Search Results

Overview

Uniprot IDO95071
Protein NameE3 ubiquitin-protein ligase UBR5
Gene NameUBR5
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1447 SVEMASSKKKNNFIP

Function

E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). 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 (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, 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: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity)

Protein Sequence

10 MTSIHFVVHP 20 LPGTEDQLND 30 RLREVSEKLN 40 KYNLNSHPPL 50 NVLEQATIKQ 60 CVVGPNHAAF 70 LLEDGRVCRI 80 GFSVQPDRLE 90 LGKPDNNDGS 100 KLNSNSGAGR 110 TSRPGRTSDS 120 PWFLSGSETL 130 GRLAGNTLGS 140 RWSSGVGGSG 150 GGSSGRSSAG 160 ARDSRRQTRV 170 IRTGRDRGSG 180 LLGSQPQPVI 190 PASVIPEELI 200 SQAQVVLQGK 210 SRSVIIRELQ 220 RTNLDVNLAV 230 NNLLSRDDED 240 GDDGDDTASE 250 SYLPGEDLMS 260 LLDADIHSAH 270 PSVIIDADAM 280 FSEDISYFGY 290 PSFRRSSLSR 300 LGSSRVLLLP 310 LERDSELLRE 320 RESVLRLRER 330 RWLDGASFDN 340 ERGSTSKEGE 350 PNLDKKNTPV 360 QSPVSLGEDL 370 QWWPDKDGTK 380 FICIGALYSE 390 LLAVSSKGEL 400 YQWKWSESEP 410 YRNAQNPSLH 420 HPRATFLGLT 430 NEKIVLLSAN 440 SIRATVATEN 450 NKVATWVDET 460 LSSVASKLEH 470 TAQTYSELQG 480 ERIVSLHCCA 490 LYTCAQLENS 500 LYWWGVVPFS 510 QRKKMLEKAR 520 AKNKKPKSSA 530 GISSMPNITV 540 GTQVCLRNNP 550 LYHAGAVAFS 560 ISAGIPKVGV 570 LMESVWNMND 580 SCRFQLRSPE 590 SLKNMEKASK 600 TTEAKPESKQ 610 EPVKTEMGPP 620 PSPASTCSDA 630 SSIASSASMP 640 YKRRRSTPAP 650 KEEEKVNEEQ 660 WSLREVVFVE 670 DVKNVPVGKV 680 LKVDGAYVAV 690 KFPGTSSNTN 700 CQNSSGPDAD 710 PSSLLQDCRL 720 LRIDELQVVK 730 TGGTPKVPDC 740 FQRTPKKLCI 750 PEKTEILAVN 760 VDSKGVHAVL 770 KTGNWVRYCI 780 FDLATGKAEQ 790 ENNFPTSSIA 800 FLGQNERNVA 810 IFTAGQESPI 820 ILRDGNGTIY 830 PMAKDCMGGI 840 RDPDWLDLPP 850 ISSLGMGVHS 860 LINLPANSTI 870 KKKAAVIIMA 880 VEKQTLMQHI 890 LRCDYEACRQ 900 YLMNLEQAVV 910 LEQNLQMLQT 920 FISHRCDGNR 930 NILHACVSVC 940 FPTSNKETKE 950 EEEAERSERN 960 TFAERLSAVE 970 AIANAISVVS 980 SNGPGNRAGS 990 SSSRSLRLRE 1000 MMRRSLRAAG 1010 LGRHEAGASS 1020 SDHQDPVSPP 1030 IAPPSWVPDP 1040 PAMDPDGDID 1050 FILAPAVGSL 1060 TTAATGTGQG 1070 PSTSTIPGPS 1080 TEPSVVESKD 1090 RKANAHFILK 1100 LLCDSVVLQP 1110 YLRELLSAKD 1120 ARGMTPFMSA 1130 VSGRAYPAAI 1140 TILETAQKIA 1150 KAEISSSEKE 1160 EDVFMGMVCP 1170 SGTNPDDSPL 1180 YVLCCNDTCS 1190 FTWTGAEHIN 1200 QDIFECRTCG 1210 LLESLCCCTE 1220 CARVCHKGHD 1230 CKLKRTSPTA 1240 YCDCWEKCKC 1250 KTLIAGQKSA 1260 RLDLLYRLLT 1270 ATNLVTLPNS 1280 RGEHLLLFLV 1290 QTVARQTVEH 1300 CQYRPPRIRE 1310 DRNRKTASPE 1320 DSDMPDHDLE 1330 PPRFAQLALE 1340 RVLQDWNALK 1350 SMIMFGSQEN 1360 KDPLSASSRI 1370 GHLLPEEQVY 1380 LNQQSGTIRL 1390 DCFTHCLIVK 1400 CTADILLLDT 1410 LLGTLVKELQ 1420 NKYTPGRREE 1430 AIAVTMRFLR 1440 SVARVFVILS 1450 VEMASSKKKN 1460 NFIPQPIGKC 1470 KRVFQALLPY 1480 AVEELCNVAE 1490 SLIVPVRMGI 1500 ARPTAPFTLA 1510 STSIDAMQGS 1520 EELFSVEPLP 1530 PRPSSDQSSS 1540 SSQSQSSYII 1550 RNPQQRRISQ 1560 SQPVRGRDEE 1570 QDDIVSADVE 1580 EVEVVEGVAG 1590 EEDHHDEQEE 1600 HGEENAEAEG 1610 QHDEHDEDGS 1620 DMELDLLAAA 