CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012359
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase TRIP12 
Protein Synonyms/Alias
 E3 ubiquitin-protein ligase for Arf; ULF; Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12 
Gene Name
 TRIP12 
Gene Synonyms/Alias
 KIAA0045; ULF 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
298GPSGLQAKLASLRKSubiquitination[1]
355AEARRQEKMADPESNubiquitination[2, 3, 4]
617RLTHQDKKSVESTCLubiquitination[5]
751FAVDTMLKKGNAQNTubiquitination[3]
752AVDTMLKKGNAQNTDubiquitination[3]
799TARAIQRKPNPLANSubiquitination[2, 3, 5]
1001GRLSDVLKRKRLPKRubiquitination[2, 3, 5]
1038PTTTQSPKSSFLASLubiquitination[1, 2, 3, 4, 5, 6, 7, 8]
1048FLASLNPKTWGRLSTubiquitination[1, 2, 3, 4, 5, 6, 7, 8]
1221PLLALVHKMNNCLSQubiquitination[3]
1259NRGSQALKFFNTHQLubiquitination[1, 2, 3, 4, 5]
1267FFNTHQLKCQLQRHPubiquitination[3]
1280HPDCANVKQWKGGPVubiquitination[3, 5]
1283CANVKQWKGGPVKIDubiquitination[3]
1288QWKGGPVKIDPLALVacetylation[9]
1288QWKGGPVKIDPLALVubiquitination[1, 2, 3, 4, 5, 10]
1425RAQTAPTKTSPRNAKubiquitination[3, 5]
1507TSEFINSKLTAKANRubiquitination[3, 5]
1600VNREELLKQAESVMQubiquitination[2, 3, 5]
1661EVTLSNPKGSQEGTKubiquitination[2, 3, 4, 5, 6]
1668KGSQEGTKYIQNLQGubiquitination[4, 5, 6]
1702MKFRFLGKLMAKAIMubiquitination[3, 5]
1941PPLTIVRKTFESTENubiquitination[3]
1977SIEIMREKLLIAAREubiquitination[3]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [8] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. 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. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. 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. 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. 
Sequence Annotation
 DOMAIN 749 836 WWE.
 DOMAIN 1885 1992 HECT.
 REGION 1496 1570 K-box.
 ACT_SITE 1959 1959 Glycyl thioester intermediate (Probable).
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 12 12 Phosphoserine.
 MOD_RES 77 77 Phosphoserine.
 MOD_RES 310 310 Phosphoserine.
 MOD_RES 312 312 Phosphoserine.
 MOD_RES 942 942 Phosphoserine.
 MOD_RES 991 991 Phosphoserine.
 MOD_RES 997 997 Phosphoserine.
 MOD_RES 1016 1016 Phosphoserine (By similarity).
 MOD_RES 1030 1030 Phosphoserine.
 MOD_RES 1317 1317 Phosphoserine.
 MOD_RES 1322 1322 Phosphoserine.  
Keyword
 Acetylation; Alternative splicing; Complete proteome; DNA damage; DNA repair; Ligase; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1992 AA 
Protein Sequence
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSA VIVPQPEDPD RANTSERQKT 60
GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPKALQHTES PSETNKPHSK SKKRHLDQEQ 120
QLKSAQSPST SKAHTRKSGA TGGSRSQKRK RTESSCVKSG SGSESTGAEE RSAKPTKLAS 180
KSATSAKAGC STITDSSSAA STSSSSSAVA SASSTVPPGA RVKQGKDQNK ARRSRSASSP 240
