI 600 LGQWFEETIS 610 PSKEKAAPPP 620 PPPPPPLESS 630 PRVKSPSKQA 640 PGEKGNILAS 650 RKDPELFLGL 660 ASNILNFITS 670 SMLNSRNNFI 680 RNYLSVSLSE 690 HHMATLASII 700 KEVDKDGLKG 710 SSDEEFAAAL 720 YHFNHSLVTS 730 DLQSPNLQNT 740 LLQQLGVAPF 750 SEGPWPLYIH 760 PQSLSVLSRL 770 LLIWQHKASA 780 QGDPDVPECL 790 KVWDRFLSTM 800 KQNALQGVVP 810 SETEDLNVEH 820 LQMLLLIFHN 830 FTETGRRAIL 840 SLFVQIIQEL 850 SVNMDAQMRF 860 VPLILARLLL 870 IFDYLLHQYS 880 KAPVYLFEQV 890 QHNLLSPPFG 900 WASGSQDSNS 910 RRATTPLYHG 920 FKEVEENWSK 930 HFSSDAVPHP 940 RFYCVLSPEA 950 SEDDLNRLDS 960 VACDVLFSKL 970 VKYDELYAAL 980 TALLAAGSQL 990 DTVRRKENKN 1000 VTALEACALQ 1010 YYFLILWRIL 1020 GILPPSKTYI 1030 NQLSMNSPEM 1040 SECDILHTLR 1050 WSSRLRISSY 1060 VNWIKDHLIK 1070 QGMKAEHASS 1080 LLELASTTKC 1090 SSVKYDVEIV 1100 EEYFARQISS 1110 FCSIDCTTIL 1120 QLHEIPSLQS 1130 IYTLDAAISK 1140 VQVSLDEHFS 1150 KMAAETDPHK 1160 SSEITKNLLP 1170 ATLQLIDTYA 1180 SFTRAYLLQN 1190 FNEEGTTEKP 1200 SKEKLQGFAA 1210 VLAIGSSRCK 1220 ANTLGPTLVQ 1230 NLPSSVQTVC 1240 ESWNNINTNE 1250 FPNIGSWRNA 1260 FANDTIPSES 1270 YISAVQAAHL 1280 GTLCSQSLPL 1290 AASLKHTLLS 1300 LVRLTGDLIV 1310 WSDEMNPPQV 1320 IRTLLPLLLE 1330 SSTESVAEIS 1340 SNSLERILGP 1350 AESDEFLARV 1360 YEKLITGCYN 1370 ILANHADPNS 1380 GLDESILEEC 1390 LQYLEKQLES 1400 SQARKAMEEF 1410 FSDSGELVQI 1420 MMATANENLS 1430 AKFCNRVLKF 1440 FTKLFQLTEK 1450 SPNPSLLHLC 1460 GSLAQLACVE 1470 PVRLQAWLTR 1480 MTTSPPKDSD 1490 QLDVIQENRQ 1500 LLQLLTTYIV 1510 RENSQVGEGV 1520 CAVLLGTLTP 1530 MATEMLANGD 1540 GTGFPELMVV 1550 MATLASAGQG 1560 AGHLQLHNAA 1570 VDWLSRCKKY 1580 LSQKNVVEKL 1590 NANVMHGKHV 1600 MILECTCHIM 1610 SYLADVTNAL 1620 SQSNGQGPSH 1630 LSVDGEERAI 1640 EVDSDWVEEL 1650 AVEEEDSQAE 1660 DSDEDSLCNK 1670 LCTFTITQKE 1680 FMNQHWYHCH 1690 TCKMVDGVGV 1700 CTVCAKVCHK 1710 DHEISYAKYG 1720 SFFCDCGAKE 1730 DGSCLALVKR 1740 TPSSGMSSTM 1750 KESAFQSEPR 1760 ISESLVRHAS 1770 TSSPADKAKV 1780 TISDGKVADE 1790 EKPKKSSLCR 1800 TVEGCREELQ 1810 NQANFSFAPL 1820 VLDMLNFLMD 1830 AIQTNFQQAS 1840 AVGSSSRAQQ 1850 ALSELHTVEK 1860 AVEMTDQLMV 1870 PTLGSQEGAF 1880 ENVRMNYSGD 1890 QGQTIRQLIS 1900 AHVLRRVAMC 1910 VLSSPHGRRQ 1920 HLAVSHEKGK 1930 ITVLQLSALL 1940 KQADSSKRKL 1950 TLTRLASAPV 1960 PFTVLSLTGN 1970 PCKEDYLAVC 1980 GLKDCHVLTF 1990 SSSGSVSDHL 2000 VLHPQLATGN 2010 FIIKAVWLPG 2020 SQTELAIVTA 2030 DFVKIYDLCV 2040 DALSPTFYFL 