TRIPC_BOVIN
ID TRIPC_BOVIN Reviewed; 1992 AA.
AC E1B7Q7; Q0P5M6;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=E3 ubiquitin-protein ligase TRIP12;
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:Q14669};
DE AltName: Full=HECT-type E3 ubiquitin transferase TRIP12;
DE AltName: Full=Thyroid receptor-interacting protein 12;
DE Short=TR-interacting protein 12;
DE Short=TRIP-12;
GN Name=TRIP12;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 878-1992.
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase involved in ubiquitin fusion
CC degradation (UFD) pathway and regulation of DNA repair. Part of the
CC ubiquitin fusion degradation (UFD) pathway, a process that mediates
CC ubiquitination of protein at their N-terminus, regardless of the
CC presence of lysine residues in target proteins. Acts as a key regulator
CC of DNA damage response by acting as a suppressor of RNF168, an E3
CC ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked
CC histone H2A and H2AX at DNA damage sites, thereby acting as a guard
CC against excessive spreading of ubiquitinated chromatin at damaged
CC chromosomes. In normal cells, mediates ubiquitination and degradation
CC of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor
CC required for p53/TP53 activation under oncogenic stress. In cancer
CC cells, however, isoform p19ARF/ARF and TRIP12 are located in different
CC cell compartments, preventing isoform p19ARF/ARF ubiquitination and
CC degradation. Does not mediate ubiquitination of isoform p16-INK4a of
CC CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to
CC their degradation. Ubiquitination and degradation of target proteins is
CC regulated by interaction with proteins such as MYC, TRADD or SMARCC1,
CC which disrupt the interaction between TRIP12 and target proteins.
CC Mediates ubiquitination of ASXL1: following binding to N(6)-
CC methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12,
CC leading to its degradation and subsequent inactivation of the PR-DUB
CC complex. {ECO:0000250|UniProtKB:Q14669}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000250|UniProtKB:Q14669};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q14669}.
CC -!- SUBUNIT: Interacts with MYC; leading to disrupt interaction with
CC isoform p19ARF/ARF of CDKN2A. Interacts with TRADD; leading to disrupt
CC interaction with isoform p19ARF/ARF of CDKN2A. Interacts with SMARCC1;
CC leading to disrupt interaction with SMARCE1.
CC {ECO:0000250|UniProtKB:Q14669}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q14669}.
CC -!- SIMILARITY: Belongs to the UPL family. K-HECT subfamily. {ECO:0000305}.
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DR EMBL; DAAA02006173; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02006174; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02006175; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119851; AAI19852.1; -; mRNA.
DR RefSeq; NP_001178132.1; NM_001191203.1.
DR AlphaFoldDB; E1B7Q7; -.
DR SMR; E1B7Q7; -.
DR STRING; 9913.ENSBTAP00000037967; -.
DR iPTMnet; E1B7Q7; -.
DR PaxDb; E1B7Q7; -.
DR PRIDE; E1B7Q7; -.
DR Ensembl; ENSBTAT00000038151; ENSBTAP00000037967; ENSBTAG00000021653.
DR GeneID; 514387; -.
DR KEGG; bta:514387; -.
DR CTD; 9320; -.
DR VEuPathDB; HostDB:ENSBTAG00000021653; -.
DR VGNC; VGNC:36358; TRIP12.
DR eggNOG; KOG0168; Eukaryota.
DR eggNOG; KOG0170; Eukaryota.
DR GeneTree; ENSGT00940000156517; -.
DR HOGENOM; CLU_000366_2_0_1; -.
DR InParanoid; E1B7Q7; -.
DR OMA; PLECADE; -.
DR OrthoDB; 34110at2759; -.
DR TreeFam; TF323674; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000021653; Expressed in spermatocyte and 108 other tissues.
DR ExpressionAtlas; E1B7Q7; baseline and differential.
DR GO; GO:0016607; C:nuclear speck; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:2000780; P:negative regulation of double-strand break repair; ISS:UniProtKB.
DR GO; GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:2000779; P:regulation of double-strand break repair; IBA:GO_Central.
DR GO; GO:0045995; P:regulation of embryonic development; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR045322; HECTD1/TRIP12-like.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR037197; WWE_dom_sf.
DR PANTHER; PTHR45670; PTHR45670; 1.
DR Pfam; PF00632; HECT; 1.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50918; WWE; 1.