1630 ETESDSESNH 1640 SNQDNASGRR 1650 SVVTAATAGS 1660 EAGASSVPAF 1670 FSEDDSQSND 1680 SSDSDSSSSQ 1690 SDDIEQETFM 1700 LDEPLERTTN 1710 SSHANGAAQA 1720 PRSMQWAVRN 1730 TQHQRAASTA 1740 PSSTSTPAAS 1750 SAGLIYIDPS 1760 NLRRSGTIST 1770 SAAAAAAALE 1780 ASNASSYLTS 1790 ASSLARAYSI 1800 VIRQISDLMG 1810 LIPKYNHLVY 1820 SQIPAAVKLT 1830 YQDAVNLQNY 1840 VEEKLIPTWN 1850 WMVSIMDSTE 1860 AQLRYGSALA 1870 SAGDPGHPNH 1880 PLHASQNSAR 1890 RERMTAREEA 1900 SLRTLEGRRR 1910 ATLLSARQGM 1920 MSARGDFLNY 1930 ALSLMRSHND 1940 EHSDVLPVLD 1950 VCSLKHVAYV 1960 FQALIYWIKA 1970 MNQQTTLDTP 1980 QLERKRTREL 1990 LELGIDNEDS 2000 EHENDDDTNQ 2010 SATLNDKDDD 2020 SLPAETGQNH 2030 PFFRRSDSMT 2040 FLGCIPPNPF 2050 EVPLAEAIPL 2060 ADQPHLLQPN 2070 ARKEDLFGRP 2080 SQGLYSSSAS 2090 SGKCLMEVTV 2100 DRNCLEVLPT 2110 KMSYAANLKN 2120 VMNMQNRQKK 2130 EGEEQPVLPE 2140 ETESSKPGPS 2150 AHDLAAQLKS 2160 SLLAEIGLTE 2170 SEGPPLTSFR 2180 PQCSFMGMVI 2190 SHDMLLGRWR 2200 LSLELFGRVF 2210 MEDVGAEPGS 2220 ILTELGGFEV 2230 KESKFRREME 2240 KLRNQQSRDL 2250 SLEVDRDRDL 2260 LIQQTMRQLN 2270 NHFGRRCATT 2280 PMAVHRVKVT 2290 FKDEPGEGSG 2300 VARSFYTAIA 2310 QAFLSNEKLP 2320 NLECIQNANK 2330 GTHTSLMQRL 2340 RNRGERDRER 2350 EREREMRRSS 2360 GLRAGSRRDR 2370 DRDFRRQLSI 2380 DTRPFRPASE 2390 GNPSDDPEPL 2400 PAHRQALGER 2410 LYPRVQAMQP 2420 AFASKITGML 2430 LELSPAQLLL 2440 LLASEDSLRA 2450 RVDEAMELII 2460 AHGRENGADS 2470 ILDLGLVDSS 2480 EKVQQENRKR 2490 HGSSRSVVDM 2500 DLDDTDDGDD 2510 NAPLFYQPGK 2520 RGFYTPRPGK 2530 NTEARLNCFR 2540 NIGRILGLCL 2550 LQNELCPITL 2560 NRHVIKVLLG 2570 RKVNWHDFAF 2580 FDPVMYESLR 2590 QLILASQSSD 2600 ADAVFSAMDL 2610 AFAIDLCKEE 2620 GGGQVELIPN 2630 GVNIPVTPQN 2640 VYEYVRKYAE 2650 HRMLVVAEQP 2660 LHAMRKGLLD 2670 VLPKNSLEDL 2680 TAEDFRLLVN 2690 GCGEVNVQML 2700 ISFTSFNDES 2710 GENAEKLLQF 2720 KRWFWSIVEK 2730 MSMTERQDLV 2740 YFWTSSPSLP 2750 ASEEGFQPMP 2760 SITIRPPDDQ 2770 HLPTANTCIS 2780 RLYVPLYSSK 2790 QILKQKLLLA IKTKNFGFV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0016020 membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0043130 ubiquitin binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0034450 ubiquitin-ubiquitin ligase 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:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0140861 DNA repair-dependent chromatin remodeling
Biological Process GO:0033696 heterochromatin boundary formation
Biological Process GO:0045879 negative regulation of smoothened signaling pathway
Biological Process GO:0071630 nuclear protein quality control by the ubiquitin-proteasome system
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0042307 positive regulation of protein import into nucleus
Biological Process GO:0050847 progesterone receptor signaling pathway
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:0035519 protein K29-linked ubiquitination
Biological Process GO:0070936 protein K48-linked ubiquitination
Biological Process GO:0000209 protein polyubiquitination

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.