2050 LPSSKIRDVT 2060 FLFNEEGKNI 2070 IVIMSSAGYI 2080 YTQLMEEASS 2090 AQQGPFYVTN 2100 VLEINHEDLK 2110 DSNSQVAGGG 2120 VSVYYSHVLQ 2130 MLFFSYCQGK 2140 SFAATISRTT 2150 LEVLQLFPIN 2160 IKSSNGGSKT 2170 SPALCQWSEV 2180 MNHPGLVCCV 2190 QQTTGVPLVV 2200 MVKPDTFLIQ 2210 EIKTLPAKAK 2220 IQDMVAIRHT 2230 ACNEQQRTTM 2240 ILLCEDGSLR 2250 IYMANVENTS 2260 YWLQPSLQPS 2270 SVISIMKPVR 2280 KRKTATITTR 2290 TSSQVTFPID 2300 FFEHNQQLTD 2310 VEFGGNDLLQ 2320 VYNAQQIKHR 2330 LNSTGMYVAN 2340 TKPGGFTIEI 2350 SNNNSTMVMT 2360 GMRIQIGTQA 2370 IERAPSYIEI 2380 FGRTMQLNLS 2390 RSRWFDFPFT 2400 REEALQADKK 2410 LNLFIGASVD 2420 PAGVTMIDAV 2430 KIYGKTKEQF 2440 GWPDEPPEEF 2450 PSASVSNICP 2460 SNLNQSNGTG 2470 DSDSAAPTTT 2480 SGTVLERLVV 2490 SSLEALESCF 2500 AVGPIIEKER 2510 NKNAAQELAT 2520 LLLSLPAPAS 2530 VQQQSKSLLA 2540 SLHTSRSAYH 2550 SHKDQALLSK 2560 AVQCLNTSSK 2570 EGKDLDPEVF 2580 QRLVITARSI 2590 AIMRPNNLVH 2600 FTESKLPQME 2610 TEGMDEGKEP 2620 QKQLEGDCCS 2630 FITQLVNHFW 2640 KLHASKPKNA 2650 FLAPACLPGL 2660 THIEATVNAL 2670 VDIIHGYCTC 2680 ELDCINTASK 2690 IYMQMLLCPD 2700 PAVSFSCKQA 2710 LIRVLRPRNK 2720 RRHVTLPSSP 2730 RSNTPMGDKD 2740 DDDDDDADEK 2750 MQSSGIPNGG 2760 HIRQESQEQS 2770 EVDHGDFEMV 2780 SESMVLETAE 2790 NVNNGNPSPL 2800 EALLAGAEGF 2810 PPMLDIPPDA 2820 DDETMVELAI 2830 ALSLQQDQQG 2840 SSSSALGLQS 2850 LGLSGQAPSS 2860 SSLDAGTLSD 2870 TTASAPASDD 2880 EGSTAATDGS 2890 TLRTSPADHG 2900 GSVGSESGGS 2910 AVDSVAGEHS 2920 VSGRSSAYGD 2930 ATAEGHPAGP 2940 GSVSSSTGAI 2950 STTTGHQEGD 2960 GSEGEGEGET 2970 EGDVHTSNRL 2980 HMVRLMLLER 2990 LLQTLPQLRN 3000 VGGVRAIPYM 3010 QVILMLTTDL 3020 DGEDEKDKGA 3030 LDNLLSQLIA 3040 ELGMDKKDVS 3050 KKNERSALNE 3060 VHLVVMRLLS 3070 VFMSRTKSGS 3080 KSSICESSSL 3090 ISSATAAALL 3100 SSGAVDYCLH 3110 VLKSLLEYWK 3120 SQQNDEEPVA 3130 TSQLLKPHTT 3140 SSPPDMSPFF 3150 LRQYVKGHAA 3160 DVFEAYTQLL 3170 TEMVLRLPYQ 3180 IKKITDTNSR 3190 IPPPVFDHSW 3200 FYFLSEYLMI 3210 QQTPFVRRQV 3220 RKLLLFICGS 3230 KEKYRQLRDL 3240 HTLDSHVRGI 3250 KKLLEEQGIF 3260 LRASVVTASS 3270 GSALQYDTLI 3280 SLMEHLKACA 3290 EIAAQRTINW 3300 QKFCIKDDSV 3310 LYFLLQVSFL 3320 VDEGVSPVLL 3330 QLLSCALCGS 3340 KVLAALAASS 3350 GSSSASSSSA 3360 PVAASSGQAT 3370 TQSKSSTKKS 3380 KKEEKEKEKD 3390 GETSGSQEDQ 3400 LCTALVNQLN 3410 KFADKETLIQ 3420 FLRCFLLESN 3430 SSSVRWQAHC 3440 LTLHIYRNSS 3450 KSQQELLLDL 3460 MWSIWPELPA 3470 