CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-024778
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase TRIP12 
Protein Synonyms/Alias
 Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12 
Gene Name
 Trip12 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
177ERSAKPTKLASKSATacetylation[1]
1292NRGSQALKFFNTHQLacetylation[1]
1321QWKGGPVKIDPLALVacetylation[1]
1540TSEFINSKLTAKANRubiquitination[2]
1974PPLTIVRKTFESTENubiquitination[2]
Reference
 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [2] 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] 
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 (By similarity). 
Sequence Annotation
 DOMAIN 755 869 WWE.
 DOMAIN 1918 2025 HECT.
 REGION 1529 1603 K-box (By similarity).
 ACT_SITE 1992 1992 Glycyl thioester intermediate (By
 MOD_RES 2 2 N-acetylserine (By similarity).
 MOD_RES 12 12 Phosphoserine (By similarity).
 MOD_RES 77 77 Phosphoserine (By similarity).
 MOD_RES 310 310 Phosphoserine (By similarity).
 MOD_RES 312 312 Phosphoserine (By similarity).
 MOD_RES 975 975 Phosphoserine (By similarity).
 MOD_RES 1024 1024 Phosphoserine (By similarity).
 MOD_RES 1030 1030 Phosphoserine (By similarity).
 MOD_RES 1049 1049 Phosphoserine (By similarity).
 MOD_RES 1063 1063 Phosphoserine (By similarity).
 MOD_RES 1350 1350 Phosphoserine (By similarity).
 MOD_RES 1355 1355 Phosphoserine (By similarity).  
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
 2025 AA 
Protein Sequence
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSA VIVPQPEDPD RANTSERQKT 60
GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPRAFQHIES LSETNKPPSK SKKRHLDQEQ 120
QLKSAQLPST SKAHTRKSVA AGSSRSQKRK RTESSCVKSG SGSESTGAEE RSAKPTKLAS 180
KSATSAKAGC STITDSSSAA STSSSSSAVA SASSTVPAGA RVKQGKDQNK ARRSRSASSP 240
SPRRSSREKE QSKTGGSSKF DWAARFSPKV SLPKTKLSLP GSSKSETSKP GPSGLQAKLA 300
SLRKSTKKRS ESPPAELPSL RRSTRQKTTG SCASTSRRGS GLGKRGAAEA RRQEKMADPE 360
GNQETVNSSA ARTDEAPQGA AASSSVAGAV GMTTSGESES DDSEMGRLQA LLEARGLPPH 420
LFGPLGPRMS QLFHRTIGSG ASSKAQQLLQ GLQASDESQQ LQAVIEMCQL LVMGNEETLG 480
GFPVKSVVPA LITLLQMEHN FDIMNHACRA LTYMMEALPR SSAVVVDAIP VFLEKLQVIQ 540
CIDVAEQALT ALEMLSRRHS KAILQAGGLA DCLLYLEFFS INAQRNALAI AANCCQSITP 600
DEFHFVADSL PLLTQRLTHQ DKKSVESTCL CFARLVDNFQ HEENLLQQVA SKDLLTNVQQ 660
LLVVTPPILS SGMFIMVVRM FSLMCSNCPT LAVQLMKQNI AETLHFLLCG ASNGSCQEQI 720
DLVPRSPQEL YELTSLICEL MPCLPKEGIF AVDTMLKKGN AQNTDGAIWQ WRDDRGLWHP 780
YNRIDSRIIE AAHQVGEDEI SLSTLGRVYT IDFNSMQQIN EDTGTARAIQ RKPNPLANTN 840
TSGYSDLKKD DARAQLMKED PELAKSFIKT LFGVLYEVYS SSAGPAVRHK CLRAILRIIY 900
FADAELLKDV LKNHAVSSHI ASMLSSQDLK IVVGALQMAE ILMQKLPDIF SVYFRREGVM 960
HQVKHLAESE SLLTSPPKAC TNGSGSLGST TPASSGTATA ATNASADLGS PSLQHSRDDS 1020
LDLSPQGRLS DVLKRKRLPK RGPRRPKYSP PRDDDKVDNQ AKSPTTTQSP KSSFLASLNP 1080
KTWGRLSAQS NSNNIEPART AGVSGLARAA SKDTISNNRE KIKGWIKEQA HKFVERYFSS 1140
ENMDGSNPAL NVLQRLCAAT EQLNLQVDGG AECLVEIRSI VSESDVSSFE IQHSGFVKQL 1200
LLYLTSKSEK DAVSREIRLK RFLHVFFSSP LPGEEPVGRV EPVGHAPLLA LVHKMNNCLS 1260
QMEQFPVKVH DFPSGNGSGG SFSLNRGSQA LKFFNTHQLK CQLQRHPDCA NVKQWKGGPV 1320
KIDPLALVQA IERYLVVRGY GRVREDDEDS DDDGSDEEID ESLAAQFLNS GNVRHRLQFY 1380
IGEHLLPYNM TVYQAVRQFS VQAEDEREST DDESNPLGRA GIWTKTHTIW YKPVREDEES 1440
SKDCVGGKRG RAQTAPTKTS PRNAKKHDEL WHDGVCPSVA NPLEVYLIPT PPENITFEDP 1500
SLDVILLLRV LHAISRYWYY LYDNAMCKEI IPTSEFINSK LTAKANRQLQ DPLVIMTGNI 1560
PTWLTELGKT CPFFFPFDTR QMLFYVTAFD RDRAMQRLLD TNPEINQSDS QDSRVAPRLD 1620
RKKRTVNREE LLKQAESVMQ DLGSSRAMLE IQYENEVGTG LGPTLEFYAL VSQELQRADL 1680
GLWRGEEVTL SNPKGSQEGT KYIQNLQGLF ALPFGRTAKP AHIAKVKMKF RFLGKLMAKA 1740
IMDFRLVDLP LGLPFYKWML RQETSLTSHD LFDIDPVVAR SVYHLEDIVR QKKRLEQDKS 1800
QTKESLQYAL ETLTMNGCSV EDLGLDFTLP GFPNIELKKG GKDIPVTIHN LEEYLRLVIF 1860
WALNEGVCRQ FDSFRDGFES VFPLSHLQYF YPEELDQLLC GSKADTWDAK TLMECCRPDH 1920
GYTHDSRAVK FLFEILSSFD NEQQRLFLQF VTGSPRLPVG GFRSLNPPLT IVRKTFESTE 1980
NPDDFLPSVM TCVNYLKLPD YSSIEIMRDK LLIAAREGQQ SFHLS 2025 
Gene Ontology
 GO:0005737; C:cytoplasm; IBA:RefGenome.
 GO:0005654; C:nucleoplasm; ISS:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; ISS: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; ISS:UniProtKB.
 GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; ISS:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
 GO:0006974; P:response to DNA damage stimulus; ISS:UniProtKB. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR000569; HECT.
 IPR004170; WWE-dom. 
Pfam
 PF00632; HECT
 PF02825; WWE 
SMART
 SM00119; HECTc 
PROSITE
 PS50237; HECT
 PS50918; WWE 
PRINTS