TRIPC_HUMAN
ID TRIPC_HUMAN Reviewed; 1992 AA.
AC Q14669; D4HL82; Q14CA3; Q14CF1; Q15644; Q53R87; Q53TE7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=E3 ubiquitin-protein ligase TRIP12;
DE EC=2.3.2.26 {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:30982744};
DE AltName: Full=E3 ubiquitin-protein ligase for Arf;
DE Short=ULF;
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=KIAA0045, ULF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH MYC AND CDKN2A, AND MUTAGENESIS OF CYS-1959.
RX PubMed=20208519; DOI=10.1038/nature08820;
RA Chen D., Shan J., Zhu W.G., Qin J., Gu W.;
RT "Transcription-independent ARF regulation in oncogenic stress-mediated p53
RT responses.";
RL Nature 464:624-627(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1801-1992.
RX PubMed=7776974; DOI=10.1210/mend.9.2.7776974;
RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.;
RT "Two classes of proteins dependent on either the presence or absence of
RT thyroid hormone for interaction with the thyroid hormone receptor.";
RL Mol. Endocrinol. 9:243-254(1995).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP FUNCTION.
RX PubMed=18627766; DOI=10.1016/j.bbrc.2008.07.019;
RA Park Y., Yoon S.K., Yoon J.B.;
RT "TRIP12 functions as an E3 ubiquitin ligase of APP-BP1.";
RL Biochem. Biophys. Res. Commun. 374:294-298(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310; SER-312; SER-991;
RP SER-997; SER-1317 AND SER-1322, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP FUNCTION.
RX PubMed=19028681; DOI=10.1074/jbc.m807554200;
RA Park Y., Yoon S.K., Yoon J.B.;
RT "The HECT domain of TRIP12 ubiquitinates substrates of the ubiquitin fusion
RT degradation pathway.";
RL J. Biol. Chem. 284:1540-1549(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312; SER-991; SER-1317 AND
RP SER-1322, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP FUNCTION, AND INTERACTION WITH SMARCC1.
RX PubMed=20829358; DOI=10.1074/jbc.m110.173997;
RA Keppler B.R., Archer T.K.;
RT "Ubiquitin-dependent and ubiquitin-independent control of subunit
RT stoichiometry in the SWI/SNF complex.";
RL J. Biol. Chem. 285:35665-35674(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-312 AND SER-942, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-12; SER-310; SER-1030; SER-1317 AND SER-1322, CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP FUNCTION.
RX PubMed=22884692; DOI=10.1016/j.cell.2012.06.039;
RA Gudjonsson T., Altmeyer M., Savic V., Toledo L., Dinant C., Grofte M.,
RA Bartkova J., Poulsen M., Oka Y., Bekker-Jensen S., Mailand N., Neumann B.,
RA Heriche J.K., Shearer R., Saunders D., Bartek J., Lukas J., Lukas C.;
RT "TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged
RT Chromosomes.";
RL Cell 150:697-709(2012).
RN [18]
RP INTERACTION WITH TRADD.
RX PubMed=22561347; DOI=10.1038/ncb2496;
RA Chio I.I., Sasaki M., Ghazarian D., Moreno J., Done S., Ueda T., Inoue S.,
RA Chang Y.L., Chen N.J., Mak T.W.;
RT "TRADD contributes to tumour suppression by regulating ULF-dependent p19Arf
RT ubiquitylation.";
RL Nat. Cell Biol. 14:625-633(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-100; SER-312;
RP SER-942; SER-991 AND SER-997, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1317 AND SER-1322, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP INVOLVEMENT IN CLABARS, AND VARIANTS CLABARS LEU-5; 338-ARG--SER-1992 DEL;
RP 352-ARG--SER-1992 DEL; VARIANT VAL-761; HIS-1557; GLN-1595 AND LEU-1840.
RX PubMed=27848077; DOI=10.1007/s00439-016-1743-x;
RA Bramswig N.C., Luedecke H.J., Pettersson M., Albrecht B., Bernier R.A.,
RA Cremer K., Eichler E.E., Falkenstein D., Gerdts J., Jansen S., Kuechler A.,
RA Kvarnung M., Lindstrand A., Nilsson D., Nordgren A., Pfundt R., Spruijt L.,
RA Surowy H.M., de Vries B.B., Wieland T., Engels H., Strom T.M.,
RA Kleefstra T., Wieczorek D.;
RT "Identification of new TRIP12 variants and detailed clinical evaluation of
RT individuals with non-syndromic intellectual disability with or without
RT autism.";
RL Hum. Genet. 136:179-192(2017).
RN [22]
RP INVOLVEMENT IN CLABARS, AND VARIANTS CLABARS VAL-761 AND PRO-1449--SER-1992
RP DEL.