YGRKAAQFVD 3480 LLGYFSLKTP 3490 QTEKKLKEYS 3500 QKAVEILRTQ 3510 NHILTNHPNS 3520 NIYNTLSGLV 3530 EFDGYYLESD 3540 PCLVCNNPEV 3550 PFCYIKLSSI 3560 KVDTRYTTTQ 3570 QVVKLIGSHT 3580 ISKVTVKIGD 3590 LKRTKMVRTI 3600 NLYYNNRTVQ 3610 AIVELKNKPA 3620 RWHKAKKVQL 3630 TPGQTEVKID 3640 LPLPIVASNL 3650 MIEFADFYEN 3660 YQASTETLQC 3670 PRCSASVPAN 3680 PGVCGNCGEN 3690 VYQCHKCRSI 3700 NYDEKDPFLC 3710 NACGFCKYAR 3720 FDFMLYAKPC 3730 CAVDPIENEE 3740 DRKKAVSNIN 3750 TLLDKADRVY 3760 HQLMGHRPQL 3770 ENLLCKVNEA 3780 APEKPQDDSG 3790 TAGGISSTSA 3800 SVNRYILQLA 3810 QEYCGDCKNS 3820 FDELSKIIQK 3830 VFASRKELLE 3840 YDLQQREAAT 3850 KSSRTSVQPT 3860 FTASQYRALS 3870 VLGCGHTSST 3880 KCYGCASAVT 3890 EHCITLLRAL 3900 ATNPALRHIL 3910 VSQGLIRELF 3920 DYNLRRGAAA 3930 MREEVRQLMC 3940 LLTRDNPEAT 3950 QQMNDLIIGK 3960 VSTALKGHWA 3970 NPDLASSLQY 3980 EMLLLTDSIS 3990 KEDSCWELRL 4000 RCALSLFLMA 4010 VNIKTPVVVE 4020 NITLMCLRIL 4030 QKLIKPPAPT 4040 SKKNKDVPVE 4050 ALTTVKPYCN 4060 EIHAQAQLWL 4070 KRDPKASYDA 4080 WKKCLPIRGI 4090 DGNGKAPSKS 4100 ELRHLYLTEK 4110 YVWRWKQFLS 4120 RRGKRTSPLD 4130 LKLGHNNWLR 4140 QVLFTPATQA 4150 ARQAACTIVE 4160 ALATIPSRKQ 4170 QVLDLLTSYL 4180 DELSIAGECA 4190 AEYLALYQKL 4200 ITSAHWKVYL 4210 AARGVLPYVG 4220 NLITKEIARL 4230 LALEEATLST 4240 DLQQGYALKS 4250 LTGLLSSFVE 4260 VESIKRHFKS 4270 RLVGTVLNGY 4280 LCLRKLVVQR 4290 TKLIDETQDM 4300 LLEMLEDMTT 4310 GTESETKAFM 4320 AVCIETAKRY 4330 NLDDYRTPVF 4340 IFERLCSIIY 4350 PEENEVTEFF 4360 VTLEKDPQQE 4370 DFLQGRMPGN 4380 PYSSNEPGIG 4390 PLMRDIKNKI 4400 CQDCDLVALL 4410 EDDSGMELLV 4420 NNKIISLDLP 4430 VAEVYKKVWC 4440 TTNEGEPMRI 4450 VYRMRGLLGD 4460 ATEEFIESLD 4470 STTDEEEDEE 4480 EVYKMAGVMA 4490 QCGGLECMLN 4500 RLAGIRDFKQ 4510 GRHLLTVLLK 4520 LFSYCVKVKV 4530 NRQQLVKLEM 4540 NTLNVMLGTL 4550 NLALVAEQES 4560 KDSGGAAVAE 4570 QVLSIMEIIL 4580 DESNAEPLSE 4590 DKGNLLLTGD 4600 KDQLVMLLDQ 4610 INSTFVRSNP 4620 SVLQGLLRII 4630 PYLSFGEVEK 4640 MQILVERFKP 4650 YCNFDKYDED 4660 HSGDDKVFLD 4670 CFCKIAAGIK 4680 NNSNGHQLKD 4690 LILQKGITQN 4700 ALDYMKKHIP 4710 SAKNLDADIW 4720 KKFLSRPALP 4730 FILRLLRGLA 4740 IQHPGTQVLI 4750 GTDSIPNLHK 4760 LEQVSSDEGI 4770 GTLAENLLEA 4780 LREHPDVNKK 4790 IDAARRETRA 4800 EKKRMAMAMR 4810 QKALGTLGMT 4820 TNEKGQVVTK 4830 TALLKQMEEL 4840 IEEPGLTCCI 4850 CREGYKFQPT 4860 KVLGIYTFTK 4870 RVALEEMENK 4880 PRKQQGYSTV 4890 SHFNIVHYDC 