Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000209 protein polyubiquitination	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) annotation to protein polyubiquitination, a family-level capability of UBC E2s. UBE2T can drive polyubiquitination in vitro and polyubiquitinates BRCA1 in overexpression settings, but its physiological FA role is monoubiquitination of FANCD2/FANCI. Reason: Not incorrect — UBE2T has demonstrable polyubiquitination capacity (PMID:20061386, PMID:19887602) — but polyubiquitination is not the core biological function of UBE2T, which is site-specific monoubiquitination in the FA pathway. Retained as a valid non-core annotation. Supporting Evidence: PMID:19887602 BRCA1 to be polyubiquitinated by incubation with
GO:0061631 ubiquitin conjugating enzyme activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the core E2 ubiquitin-conjugating enzyme activity. This is the defining molecular function of UBE2T. Reason: Well supported at both the family (IBA) and gene-specific experimental levels. UBE2T is the E2 essential for the FA pathway, accepting ubiquitin from E1 and, with FANCL, transferring it to FANCD2/FANCI. This is the correctly specific MF term for an E2 and represents the core function. Supporting Evidence: PMID:16916645 UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway.
GO:0006974 DNA damage response	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation placing UBE2T in the DNA damage response, consistent with its role in the FA pathway triggered by replication-blocking DNA lesions. Reason: Consistent with experimental evidence: UBE2T-catalyzed FANCD2 monoubiquitination is a DNA-damage/S-phase-restricted event and UBE2T depletion produces the DNA-damage-associated chromosomal abnormalities of FA. Supporting Evidence: PMID:17938197 The Fanconi anemia (FA) nuclear core complex and the E2 ubiquitin-conjugating enzyme UBE2T are required for the S phase and DNA damage-restricted monoubiquitination of FANCD2.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (from UniProt subcellular-location mapping) to nucleus, matching the UniProt SUBCELLULAR LOCATION and experimental data. Reason: UBE2T is a nuclear protein that accumulates on chromatin; the nuclear location is experimentally established and is where UBE2T functions in the FA pathway. Supporting Evidence: PMID:17938197 UBE2T and FANCD2 access this subcellular fraction independently of the FA core complex.
GO:0019787 ubiquitin-like protein transferase activity	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (ARBA) annotation to a broad parent molecular-function term encompassing ubiquitin/UBL transfer. Reason: Correct but less specific than the E2-specific GO:0061631 that is also annotated. A broader electronic term is acceptable; no change needed, though it is not the most informative representation of UBE2T's activity.
GO:0032446 protein modification by small protein conjugation	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (ARBA) annotation to a broad parent process for ubiquitin/UBL conjugation. Reason: A correct high-level process term consistent with UBE2T's ubiquitin-conjugating role. Broader than the specific monoubiquitination/ICL-repair processes but not wrong; acceptable as a general electronic annotation.
GO:0061631 ubiquitin conjugating enzyme activity	IEA GO_REF:0000003	ACCEPT	Summary: Electronic annotation from EC 2.3.2.23 mapping to E2 ubiquitin-conjugating enzyme activity — the core molecular function of UBE2T. Reason: EC 2.3.2.23 is assigned to UBE2T with experimental support (PMID:20061386) and maps correctly to the E2 activity term, which is also supported experimentally and phylogenetically. Core function.
GO:0005515 protein binding	IPI PMID:24389026 Structure of the human FANCL RING-Ube2T complex reveals dete...	KEEP AS NON CORE	Summary: IPI protein-binding annotation from the FANCL RING–UBE2T structure (interactor FANCL, Q9NW38). This physical interaction is central to UBE2T function but is captured uninformatively here. Reason: The FANCL interaction is real and important, but 'protein binding' (GO:0005515) is uninformative; the same interaction is better represented by the ubiquitin-protein-ligase-binding annotations (GO:0031625). Retained as valid but non-core; the informative term is preferred for core representation. Supporting Evidence: PMID:24389026 FANCL exclusively formed a complex with Ube2T
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: IPI protein-binding annotation to GNB2 (P62879) from a large-scale neurodegenerative-disease yeast two-hybrid interactome. Reason: A high-throughput binary interaction of unclear biological significance for UBE2T's function; also recorded in UniProt INTERACTION. Generic 'protein binding' is uninformative. Retained as non-core rather than removed, since the interaction is documented.
