ID   TRIPC_DANRE             Reviewed;        2026 AA.
AC   F1RCR6; A3KPN5;
DT   03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT   03-MAY-2011, sequence version 1.
DT   03-AUG-2022, entry version 67.
DE   RecName: Full=E3 ubiquitin-protein ligase TRIP12;
DE            EC=2.3.2.26;
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; Synonyms=si:ch211-272f3.4;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
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. {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   -!- 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; BX255887; CAM56489.1; -; Genomic_DNA.
DR   EMBL; CU928079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; F1RCR6; -.
DR   SMR; F1RCR6; -.
DR   STRING; 7955.ENSDARP00000082000; -.
DR   PaxDb; F1RCR6; -.
DR   Ensembl; ENSDART00000145863; ENSDARP00000112916; ENSDARG00000061397.
DR   ZFIN; ZDB-GENE-041111-262; trip12.
DR   eggNOG; KOG0168; Eukaryota.
DR   eggNOG; KOG0170; Eukaryota.
DR   GeneTree; ENSGT00940000156517; -.
DR   HOGENOM; CLU_000366_2_0_1; -.
DR   InParanoid; F1RCR6; -.
DR   OMA; PLECADE; -.
DR   Reactome; R-DRE-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:F1RCR6; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 18.
DR   Bgee; ENSDARG00000061397; Expressed in retina and 20 other tissues.
DR   ExpressionAtlas; F1RCR6; baseline.
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   3: Inferred from homology;
KW   DNA damage; DNA repair; Nucleus; Phosphoprotein; Reference proteome;
KW   Transferase; Ubl conjugation pathway.
FT   CHAIN           1..2026
FT                   /note="E3 ubiquitin-protein ligase TRIP12"
FT                   /id="PRO_0000419691"
FT   DOMAIN          789..876
FT                   /note="WWE"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT   DOMAIN          1919..2026
FT                   /note="HECT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   REGION          1..437
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1008..1123
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1441..1470
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1530..1604
FT                   /note="K-box"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1..42
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        58..83
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        94..108
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        147..190
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        212..251
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        350..371
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        377..392
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        393..432
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1008..1029
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1052..1066
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1067..1107
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1993
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
SQ   SEQUENCE   2026 AA;  223044 MW;  D147E876B6C67A1E CRC64;
     MSNRPNSNPG GSLRRSQRNT AAAQPIDHTL AGRNSLSLSV GSLSIPDPDL EAAGTSGQQG
     RREGSSTRAL KRSSVSEPNI TFSPSPAKRP KVVSSHFSDS SASGPSAPAI SPEVTEPRKA
     PASVSTKSKK RRLAAEPAPA RALSKKSSSY PGPSGASSTP SQKRKKADAT LLSSSSSSSL
     PSSSSAAGPL PPRSEASRAA KPTKLASKSA ASAKAGCSTV TDSSSSSASS SSSSSSSSSA
     ATGTNSCAPQ GARLKQGKDQ SKARRSRSAS SPSPRRSSRD KEQSKAAGSS KFDWASRFNS
     KVNLPKPKLS LPGSAKAETS SKPGPSGLQA KLASLRKSTK KRSESPPAEL PSCRRSTRQK
     TTGSCASTSR RGSGLGKRGA AEARRQEKMA DSDNNQDGAN SSAARTEETP QGASASSSVA
     GAVGMTTSGE SESDDSEMGR LQALLEARGL PPHLFGPFGP RMSQLFHRTI GSGASSKAQQ
     LLQGLQATGD ESQQLQAAIE MCQLLVMGNE ETLGGFPVKS VVPALITLLQ MEHNFDIMNH
     ASRALTYMME ALPRSSAVVV DAIPVFLEKL QVIQFIDVAE QALTALEMLS RRHSKAILQA
     GGLADCLLYL EFFSINAQRN ALAIAANCCQ SITPDEFHFV ADSLPLLTQR LTHQDKKSVE
     STCLCFARLV DNFQHEENLL QQVASRDLLT NIQQLLVLTP PVLSSGMFIM VVRMFSLMCS
     NCPCLAVQLM KQNIAETLRF LLCGASNGSC QEQIDLVPRS PQELYELTSL ICELMPCLPR
     EGIFAVDAML KKGSAQTTEG AIWQWRDDRG LWHPYNRIDS RIIEQINEDT GTARAIQRKP
     NPLANPNTGG HLEVRREDAR AQLMKEDPEL AKCFIKTLFG VLYEVYSSSA GPAVRHKCLR
     AILRIIYFAD AELLKDVLRN HAVSSHIASM LSSQDLKIVV GSLQMAEILM QKLPDVFSVY
     FRREGVMHQV KNLAESEVFL TSPPKACTSG TASLCTTTIT TATTTAASNV TPDLGSPSFQ
     HSMDDSLDLS PQGRLSDVLK RKRLPKRGPR RPKYSPPRDD DKVDNQAKSP TTTQSPKSSF
     LASLNPKTWG KLGTQANSAN SEPSRTAGVS GLARVPPKDS VSNNRDKIKA WIKEQASKFV
     ERYFNSESVD GSNPALNVLQ RLCTATEQLN LQMDSGVECL EEISSIVSES DVSSFEIQHS
     GLVKQLLLYL TSNSERDTIS RDERIKRFLH VFFGCPIPGQ EPPGRLDPTE NGPLLALVHK
     MNNCLSQMEQ FPVKVHDFPS GNGNGSRGSQ ALKFFNTHQL KCQLQRHPDC TNVKQWKGGP
     VKIDPLALVQ AIERYLVVRG YGRIREEDED SDDDGSDDEI DESLAAQFLN SGSVRHRLQF
     YIGEHLLPYN MTVYQAVRQF SLQAEEERES TDDEANPLGR AGIWTKTHTV WYKPVREDEE
     GCKDAVGGKR GRAQTAPTKT SPRNAKKQDE LWHEGVCPSV ANPLETYLIC DPPEGITFDD
     PSMEVILLLR VLHSISRYWF YLYDNAACKE IIPTGEFINS KLTAKANRQL QDPLVIMTGN
     IPTWLTELGK TCPFFFPFDT RQMLFYVTAF DRDRAMQRLL DTNPEINQSD SQDSRVAPRL
     DRKKRTINRD ELLKQAESVM QDLGSSRAML EIQYENEVGT GLGPTQEFYA LVSQELQRAD
     LGLWRGEEVT LSNPKGSQEG TKYMFSSRGL FAVPFGRTTK PAHIAKIKMK FRFLGKLMAK
     AIMDFRLLDL PLGLPFYKWM LRHESSISSH DLVNIDPGVA KSIQHLEDII RQKKRIEQDR
     SHTRETLQQA LESLNMNGCS VEDLGLDFTL PGFPNIELKK GGKDVPVTIH NLEDYLRLVV
     YWTLNEGVLR QFESFREGFE SVFPLHHLQY FYPEELDQLL CGSKSESWDV KTLMECCRPD
     HGYTHDSRAV RFLFEVLSSF DAEQQRLFLQ FVTGSPRLPV GGFRSLNPPL TIVRKTFEST
     ENPDDFLPSV MTCVNYLKLP DYSSIEIMRE KLLIAAREGQ QSFHLS