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Overview

Uniprot ID	Q14669
Protein Name	E3 ubiquitin-protein ligase TRIP12
Gene Name	TRIP12
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
132	TNSPSSAKKPKALQH

Function

E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692, PubMed:40419785). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key 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). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744)

Protein Sequence

10 MSNRPNNNPG 20 GSLRRSQRNT 30 AGAQPQDDSI 40 GGRSHLGQAK 50 HKGYSPPESR 60 KSNSKAPKVQ 70 SNTTSELSRG 80 HLSKRSCSSS 90 SAVIVPQPED 100 PDRANTSERQ 110 KTGQVPKKDN 120 SRGVKRSASP 130 DYNRTNSPSS 140 AKKPKALQHT 150 ESPSETNKPH 160 SKSKKRHLDQ 170 EQQLKSAQSP 180 STSKAHTRKS 190 GATGGSRSQK 200 RKRTESSCVK 210 SGSGSESTGA 220 EERSAKPTKL 230 ASKSATSAKA 240 GCSTITDSSS 250 AASTSSSSSA 260 VASASSTVPP 270 GARVKQGKDQ 280 NKARRSRSAS 290 SPSPRRSSRE 300 KEQSKTGGSS 310 KFDWAARFSP 320 KVSLPKTKLS 330 LPGSSKSETS 340 KPGPSGLQAK 350 LASLRKSTKK 360 RSESPPAELP 370 SLRRSTRQKT 380 TGSCASTSRR 390 GSGLGKRGAA 400 EARRQEKMAD 410 PESNQEAVNS 420 SAARTDEAPQ 430 GAAASSSVAG 440 AVGMTTSGES 450 ESDDSEMGRL 460 QALLEARGLP 470 PHLFGPLGPR 480 MSQLFHRTIG 490 SGASSKAQQL 500 LQGLQASDES 510 QQLQAVIEMC 520 QLLVMGNEET 530 LGGFPVKSVV 540 PALITLLQME 550 HNFDIMNHAC 560 RALTYMMEAL 570 PRSSAVVVDA 580 IPVFLEKLQV 590 IQCIDVAEQA 600 LTALEMLSRR 610 HSKAILQAGG 620 LADCLLYLEF 630 FSINAQRNAL 640 AIAANCCQSI 650 TPDEFHFVAD 660 SLPLLTQRLT 670 HQDKKSVEST 680 CLCFARLVDN 690 FQHEENLLQQ 700 VASKDLLTNV 710 QQLLVVTPPI 720 LSSGMFIMVV 730 RMFSLMCSNC 740 PTLAVQLMKQ 750 NIAETLHFLL 760 CGASNGSCQE 770 QIDLVPRSPQ 780 ELYELTSLIC 790 ELMPCLPKEG 800 IFAVDTMLKK 810 GNAQNTDGAI 820 WQWRDDRGLW 830 HPYNRIDSRI 840 IEAAHQVGED 850 EISLSTLGRV 860 YTIDFNSMQQ 870 INEDTGTARA 880 IQRKPNPLAN 890 SNTSGYSESK 900 KDDARAQLMK 910 EDPELAKSFI 920 KTLFGVLYEV 930 YSSSAGPAVR 940 HKCLRAILRI 950 IYFADAELLK 960 DVLKNHAVSS 970 HIASMLSSQD 980 LKIVVGALQM 990 AEILMQKLPD 1000 IFSVYFRREG 1010 VMHQVKHLAE 1020 SESLLTSPPK 1030 ACTNGSGSMG 1040 STTSVSSGTA 1050 TAATHAAADL 1060 GSPSLQHSRD 1070 DSLDLSPQGR 1080 LSDVLKRKRL 1090 PKRGPRRPKY 1100 SPPRDDDKVD 1110 NQAKSPTTTQ 1120 SPKSSFLASL 1130 NPKTWGRLST 1140 QSNSNNIEPA 1150 RTAGGSGLAR 1160 AASKDTISNN 1170 REKIKGWIKE 1180 QAHKFVERYF 1190 SSENMDGSNP 1200 ALNVLQRLCA 1210 ATEQLNLQVD 1220 GGAECLVEIR 1230 SIVSESDVSS 1240 FEIQHSGFVK 1250 QLLLYLTSKS 1260 EKDAVSREIR 1270 LKRFLHVFFS 1280 SPLPGEEPIG 1290 RVEPVGNAPL 1300 LALVHKMNNC 1310 LSQMEQFPVK 1320 VHDFPSGNGT 1330 GGSFSLNRGS 1340 QALKFFNTHQ 1350 LKCQLQRHPD 1360 CANVKQWKGG 1370 PVKIDPLALV 1380 QAIERYLVVR 1390 GYGRVREDDE 1400 DSDDDGSDEE 1410 IDESLAAQFL 1420 NSGNVRHRLQ 1430 FYIGEHLLPY 1440 NMTVYQAVRQ 1450 FSIQAEDERE 1460 STDDESNPLG 1470 RAGIWTKTHT 1480 IWYKPVREDE 1490 ESNKDCVGGK 1500 RGRAQTAPTK 1510 TSPRNAKKHD 1520 ELWHDGVCPS 1530 VSNPLEVYLI 1540 PTPPENITFE 1550 DPSLDVILLL 1560 RVLHAISRYW 1570 YYLYDNAMCK 1580 EIIPTSEFIN 1590 SKLTAKANRQ 1600 LQDPLVIMTG 1610 NIPTWLTELG 1620 KTCPFFFPFD 1630 TRQMLFYVTA 1640 FDRDRAMQRL 1650 LDTNPEINQS 1660 DSQDSRVAPR 1670 LDRKKRTVNR 1680 EELLKQAESV 1690 MQDLGSSRAM 1700 LEIQYENEVG 1710 TGLGPTLEFY 1720 ALVSQELQRA 1730 DLGLWRGEEV 1740 TLSNPKGSQE 1750 GTKYIQNLQG 1760 LFALPFGRTA 1770 KPAHIAKVKM 1780 KFRFLGKLMA 1790 KAIMDFRLVD 1800 LPLGLPFYKW 1810 MLRQETSLTS 1820 HDLFDIDPVV 1830 ARSVYHLEDI 1840 VRQKKRLEQD 1850 KSQTKESLQY 1860 ALETLTMNGC 1870 SVEDLGLDFT 1880 LPGFPNIELK 1890 KGGKDIPVTI 1900 HNLEEYLRLV 1910 IFWALNEGVS 1920 RQFDSFRDGF 1930 ESVFPLSHLQ 1940 YFYPEELDQL 1950 LCGSKADTWD 1960 AKTLMECCRP 1970 DHGYTHDSRA 1980 VKFLFEILSS 1990 FDNEQQRLFL 2000 QFVTGSPRLP 2010 VGGFRSLNPP 2020 LTIVRKTFES 2030 TENPDDFLPS 2040 VMTCVNYLKL 2050 PDYSSIEIMR 2060 EKLLIAAREG QQSFHLS

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0016607	nuclear speck
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0046966	nuclear thyroid hormone receptor binding
Molecular Function	GO:0061630	ubiquitin protein ligase activity
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:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process	GO:0000209	protein polyubiquitination
Biological Process	GO:0045995	regulation of embryonic development
Biological Process	GO:0006511	ubiquitin-dependent protein catabolic process

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.