GO:0016567 protein ubiquitination	IEA GO_REF:0000041	ACCEPT	Summary: Electronic annotation (UniPathway mapping) to the general protein ubiquitination process. Reason: A correct broad process term for an E2 ubiquitin-conjugating enzyme. Broader than the specific monoubiquitination role but accurate; acceptable as a general electronic annotation.
GO:0005634 nucleus	EXP PMID:19887602 Ubiquitination and downregulation of BRCA1 by ubiquitin-conj...	ACCEPT	Summary: Experimental nuclear localization of UBE2T in breast cancer cells. Reason: Direct experimental support for the nuclear localization that is consistent with UBE2T's function; matches UniProt SUBCELLULAR LOCATION 'Nucleus'. Supporting Evidence: PMID:19887602 UBE2T interacted and colocalized with the BRCA1/BRCA1-associated RING domain protein (BARD1) complex.
GO:0061631 ubiquitin conjugating enzyme activity	EXP PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	ACCEPT	Summary: Experimental demonstration of UBE2T E2 ubiquitin-conjugating enzyme activity (catalytic activity underlying EC 2.3.2.23). Reason: David et al. purified and assayed UBE2T among all human E2s, confirming its E2 conjugating activity. Core molecular function. Supporting Evidence: PMID:20061386 the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8852130	ACCEPT	Summary: Reactome (TAS) nucleoplasm location, from the reaction in which E1 (UBA1) charges nuclear E2 enzymes with ubiquitin. Reason: Nucleoplasm is a valid, appropriately specific nuclear location for UBE2T, consistent with its nuclear/chromatin localization and its function there in the FA pathway.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785361	ACCEPT	Summary: Reactome (TAS) nucleoplasm location, from the FANCD2:FANCI monoubiquitination reaction of the FA pathway. Reason: Consistent with UBE2T functioning in the nucleus/on chromatin during FANCD2/FANCI monoubiquitination. Valid location annotation.
GO:0061631 ubiquitin conjugating enzyme activity	IDA PMID:19589784 FANCI binds branched DNA and is monoubiquitinated by UBE2T-F...	ACCEPT	Summary: Direct assay (IDA) of UBE2T E2 activity: the UBE2T-FANCL pair monoubiquitinates FANCI on Lys-523 in vitro. Reason: Direct experimental support for UBE2T's E2 conjugating enzyme activity in the FA pathway context. Core molecular function. Supporting Evidence: PMID:19589784 FANCI can be ubiquitinated on Lys-523 by the UBE2T-FANCL pair in vitro
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785342	ACCEPT	Summary: Reactome (TAS) nucleoplasm location, from the reaction in which the FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex. Reason: Valid nuclear location consistent with UBE2T acting at ICL-DNA/chromatin within the FA pathway.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788385	ACCEPT	Summary: Reactome (TAS) nucleoplasm location, associated with FA-pathway reactions at ICL-DNA. Reason: Valid, appropriately specific nuclear location for UBE2T consistent with its site of action.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788392	ACCEPT	Summary: Reactome (TAS) nucleoplasm location, associated with FA-pathway reactions at ICL-DNA. Reason: Valid nuclear location consistent with UBE2T's nuclear/chromatin function in the FA pathway.
GO:0003682 chromatin binding	IDA PMID:17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recru...	KEEP AS NON CORE	Summary: IDA chromatin-binding annotation reflecting UBE2T's constitutive presence in and accumulation on the chromatin fraction, where it forms the active E2/E3 holoenzyme with FANCL. Reason: Experimentally supported chromatin association (UBE2T is constitutively present in the chromatin compartment and FANCD2 monoubiquitination is regulated by localization to chromatin). This localization/binding supports but is not itself the core catalytic function; retained as non-core. Supporting Evidence: PMID:17938197 The E2-conjugating enzyme UBE2T is constitutively present in this compartment.
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	MODIFY	Summary: IDA annotation to the general ubiquitin-protein transferase activity term based on UBE2T's demonstrated role as the E2 that transfers ubiquitin to FANCD2. Reason: Correct in essence but not the most specific/informative term. UBE2T is an E2 ubiquitin-conjugating enzyme; the E2-specific molecular function GO:0061631 (ubiquitin conjugating enzyme activity) better represents its activity than the broader GO:0004842 (which also covers E3 ligase activity). Proposed replacements: ubiquitin conjugating enzyme activity Supporting Evidence: PMID:16916645 UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway.
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recru...	MODIFY	Summary: IDA annotation to the general ubiquitin-protein transferase activity term from the reconstituted FANCD2 monoubiquitination system. Reason: As above, the E2-specific term GO:0061631 is the more accurate/informative molecular function for UBE2T than the broader GO:0004842. Proposed replacements: ubiquitin conjugating enzyme activity Supporting Evidence: PMID:17938197 the E2 ubiquitin-conjugating enzyme UBE2T are required for the S phase and DNA damage-restricted monoubiquitination of FANCD2