4900 HLAAVRLARG 4910 REEWESAALQ 4920 NANTKCNGLL 4930 PVWGPHVPES 4940 AFATCLARHN 4950 TYLQECTGQR 4960 EPTYQLNIHD 4970 IKLLFLRFAM 4980 EQSFSADTGG 4990 GGRESNIHLI 5000 PYIIHTVLYV 5010 LNTTRATSRE 5020 EKNLQGFLEQ 5030 PKEKWVESAF 5040 EVDGPYYFTV 5050 LALHILPPEQ 5060 WRATRVEILR 5070 RLLVTSQARA 5080 VAPGGATRLT 5090 DKAVKDYSAY 5100 RSSLLFWALV 5110 DLIYNMFKKV 5120 PTSNTEGGWS 5130 CSLAEYIRHN 5140 DMPIYEAADK 5150 ALKTFQEEFM 5160 PVETFSEFLD 5170 VAGLLSEITD 5180 PESFLKDLLN SVP

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016020 membrane
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005856 cytoskeleton
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005768 endosome
Cellular Component GO:0101003 ficolin-1-rich granule membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0035579 specific granule membrane
Cellular Component GO:0070821 tertiary granule membrane
Molecular Function GO:0005516 calmodulin binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:1990756 ubiquitin-like ligase-substrate adaptor activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0140455 cytoplasm protein quality control
Biological Process GO:0071629 cytoplasm protein quality control by the ubiquitin-proteasome system
Biological Process GO:0007032 endosome organization
Biological Process GO:0140468 HRI-mediated signaling
Biological Process GO:0045717 negative regulation of fatty acid biosynthetic process
Biological Process GO:0141191 negative regulation of HRI-mediated signaling
Biological Process GO:0010508 positive regulation of autophagy
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0141198 protein branched polyubiquitination
Biological Process GO:0070979 protein K11-linked ubiquitination
Biological Process GO:0044314 protein K27-linked ubiquitination
Biological Process GO:0070936 protein K48-linked ubiquitination
Biological Process GO:0006515 protein quality control for misfolded or incompletely synthesized proteins
Biological Process GO:0006979 response to oxidative stress
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process
Biological Process GO:0071596 ubiquitin-dependent protein catabolic process via the N-end rule pathway

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] 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.