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Details on Person UniProt:Q14669 TRIP12

Class:Id	ReferenceGeneProduct:66421
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-1992 added on Sat February 7 2015;initiator methionine:1 for 66421 removed on Fri Nov 03 2023;initiator methionine: for 66421 added on Fri Nov 03 2023;initiator methionine: for 66421 removed on Fri Aug 15 2025;initiator methionine:1 for 66421 added on Fri Aug 15 2025;chain:2-1992 for 66421 removed on Fri Feb 20 2026;chain:2-2067 for 66421 added on Fri Feb 20 2026
_displayName	UniProt:Q14669 TRIP12
_timestamp	2026-05-15 21:12:03
chain	initiator methionine:1 chain:2-2067
checksum	63A421E2402AC29D
comment	FUNCTION E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692, PubMed:40419785). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). 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 (PubMed:22884692). 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 (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). 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 (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744).CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.ACTIVITY REGULATION Preferentially modifies 'Lys-29' in the proximal ubiquitin in a 'Lys-48'-linked di-ubiquitin chain.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with MYC; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A (PubMed:20208519). Interacts with TRADD; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A (PubMed:22561347). Interacts with SMARCC1; leading to disrupt interaction with SMARCE1 (PubMed:20829358).INTERACTION The ARM domain allows tandem binding of ubiquitins.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the UPL family. K-HECT subfamily.SEQUENCE CAUTION Extended N-terminus.
description	recommendedName: E3 ubiquitin-protein ligase TRIP12 ecNumber evidence="6 8 14"2.3.2.26 alternativeName: E3 ubiquitin-protein ligase for Arf shortName: ULF alternativeName: HECT-type E3 ubiquitin transferase TRIP12 alternativeName: Thyroid receptor-interacting protein 12 shortName: TR-interacting protein 12 shortName: TRIP-12
geneName	TRIP12 KIAA0045 ULF
identifier	Q14669
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Autism spectrum disorder Disease variant DNA damage DNA repair Intellectual disability Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transferase Ubl conjugation pathway
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 [InstanceEdit:9989145] Weiser, Joel, 2026-05-15
name	TRIP12
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8996934] ENSEMBL:ENSG00000153827 TRIP12 [Homo sapiens]
secondaryIdentifier	TRIPC_HUMAN A0A6Q8PHK0 D4HL82 Q14CA3 Q14CF1 Q15644 Q53R87 Q53TE7
sequenceLength	2067
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8970330] UniProt:Q14669-1 TRIP12 [Homo sapiens] [ReferenceIsoform:8970331] UniProt:Q14669-2 TRIP12 [Homo sapiens] [ReferenceIsoform:8970332] UniProt:Q14669-3 TRIP12 [Homo sapiens] [ReferenceIsoform:8970333] UniProt:Q14669-4 TRIP12 [Homo sapiens] [ReferenceIsoform:9983299] Unknown:Q14669-6 TRIP12 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:976046] TRIP12 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8856896] TRIP12 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8864474] Ub-C1959-TRIP12 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8864541] Ub-C1959-TRIP12 [nucleoplasm] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:8864517] S-(glycyl)-L-cysteine (Cys-Gly) at 1959
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No pathways have been reviewed or authored by UniProt:Q14669 TRIP12 (66421)