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:19111657 Mechanistic insight into site-restricted monoubiquitination ...	MODIFY	Summary: IDA annotation to general ubiquitin-protein transferase activity from the minimal Ube2t/FANCL FANCD2 monoubiquitination reconstitution. Reason: Essence is correct but the E2-specific GO:0061631 is the more precise molecular function term for UBE2T. Proposed replacements: ubiquitin conjugating enzyme activity Supporting Evidence: PMID:19111657 we minimally reconstitute this monoubiquitination reaction with Ube2t and the FANCL protein
GO:0005634 nucleus	TAS PMID:17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recru...	ACCEPT	Summary: TAS nuclear localization annotation, consistent with experimental and UniProt-curated nuclear localization. Reason: UBE2T is nuclear and functions there in the FA pathway; the nuclear location is well established. Supporting Evidence: PMID:17938197 UBE2T and FANCD2 access this subcellular fraction independently of the FA core complex.
GO:0006281 DNA repair	IMP PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	MODIFY	Summary: IMP annotation to DNA repair: UBE2T depletion impairs mitomycin-C-induced repair and produces the chromosomal abnormalities characteristic of FA. Reason: Correct but too general. UBE2T's function is specifically in the Fanconi anemia DNA interstrand cross-link (ICL) repair pathway (the IMP evidence uses mitomycin C, an ICL-inducing agent). The more specific process term GO:0036297 (interstrand cross-link repair) better represents this role. Proposed replacements: interstrand cross-link repair Supporting Evidence: PMID:16916645 DNA damage in UBE2T-depleted cells leads to the formation of abnormal chromosomes that are a hallmark of Fanconi anemia.
GO:0006513 protein monoubiquitination	IDA PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	ACCEPT	Summary: IDA annotation to protein monoubiquitination — the central FA-pathway activity of UBE2T (monoubiquitination of FANCD2, required in vivo). Reason: Directly supported and represents the core biological process catalyzed by UBE2T with FANCL: site-specific monoubiquitination of FANCD2. Supporting Evidence: PMID:16916645 is required for the monoubiquitination of FANCD2 in vivo
GO:0006513 protein monoubiquitination	IDA PMID:17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recru...	ACCEPT	Summary: IDA annotation to protein monoubiquitination from the study establishing that FANCD2 monoubiquitination requires UBE2T and is regulated by chromatin localization. Reason: Core biological process; directly supported by the requirement of UBE2T for DNA-damage-restricted FANCD2 monoubiquitination. Supporting Evidence: PMID:17938197 FANCD2 monoubiquitination is therefore not regulated by multiprotein complex assembly but by the formation of an active E2/E3 holoenzyme on chromatin.
GO:0006513 protein monoubiquitination	IDA PMID:19111657 Mechanistic insight into site-restricted monoubiquitination ...	ACCEPT	Summary: IDA annotation to protein monoubiquitination from the minimal reconstitution showing FANCI restricts the modification to the physiological FANCD2 substrate lysine. Reason: Core biological process directly catalyzed by UBE2T with FANCL (site-specific FANCD2 monoubiquitination). Supporting Evidence: PMID:19111657 addition of the FANCI protein enhances monoubiquitination and also restricts it to the in vivo substrate lysine residue on FANCD2
GO:0006974 DNA damage response	IMP PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	ACCEPT	Summary: IMP annotation to DNA damage response, from loss-of-function evidence linking UBE2T to the DNA-damage-activated FA pathway. Reason: UBE2T operates in the DNA-damage/replication-stress-activated FA pathway; its depletion produces the DNA-damage-induced chromosomal instability of FA. Consistent with the IBA DNA damage response annotation. Supporting Evidence: PMID:16916645 The Fanconi anemia pathway is required for the efficient repair of damaged DNA.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	ACCEPT	Summary: IPI annotation for binding the E3 ubiquitin-protein ligase FANCL (Q9NW38), the cognate partner of UBE2T in the FA pathway. Reason: Informative and central: the UBE2T-FANCL E2-E3 interaction is required for FANCD2 monoubiquitination. FANCL is the RING E3 ligase subunit of the FA core complex. This is the informative counterpart to the generic 'protein binding' annotation. Supporting Evidence: PMID:16916645 UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex
GO:0031625 ubiquitin protein ligase binding	IPI PMID:17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recru...	ACCEPT	Summary: IPI annotation for UBE2T binding the E3 ligase FANCL, forming the active E2/E3 holoenzyme on chromatin. Reason: Supported and functionally central; the FANCL interaction underlies UBE2T's role in FANCD2 monoubiquitination. Supporting Evidence: PMID:17938197 the formation of an active E2/E3 holoenzyme on chromatin