RX PubMed=28251352; DOI=10.1007/s00439-017-1763-1;
RA Zhang J., Gambin T., Yuan B., Szafranski P., Rosenfeld J.A., Balwi M.A.,
RA Alswaid A., Al-Gazali L., Shamsi A.M.A., Komara M., Ali B.R., Roeder E.,
RA McAuley L., Roy D.S., Manchester D.K., Magoulas P., King L.E., Hannig V.,
RA Bonneau D., Denomme-Pichon A.S., Charif M., Besnard T., Bezieau S.,
RA Cogne B., Andrieux J., Zhu W., He W., Vetrini F., Ward P.A., Cheung S.W.,
RA Bi W., Eng C.M., Lupski J.R., Yang Y., Patel A., Lalani S.R., Xia F.,
RA Stankiewicz P.;
RT "Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes
RT intellectual disability with or without autism spectrum disorders, speech
RT delay, and dysmorphic features.";
RL Hum. Genet. 136:377-386(2017).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30982744; DOI=10.1016/j.molcel.2019.03.018;
RA Kweon S.M., Chen Y., Moon E., Kvederaviciute K., Klimasauskas S.,
RA Feldman D.E.;
RT "An adversarial DNA N6-methyladenine-sensor network preserves Polycomb
RT silencing.";
RL Mol. Cell 74:1138-1147(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase involved in ubiquitin fusion
CC degradation (UFD) pathway and regulation of DNA repair
CC (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion
CC degradation (UFD) pathway, a process that mediates ubiquitination of
CC protein at their N-terminus, regardless of the presence of lysine
CC residues in target proteins (PubMed:19028681). 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 (PubMed:22884692). In normal cells, mediates ubiquitination
CC and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor
CC suppressor required for p53/TP53 activation under oncogenic stress
CC (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and
CC TRIP12 are located in different cell compartments, preventing isoform
CC p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not
CC mediate ubiquitination of isoform p16-INK4a of CDKN2A
CC (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1,
CC leading to their degradation (PubMed:18627766). Ubiquitination and
CC degradation of target proteins is regulated by interaction with
CC proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction
CC between TRIP12 and target proteins (PubMed:20829358). Mediates
CC ubiquitination of ASXL1: following binding to N(6)-methyladenosine
CC methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its
CC degradation and subsequent inactivation of the PR-DUB complex
CC (PubMed:30982744). {ECO:0000269|PubMed:18627766,
CC ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519,
CC ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692,
CC ECO:0000269|PubMed:30982744}.
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:0000269|PubMed:18627766,
CC ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:30982744};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:20208519,
CC ECO:0000269|PubMed:30982744}.
CC -!- SUBUNIT: Interacts with MYC; leading to disrupt interaction with
CC isoform p19ARF/ARF of CDKN2A (PubMed:20208519). Interacts with TRADD;
CC leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A
CC (PubMed:22561347). Interacts with SMARCC1; leading to disrupt
CC interaction with SMARCE1 (PubMed:20829358).
CC {ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358,
CC ECO:0000269|PubMed:22561347}.
CC -!- INTERACTION:
CC Q14669; Q8N726: CDKN2A; NbExp=4; IntAct=EBI-308443, EBI-625922;
CC Q14669; P49286: MTNR1B; NbExp=3; IntAct=EBI-308443, EBI-1188341;
CC Q14669; P01106: MYC; NbExp=7; IntAct=EBI-308443, EBI-447544;
CC Q14669; P06748-1: NPM1; NbExp=2; IntAct=EBI-308443, EBI-354150;
CC Q14669; Q93009: USP7; NbExp=3; IntAct=EBI-308443, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:20208519}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q14669-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14669-2; Sequence=VSP_044328, VSP_044329;
CC Name=3;
CC IsoId=Q14669-3; Sequence=VSP_044326, VSP_044328;
CC Name=4;
CC IsoId=Q14669-4; Sequence=VSP_044327, VSP_044328, VSP_044329;
CC -!- DISEASE: Clark-Baraitser syndrome (CLABARS) [MIM:617752]: An autosomal
CC dominant disease characterized by intellectual disability, delayed
CC psychomotor development, behavioral abnormalities, variable dysmorphic
CC facial features, tall stature, obesity, and macrocephaly.
CC {ECO:0000269|PubMed:27848077, ECO:0000269|PubMed:28251352}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the UPL family. K-HECT subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14681.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAY14755.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA05837.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EU489742; ACC99349.1; -; mRNA.
DR EMBL; D28476; BAA05837.2; ALT_INIT; mRNA.