SPRRSSREKE QSKTGGSSKF DWAARFSPKV SLPKTKLSLP GSSKSETSKP GPSGLQAKLA 300
SLRKSTKKRS ESPPAELPSL RRSTRQKTTG SCASTSRRGS GLGKRGAAEA RRQEKMADPE 360
SNQEAVNSSA ARTDEAPQGA AGAVGMTTSG ESESDDSEMG RLQALLEARG LPPHLFGPLG 420
PRMSQLFHRT IGSGASSKAQ QLLQGLQASD ESQQLQAVIE MCQLLVMGNE ETLGGFPVKS 480
VVPALITLLQ MEHNFDIMNH ACRALTYMME ALPRSSAVVV DAIPVFLEKL QVIQCIDVAE 540
QALTALEMLS RRHSKAILQA GGLADCLLYL EFFSINAQRN ALAIAANCCQ SITPDEFHFV 600
ADSLPLLTQR LTHQDKKSVE STCLCFARLV DNFQHEENLL QQVASKDLLT NVQQLLVVTP 660
PILSSGMFIM VVRMFSLMCS NCPTLAVQLM KQNIAETLHF LLCGASNGSC QEQIDLVPRS 720
PQELYELTSL ICELMPCLPK EGIFAVDTML KKGNAQNTDG AIWQWRDDRG LWHPYNRIDS 780
RIIEQINEDT GTARAIQRKP NPLANSNTSG YSESKKDDAR AQLMKEDPEL AKSFIKTLFG 840
VLYEVYSSSA GPAVRHKCLR AILRIIYFAD AELLKDVLKN HAVSSHIASM LSSQDLKIVV 900
GALQMAEILM QKLPDIFSVY FRREGVMHQV KHLAESESLL TSPPKACTNG SGSMGSTTSV 960
SSGTATAATH AAADLGSPSL QHSRDDSLDL SPQGRLSDVL KRKRLPKRGP RRPKYSPPRD 1020
DDKVDNQAKS PTTTQSPKSS FLASLNPKTW GRLSTQSNSN NIEPARTAGG SGLARAASKD 1080
TISNNREKIK GWIKEQAHKF VERYFSSENM DGSNPALNVL QRLCAATEQL NLQVDGGAEC 1140
LVEIRSIVSE SDVSSFEIQH SGFVKQLLLY LTSKSEKDAV SREIRLKRFL HVFFSSPLPG 1200
EEPIGRVEPV GNAPLLALVH KMNNCLSQME QFPVKVHDFP SGNGTGGSFS LNRGSQALKF 1260
FNTHQLKCQL QRHPDCANVK QWKGGPVKID PLALVQAIER YLVVRGYGRV REDDEDSDDD 1320
GSDEEIDESL AAQFLNSGNV RHRLQFYIGE HLLPYNMTVY QAVRQFSIQA EDERESTDDE 1380
SNPLGRAGIW TKTHTIWYKP VREDEESNKD CVGGKRGRAQ TAPTKTSPRN AKKHDELWHD 1440
GVCPSVSNPL EVYLIPTPPE NITFEDPSLD VILLLRVLHA ISRYWYYLYD NAMCKEIIPT 1500
SEFINSKLTA KANRQLQDPL VIMTGNIPTW LTELGKTCPF FFPFDTRQML FYVTAFDRDR 1560
AMQRLLDTNP EINQSDSQDS RVAPRLDRKK RTVNREELLK QAESVMQDLG SSRAMLEIQY 1620
ENEVGTGLGP TLEFYALVSQ ELQRADLGLW RGEEVTLSNP KGSQEGTKYI QNLQGLFALP 1680
FGRTAKPAHI AKVKMKFRFL GKLMAKAIMD FRLVDLPLGL PFYKWMLRQE TSLTSHDLFD 1740
IDPVVARSVY HLEDIVRQKK RLEQDKSQTK ESLQYALETL TMNGCSVEDL GLDFTLPGFP 1800
NIELKKGGKD IPVTIHNLEE YLRLVIFWAL NEGVSRQFDS FRDGFESVFP LSHLQYFYPE 1860
ELDQLLCGSK ADTWDAKTLM ECCRPDHGYT HDSRAVKFLF EILSSFDNEQ QRLFLQFVTG 1920
SPRLPVGGFR SLNPPLTIVR KTFESTENPD DFLPSVMTCV NYLKLPDYSS IEIMREKLLI 1980
AAREGQQSFH LS 1992 
Gene Ontology
 GO:0005737; C:cytoplasm; IBA:RefGenome.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0046966; F:thyroid hormone receptor binding; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0009790; P:embryo development; ISS:UniProtKB.
 GO:2000780; P:negative regulation of double-strand break repair; IMP:UniProtKB.
 GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; IMP:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0006974; P:response to DNA damage stimulus; IMP:UniProtKB. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR000569; HECT.
 IPR004170; WWE-dom. 
Pfam
 PF00632; HECT 
SMART
 SM00119; HECTc 
PROSITE
 PS50237; HECT
 PS50918; WWE 
PRINTS