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19111657 Mechanistic insight into site-restricted monoubiquitination ...	ACCEPT	Summary: IPI annotation for UBE2T-FANCL binding; the FANCL RWD-like domain stimulates the UBE2T-catalyzed reaction. Reason: Directly supported and central to function; FANCL binding is required for efficient FANCD2 monoubiquitination. Supporting Evidence: PMID:19111657 monoubiquitination is stimulated by a conserved RWD-like domain in FANCL
GO:0051865 protein autoubiquitination	IDA PMID:16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes ...	KEEP AS NON CORE	Summary: IDA annotation to protein autoubiquitination: UBE2T undergoes automonoubiquitination (Lys-91), stimulated by FANCL, reported to inactivate the enzyme. Reason: Experimentally supported but a regulatory/self-limiting modification rather than UBE2T's core catalytic output (FANCD2/FANCI monoubiquitination). The functional consequence is also disputed between reports (PMID:16916645 inactivating; PMID:19111657 no effect). Retained as non-core. Supporting Evidence: PMID:16916645 UBE2T undergoes automonoubiquitination in vivo. This monoubiquitination is stimulated by the presence of the FANCL protein and inactivates UBE2T.
GO:0051865 protein autoubiquitination	IDA PMID:19111657 Mechanistic insight into site-restricted monoubiquitination ...	KEEP AS NON CORE	Summary: IDA annotation to protein autoubiquitination (Lys-91/Lys-182) from the mechanistic reconstitution study. Reason: Supported but regulatory and non-core; here autoubiquitination was reported not to affect E2 activity, underscoring that it is a modulatory feature rather than the enzyme's core function.
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MODIFY	Summary: IDA annotation to general ubiquitin-protein transferase activity from the systematic in-vitro characterization of all human E2 enzymes. Reason: Correct but too general; the E2-specific GO:0061631 (ubiquitin conjugating enzyme activity) more precisely captures UBE2T's molecular function. Proposed replacements: ubiquitin conjugating enzyme activity Supporting Evidence: PMID:20061386 the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized
GO:0035519 protein K29-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K29-linked ubiquitination from an in-vitro, E3-free assay of intrinsic E2 lysine preference. Reason: Derived from a systematic in-vitro study performed in the absence of an E3 ligase, measuring the intrinsic lysine preferences of purified E2s. This does not reflect UBE2T's physiological function (site-specific monoubiquitination of FANCD2/FANCI with FANCL); UniProt notes the all-seven-lysine polyubiquitination is an in-vitro capacity. Over-annotation of the biological role. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines
GO:0044314 protein K27-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K27-linked ubiquitination from the in-vitro, E3-free E2 lysine-preference assay. Reason: In-vitro capacity measured without an E3 ligase; not representative of UBE2T's physiological monoubiquitination role in the FA pathway. Over-annotation. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines
GO:0070534 protein K63-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K63-linked ubiquitination from the in-vitro, E3-free E2 lysine-preference assay. Reason: Reflects intrinsic in-vitro lysine preference measured without an E3; not the physiological FA-pathway function of UBE2T. Over-annotation of biological role. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines
GO:0070936 protein K48-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K48-linked ubiquitination from the in-vitro, E3-free E2 lysine-preference assay. Reason: In-vitro capacity determined in the absence of an E3 ligase; does not represent UBE2T's physiological function. Over-annotation of biological role. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines
GO:0070979 protein K11-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K11-linked ubiquitination from the in-vitro, E3-free E2 lysine-preference assay. Reason: Intrinsic in-vitro lysine preference measured without an E3; not the physiological monoubiquitination role of UBE2T. Over-annotation of biological role. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines
GO:0085020 protein K6-linked ubiquitination	IDA PMID:20061386 The E2 ubiquitin-conjugating enzymes direct polyubiquitinati...	MARK AS OVER ANNOTATED	Summary: IDA annotation to K6-linked ubiquitination from the in-vitro, E3-free E2 lysine-preference assay. Reason: Reflects intrinsic in-vitro lysine usage measured without an E3 ligase; not representative of UBE2T's physiological FA-pathway function. Over-annotation. Supporting Evidence: PMID:20061386 Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines

Core Functions

E2 ubiquitin-conjugating enzyme of the Fanconi anemia pathway: accepts ubiquitin from the E1 activating enzyme via active-site Cys86 and, partnered with the cognate RING E3 ligase FANCL, catalyzes the DNA-damage-induced, site-specific monoubiquitination of FANCD2 (and FANCI) on chromatin, the central activating step of interstrand cross-link repair.

Molecular Function:

ubiquitin conjugating enzyme activity

Directly Involved In:

protein monoubiquitination interstrand cross-link repair DNA damage response

Cellular Locations:

nucleoplasm

Supporting Evidence:

PMID:16916645
UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway. UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex, and is required for the monoubiquitination of FANCD2 in vivo.
PMID:19111657
addition of the FANCI protein enhances monoubiquitination and also restricts it to the in vivo substrate lysine residue on FANCD2

References

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:16916645

UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation.

PMID:17938197

UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination.

PMID:19111657

Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI.

PMID:19589784

FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.

PMID:19887602

Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells.

PMID:20061386

The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines.

PMID:24389026

Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:26046368

Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.

Reactome:R-HSA-6785342

FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex

Reactome:R-HSA-6785361

Monoubiquitination of FANCD2:FANCI

Reactome:R-HSA-6788385

The complex of ATR and ATRIP is recruited to ICL-DNA

Reactome:R-HSA-6788392

ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA

Reactome:R-HSA-8852130

UBA1 conjugates ubiquitin to nuclear E2 enzymes

Deep Research

Affinage

(UBE2T-deep-research-affinage.md)

Affinage mechanistic annotation for UBE2T (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 37 citations

Affinage mechanistic annotation for UBE2T (human)

Current model (mechanistic narrative)

UBE2T is the dedicated E2 ubiquitin-conjugating enzyme of the Fanconi anemia (FA) DNA interstrand crosslink repair pathway, pairing with the E3 ligase FANCL to catalyze monoubiquitination of FANCD2 and FANCI on chromatin [PMID:16916645, PMID:19111657]. In vitro reconstitution established that FANCD2 monoubiquitination minimally requires UBE2T plus the FANCL RWD-like domain, with FANCI both stimulating the reaction and restricting it to the physiological substrate lysine K561, while FANCI itself is monoubiquitinated at K523 [PMID:19111657, PMID:19589784]. A crystal structure of the FANCL RING–UBE2T complex defined an extensive electrostatic and hydrophobic interface beyond the generic E2–E3 contact that determines selective recognition of UBE2T over other E2 enzymes PMID:24389026. This activity is governed by DNA damage-induced recruitment of UBE2T and FANCD2 to chromatin to form an active E2/E3 holoenzyme rather than by stable assembly of the core complex, and is negatively autoregulated by FANCL-stimulated UBE2T automonoubiquitination [PMID:16916645, PMID:17938197]. Biallelic loss-of-function mutations in UBE2T cause Fanconi anemia (FA-T subtype): patient cells lack FANCD2/FANCI monoubiquitination, fail to form FANCD2 foci, and are hypersensitive to crosslinkers, defects complemented by wild-type UBE2T [PMID:26119737, PMID:26046368, PMID:26085575]. Beyond crosslink repair, UBE2T contributes to nucleotide excision repair and to the resolution of R-loops and transcription-replication conflicts to maintain genome stability [PMID:22615860, PMID:36928776]. UBE2T protein abundance is controlled post-translationally by CaMKII-δ9-mediated phosphorylation-dependent degradation and by NEDD4L-directed proteasomal turnover [PMID:31481791, PMID:34838005]. In cancer, UBE2T acts as an oncogenic ubiquitin conjugator that ubiquitinates diverse substrates—including p53, RACK1, Akt, RPL6, CDC42, FOXO1, and CBX6—frequently through K48- or K63-linked chains and often independently of or in cooperation with various E3 ligases, thereby activating Wnt/β-catenin, PI3K/AKT, and related signaling outputs [PMID:33323973, PMID:35169125, PMID:36156329, PMID:39915000, PMID:39716485].

