Search Results

Overview

Uniprot IDQ8IWV8
Protein NameE3 ubiquitin-protein ligase UBR2
Gene NameUBR2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1000 LKTFNAVKKMRESSP
361 RLMLSDSKLWKGARS

Function

E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:15548684, PubMed:20835242, PubMed:28392261). Recognizes and binds to proteins bearing specific N-terminal residues (N-degrons) that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:20835242, PubMed:28392261). 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:20835242, PubMed:28392261). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:20835242). In contrast, it strongly binds methylated N-degrons (PubMed:28392261). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (PubMed:20298436). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (By similarity). Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis (By similarity). Plays a role in T-cell receptor signaling by inducing 'Lys-63'-linked ubiquitination of lymphocyte cell-specific kinase LCK (PubMed:38225265). This activity is regulated by DUSP22, which induces 'Lys-48'-linked ubiquitination of UBR2, leading to its proteasomal degradation by SCF E3 ubiquitin-protein ligase complex (PubMed:38225265)

Protein Sequence

10 MASELEPEVQ 20 AIDRSLLECS 30 AEEIAGKWLQ 40 ATDLTREVYQ 50 HLAHYVPKIY 60 CRGPNPFPQK 70 EDMLAQHVLL 80 GPMEWYLCGE 90 DPAFGFPKLE 100 QANKPSHLCG 110 RVFKVGEPTY 120 SCRDCAVDPT 130 CVLCMECFLG 140 SIHRDHRYRM 150 TTSGGGGFCD 160 CGDTEAWKEG 170 PYCQKHELNT 180 SEIEEEEDPL 190 VHLSEDVIAR 200 TYNIFAITFR 210 YAVEILTWEK 220 ESELPADLEM 230 VEKSDTYYCM 240 LFNDEVHTYE 250 QVIYTLQKAV 260 NCTQKEAIGF 270 ATTVDRDGRR 280 SVRYGDFQYC 290 EQAKSVIVRN 300 TSRQTKPLKV 310 QVMHSSIVAH 320 QNFGLKLLSW 330 LGSIIGYSDG 340 LRRILCQVGL 350 QEGPDGENSS 360 LVDRLMLSDS 370 KLWKGARSVY 380 HQLFMSSLLM 390 DLKYKKLFAV 400 RFAKNYQQLQ 410 RDFMEDDHER 420 AVSVTALSVQ 430 FFTAPTLARM 440 LITEENLMSI 450 IIKTFMDHLR 460 HRDAQGRFQF 470 ERYTALQAFK 480 FRRVQSLILD 490 LKYVLISKPT 500 EWSDELRQKF 510 LEGFDAFLEL 520 LKCMQGMDPI 530 TRQVGQHIEM 540 EPEWEAAFTL 550 QMKLTHVISM 560 MQDWCASDEK 570 VLIEAYKKCL 580 AVLMQCHGGY 590 TDGEQPITLS 600 ICGHSVETIR 610 YCVSQEKVSI 620 HLPVSRLLAG 630 LHVLLSKSEV 640 AYKFPELLPL 650 SELSPPMLIE 660 HPLRCLVLCA 670 QVHAGMWRRN 680 GFSLVNQIYY 690 YHNVKCRREM 700 FDKDVVMLQT 710 GVSMMDPNHF 720 LMIMLSRFEL 730 YQIFSTPDYG 740 KRFSSEITHK 750 DVVQQNNTLI 760 EEMLYLIIML 770 VGERFSPGVG 780 QVNATDEIKR 790 EIIHQLSIKP 800 MAHSELVKSL 810 PEDENKETGM 820 ESVIEAVAHF 830 KKPGLTGRGM 840 YELKPECAKE 850 FNLYFYHFSR 860 AEQSKAEEAQ 870 RKLKRQNRED 880 TALPPPVLPP 890 FCPLFASLVN 900 ILQSDVMLCI 910 MGTILQWAVE 920 HNGYAWSESM 930 LQRVLHLIGM 940 ALQEEKQHLE 950 NVTEEHVVTF 960 TFTQKISKPG 970 EAPKNSPSIL 980 AMLETLQNAP 990 YLEVHKDMIR 1000 WILKTFNAVK 1010 KMRESSPTSP 1020 VAETEGTIME 1030 ESSRDKDKAE 1040 RKRKAEIARL 1050 RREKIMAQMS 1060 EMQRHFIDEN 1070 KELFQQTLEL 1080 DASTSAVLDH 1090 SPVASDMTLT 1100 ALGPAQTQVP 1110 EQRQFVTCIL 1120 CQEEQEVKVE 1130 SRAMVLAAFV 1140 QRSTVLSKNR 1150 SKFIQDPEKY 1160 DPLFMHPDLS 1170 CGTHTSSCGH 1180 IMHAHCWQRY 1190 FDSVQAKEQR 1200 RQQRLRLHTS 1210 YDVENGEFLC 1220 PLCECLSNTV 1230 IPLLLPPRNI 1240 FNNRLNFSDQ 1250 PNLTQWIRTI 1260 SQQIKALQFL 1270 RKEESTPNNA 1280 STKNSENVDE 1290 LQLPEGFRPD 1300 FRPKIPYSES 1310 IKEMLTTFGT 1320 ATYKVGLKVH 1330 PNEEDPRVPI 1340 MCWGSCAYTI 1350 QSIERILSDE 1360 DKPLFGPLPC 1370 RLDDCLRSLT 1380 RFAAAHWTVA 1390 SVSVVQGHFC 1400 KLFASLVPND 1410 SHEELPCILD 1420 IDMFHLLVGL 1430 VLAFPALQCQ 1440 DFSGISLGTG 1450 DLHIFHLVTM 1460 AHIIQILLTS 1470 CTEENGMDQE 1480 NPPCEEESAV 1490 LALYKTLHQY 1500 TGSALKEIPS 1510 GWHLWRSVRA 1520 GIMPFLKCSA 1530 LFFHYLNGVP 1540 SPPDIQVPGT 1550 SHFEHLCSYL 1560 SLPNNLICLF 1570 QENSEIMNSL 1580 IESWCRNSEV 1590 KRYLEGERDA 1600 IRYPRESNKL 1610 INLPEDYSSL 1620 INQASNFSCP 1630 KSGGDKSRAP 1640 TLCLVCGSLL 1650 CSQSYCCQTE 1660 LEGEDVGACT 1670 AHTYSCGSGV 1680 GIFLRVRECQ 1690 VLFLAGKTKG 1700 CFYSPPYLDD 1710 YGETDQGLRR 1720 GNPLHLCKER 1730 FKKIQKLWHQ 1740 HSVTEEIGHA 1750 QEANQTLVGI DWQHL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005634 nucleus
Cellular Component GO:0000151 ubiquitin ligase complex
Molecular Function GO:0141053 histone H2A ubiquitin ligase activity
Molecular Function GO:0070728 L-leucine binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0071233 cellular response to L-leucine
Biological Process GO:0031507 heterochromatin formation
Biological Process GO:0007140 male meiotic nuclear division
Biological Process GO:0032007 negative regulation of TOR signaling
Biological Process GO:0050862 positive regulation of T cell receptor signaling pathway
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0007131 reciprocal meiotic recombination
Biological Process GO:0007283 spermatogenesis
Biological Process GO:0010526 transposable element silencing
Biological Process GO:0071596 ubiquitin-dependent protein catabolic process via the N-end rule pathway

Reference

[1] 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.