DR EMBL; AC009973; AAY14755.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC093384; AAY14681.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC105380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC114556; AAI14557.1; -; mRNA.
DR EMBL; BC113891; AAI13892.1; -; mRNA.
DR EMBL; L40383; AAC41731.1; -; mRNA.
DR CCDS; CCDS33391.1; -. [Q14669-1]
DR CCDS; CCDS63145.1; -. [Q14669-4]
DR CCDS; CCDS63146.1; -. [Q14669-3]
DR RefSeq; NP_001271143.1; NM_001284214.1. [Q14669-3]
DR RefSeq; NP_001271144.1; NM_001284215.2. [Q14669-2]
DR RefSeq; NP_001271145.1; NM_001284216.1. [Q14669-4]
DR RefSeq; NP_001335244.1; NM_001348315.1. [Q14669-3]
DR RefSeq; NP_001335245.1; NM_001348316.1. [Q14669-2]
DR RefSeq; NP_004229.1; NM_004238.2. [Q14669-1]
DR AlphaFoldDB; Q14669; -.
DR SMR; Q14669; -.
DR BioGRID; 114731; 187.
DR DIP; DIP-58584N; -.
DR IntAct; Q14669; 49.
DR MINT; Q14669; -.
DR STRING; 9606.ENSP00000373696; -.
DR GlyGen; Q14669; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14669; -.
DR MetOSite; Q14669; -.
DR PhosphoSitePlus; Q14669; -.
DR SwissPalm; Q14669; -.
DR BioMuta; TRIP12; -.
DR DMDM; 2499839; -.
DR EPD; Q14669; -.
DR jPOST; Q14669; -.
DR MassIVE; Q14669; -.
DR MaxQB; Q14669; -.
DR PaxDb; Q14669; -.
DR PeptideAtlas; Q14669; -.
DR PRIDE; Q14669; -.
DR ProteomicsDB; 60100; -. [Q14669-1]
DR ProteomicsDB; 60316; -.
DR ProteomicsDB; 60326; -.
DR Antibodypedia; 34396; 79 antibodies from 23 providers.
DR DNASU; 9320; -.
DR Ensembl; ENST00000283943.9; ENSP00000283943.4; ENSG00000153827.14. [Q14669-1]
DR Ensembl; ENST00000389044.8; ENSP00000373696.4; ENSG00000153827.14. [Q14669-3]
DR Ensembl; ENST00000389045.7; ENSP00000373697.3; ENSG00000153827.14. [Q14669-4]
DR GeneID; 9320; -.
DR KEGG; hsa:9320; -.
DR UCSC; uc002vpw.3; human. [Q14669-1]
DR CTD; 9320; -.
DR DisGeNET; 9320; -.
DR GeneCards; TRIP12; -.
DR HGNC; HGNC:12306; TRIP12.
DR HPA; ENSG00000153827; Low tissue specificity.
DR MalaCards; TRIP12; -.
DR MIM; 604506; gene.
DR MIM; 617752; phenotype.
DR neXtProt; NX_Q14669; -.
DR OpenTargets; ENSG00000153827; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA36985; -.
DR VEuPathDB; HostDB:ENSG00000153827; -.
DR eggNOG; KOG0168; Eukaryota.
DR eggNOG; KOG0170; Eukaryota.
DR GeneTree; ENSGT00940000156517; -.
DR HOGENOM; CLU_000366_2_0_1; -.
DR InParanoid; Q14669; -.
DR OrthoDB; 34110at2759; -.
DR PhylomeDB; Q14669; -.
DR TreeFam; TF323674; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q14669; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q14669; -.
DR SIGNOR; Q14669; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9320; 85 hits in 1138 CRISPR screens.
DR ChiTaRS; TRIP12; human.
DR GeneWiki; TRIP12; -.
DR GenomeRNAi; 9320; -.
DR Pharos; Q14669; Tbio.
DR PRO; PR:Q14669; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14669; protein.
DR Bgee; ENSG00000153827; Expressed in calcaneal tendon and 210 other tissues.
DR ExpressionAtlas; Q14669; baseline and differential.