PE 2: Evidence at transcript level;
KW Acetylation; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT CHAIN 2..1992
FT /note="E3 ubiquitin-protein ligase TRIP12"
FT /id="PRO_0000419688"
FT DOMAIN 749..836
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 1885..1992
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 1..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 938..1044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1407..1434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1496..1570
FT /note="K-box"
FT /evidence="ECO:0000250"
FT REGION 1568..1587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..73
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..336
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..359
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 941..987
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1013..1027
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1028..1044
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1959
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 942
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 997
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LP64"
FT MOD_RES 1030
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 1317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 1322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14669"
FT MOD_RES 1329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 1376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LP64"
FT MOD_RES 1377
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F1LP64"
FT MOD_RES 1425
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 1427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
SQ SEQUENCE 1992 AA; 220390 MW; FA16BFF3BDB01BFA CRC64;
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSV VIVPQPEDPD RANTSEKQKT
GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPKALQHTES PSETSKPHSK SKKRHLDQEP
QLKSAPSPST SKAHTRKSGA AAGSRSQKRK RTESSCIKSA SVSEATGAEE RSAKPTKLAS
KSAASAKAGC STITDSSSAA STSSSSSAVA SASSAVPPGA RVKQGKDQNK ARRSRSASSP
SPRRSSREKE QSKTGGSSKF DWAARFSPKV SLPKTKLSLP GSSKSETSKP GPSGLQAKLA
SLRKSTKKRS ESPPAELPSL RRSTRQKTTG SCASASRRGS GLGKRGAAEA RRQEKMADPE
GNQETVNSSA ARTDETPQGA AGAVGMTTSG ESESDDSEMG RLQALLEARG LPPHLFGPLG
PRMSQLFHRT IGSGASSKAQ QLLQGLQASD ESQQLQAVIE MCQLLVMGNE ETLGGFPVKS
VVPALITLLQ MEHNFDIMNH ACRALTYMME ALPRSSAVVV DAIPVFLEKL QVIQCIDVAE
QALTALEMLS RRHSKAILQA GGLADCLLYL EFFSINAQRN ALAIAANCCQ SITPDEFHFV
ADSLPLLTQR LTHQDKKSVE STCLCFARLV DNFQHEENLL QQVASKDLLT NVQQLLVVTP
PILSSGMFIM VVRMFSLMCS NCPTLAVQLM KQNIAETLHF LLCGASNGSC QEQIDLVPRS
PQELYELTSL ICELMPCLPK EGIFAVDTML KKGNAQNTDG AIWQWRDDRG LWHPYNRIDS
RIIEQINEDT GTARAIQRKP NPLANTNTSG YSELKKDDAR AQLMKEDPEL AKSFIKTLFG
VLYEVYSSSA GPAVRHKCLR AILRIIYFAD AELLKDVLKN HAVSSHIASM LSSQDLKIVV
GALQMAEILM QKLPDIFSVY FRREGVMHQV KHLAESESLL TSPPKACTNG SGSLGSTPSV
NSGTATAATN ASADLGSPSL QHSRDDSLDL SPQGRLSDVL KRKRLPKRGS RRPKYSPPRD
DDKVDNQAKS PTTTQSPKSS FLASLNPKTW GRLSAQSNSN NIEPARTAGV SGLARAASKD
TISNNREKIK GWIKEQAHKF VERYFSSENM DGSNPALNVL QRLCAATEQL NLQVDGGAEC
LVEIRSIVSE SDVSSFEIQH SGFVKQLLLY LTSKSEKDAV SREIRLKRFL HVFFSSPLPG
EEPIERVEPV GNAPLLALVH KMNNCLSQME QFPVKVHDFP SGNGTGGSFS LNRGSQALKF
FNTHQLKCQL QRHPDCANVK QWKGGPVKID PLALVQAIER YLVVRGYGRV REDDEDSDDD
GSDEEIDESL AAQFLNSGNV RHRLQFYIGE HLLPYNMTVY QAVRQFSIQA EDERESTDDE
SNPLGRAGIW TKTHTIWYKP VREDEESNKD CVGGKRGRAQ TAPTKTSPRN AKKHDELWND
GVCPSVSNPL EVYLIPTAPE NITFEDPSLD VILLLRVLHA VSRYWYYLYD NAMCKEIIPT
SEFINSKLTA KANRQLQDPL VIMTGNIPTW LTELGKTCPF FFPFDTRQML FYVTAFDRDR
AMQRLLDTNP EINQSDSQDS RVAPRLDRKK RTVNREELLK QAESVMQDLG SSRAMLEIQY
ENEVGTGLGP TLEFYALVSQ ELQRADLGLW RGEEVTLSNP KGSQEGTKYI QNLQGLFALP
FGRTAKPAHI AKVKMKFRFL GKLMAKAIMD FRLVDLPLGL PFYKWMLRQE TSLTSHDLFD
IDPVVARSVY HLEDIVRQKK RLEQDKSQTK ESLQYALETL TMNGCSVEDL GLDFTLPGFP
NIELKKGGKD IPVTIHNLEE YLRLVIFWAL NEGVSRQFDS FRDGFESVFP LSHLQYFYPE
ELDQLLCGSK ADTWDAKTLM ECCRPDHGYT HDSRAVKFLF EILSSFDNEQ QRLFLQFVTG
SPRLPVGGFR SLNPPLTIVR KTFESTENPD DFLPSVMTCV NYLKLPDYSS LEIMREKLLM
AAREGQQSFH LS