DR Genevisible; Q14669; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:2000780; P:negative regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IDA: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; IDA: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 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Autism spectrum disorder;
KW Disease variant; DNA damage; DNA repair; Intellectual disability; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CHAIN 2..1992
FT /note="E3 ubiquitin-protein ligase TRIP12"
FT /id="PRO_0000173872"
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 797..817
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 938..1080
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1407..1433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1496..1570
FT /note="K-box"
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 121..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..218
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..338
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..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 797..812
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 941..968
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..1066
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1959
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000305"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:G5E870"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 942
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 997
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LP64"
FT MOD_RES 1030
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 1322
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
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"
FT VAR_SEQ 32
FT /note="G -> GRSHLGQAKHKGYSPPESRKSNSKAPKVQSNTTSELSRGHLSK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044326"
FT VAR_SEQ 33..335
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044327"
FT VAR_SEQ 380
FT /note="A -> AAASSSV (in isoform 2, isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:20208519"
FT /id="VSP_044328"
FT VAR_SEQ 784
FT /note="E -> EAAHQVGEDEISLSTLGRVYTIDFNSMQ (in isoform 2 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:20208519"
FT /id="VSP_044329"
FT VARIANT 5
FT /note="P -> L (in CLABARS; unknown pathological
FT significance; dbSNP:rs1300458163)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080431"
FT VARIANT 338..1992
FT /note="Missing (in CLABARS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080432"
FT VARIANT 352..1992
FT /note="Missing (in CLABARS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080433"
FT VARIANT 761
FT /note="A -> V (in CLABARS; dbSNP:rs373429636)"
FT /evidence="ECO:0000269|PubMed:27848077,
FT ECO:0000269|PubMed:28251352"
FT /id="VAR_080434"
FT VARIANT 1449..1992
FT /note="Missing (in CLABARS)"
FT /evidence="ECO:0000269|PubMed:28251352"
FT /id="VAR_080435"
FT VARIANT 1557
FT /note="D -> H (in CLABARS)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080436"
FT VARIANT 1595
FT /note="R -> Q (in CLABARS; dbSNP:rs1553602821)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080437"
FT VARIANT 1840
FT /note="S -> L (in CLABARS; dbSNP:rs866079762)"
FT /evidence="ECO:0000269|PubMed:27848077"
FT /id="VAR_080438"
FT MUTAGEN 1959
FT /note="C->A: Abolishes E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:20208519"
FT CONFLICT 1969..1992
FT /note="SSIEIMREKLLIAAREGQQSFHLS -> QALRYA (in Ref. 5;
FT AAC41731)"
FT /evidence="ECO:0000305"
FT CONFLICT Q14669-2:380
FT /note="A -> T (in Ref. 1; ACC99349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1992 AA; 220434 MW; 294A7C063A3332DE CRC64;
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSA VIVPQPEDPD RANTSERQKT
GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPKALQHTES PSETNKPHSK SKKRHLDQEQ
QLKSAQSPST SKAHTRKSGA TGGSRSQKRK RTESSCVKSG SGSESTGAEE RSAKPTKLAS
KSATSAKAGC STITDSSSAA STSSSSSAVA SASSTVPPGA RVKQGKDQNK ARRSRSASSP
SPRRSSREKE QSKTGGSSKF DWAARFSPKV SLPKTKLSLP GSSKSETSKP GPSGLQAKLA
SLRKSTKKRS ESPPAELPSL RRSTRQKTTG SCASTSRRGS GLGKRGAAEA RRQEKMADPE
SNQEAVNSSA ARTDEAPQGA 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 NPLANSNTSG YSESKKDDAR AQLMKEDPEL AKSFIKTLFG
VLYEVYSSSA GPAVRHKCLR AILRIIYFAD AELLKDVLKN HAVSSHIASM LSSQDLKIVV
GALQMAEILM QKLPDIFSVY FRREGVMHQV KHLAESESLL TSPPKACTNG SGSMGSTTSV
SSGTATAATH AAADLGSPSL QHSRDDSLDL SPQGRLSDVL KRKRLPKRGP RRPKYSPPRD
DDKVDNQAKS PTTTQSPKSS FLASLNPKTW GRLSTQSNSN NIEPARTAGG SGLARAASKD
TISNNREKIK GWIKEQAHKF VERYFSSENM DGSNPALNVL QRLCAATEQL NLQVDGGAEC
LVEIRSIVSE SDVSSFEIQH SGFVKQLLLY LTSKSEKDAV SREIRLKRFL HVFFSSPLPG
EEPIGRVEPV GNAPLLALVH KMNNCLSQME QFPVKVHDFP SGNGTGGSFS LNRGSQALKF
FNTHQLKCQL QRHPDCANVK QWKGGPVKID PLALVQAIER YLVVRGYGRV REDDEDSDDD
GSDEEIDESL AAQFLNSGNV RHRLQFYIGE HLLPYNMTVY QAVRQFSIQA EDERESTDDE
SNPLGRAGIW TKTHTIWYKP VREDEESNKD CVGGKRGRAQ TAPTKTSPRN AKKHDELWHD
GVCPSVSNPL EVYLIPTPPE NITFEDPSLD VILLLRVLHA ISRYWYYLYD 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 IEIMREKLLI
AAREGQQSFH LS