Affinage mechanism profile (Affinage's own GO/Reactome grounding)

molecular_activity: GO:0140096 catalytic activity, acting on a protein, GO:0016740 transferase activity
localization: GO:0005634 nucleus, GO:0000228 nuclear chromosome
pathway (Reactome): R-HSA-73894 DNA Repair, R-HSA-392499 Metabolism of proteins, R-HSA-1643685 Disease, R-HSA-162582 Signal Transduction
partners: FANCL, FANCD2, FANCI, RNF8, NEDD4L, TRIM25, TRIM28, MULE
complexes: Fanconi anemia core complex (FANCL E2/E3 holoenzyme)

Dated findings (citation-anchored)

Year	Confidence	Finding	PMIDs	Journal
2006	High	UBE2T is the E2 ubiquitin-conjugating enzyme essential for the Fanconi anemia pathway; it binds to FANCL (the E3 ubiquitin ligase subunit of the FA core complex) and is required for monoubiquitination of FANCD2 in vivo. UBE2T also undergoes automonoubiquitination stimulated by FANCL, which inactivates UBE2T, providing a self-inactivation/negative regulatory mechanism.	PMID:16916645	Molecular cell
2008	High	In vitro reconstitution of FANCD2 monoubiquitination requires minimally UBE2T and FANCL. A conserved RWD-like domain in FANCL stimulates monoubiquitination. Addition of FANCI enhances monoubiquitination and restricts it to the in vivo substrate lysine residue on FANCD2 (K561).	PMID:19111657	Molecular cell
2007	High	UBE2T and FANCD2 are each recruited to chromatin independently of the FA core complex. The E3 ligase activity of the FA core complex is determined not by its stable assembly but by its DNA damage-induced localization to chromatin. Therefore, FANCD2 monoubiquitination is regulated by formation of an active E2/E3 holoenzyme on chromatin rather than by multiprotein complex assembly.	PMID:17938197	Molecular and cellular biology
2009	High	FANCI is monoubiquitinated on Lys-523 by the UBE2T–FANCL pair in vitro. FANCI and its C-terminal fragment possess a DNA binding activity that prefers branched DNA structures.	PMID:19589784	The Journal of biological chemistry
2014	High	Crystal structure of the FANCL RING domain in complex with UBE2T revealed a specific and extensive network of electrostatic and hydrophobic interactions beyond the generic E2–E3 interface that determines selective recognition of UBE2T over other E2 enzymes by FANCL.	PMID:24389026	Structure
2012	Medium	UBE2T (and FANCM) are required for nucleotide excision repair (NER) in addition to their role in ICL repair. UBE2T-deficient DT40 cells are unexpectedly sensitive to UV-induced DNA damage; genetic epistasis experiments indicate UBE2T collaborates to promote NER rather than translesion bypass, and UBE2T deficiency impairs efficient removal of UV-induced cyclobutane pyrimidine dimers.	PMID:22615860	PloS one
2015	High	Biallelic loss-of-function mutations in UBE2T cause Fanconi anemia (FA-T subtype). Patient fibroblasts lack FANCD2 and FANCI monoubiquitination, fail to form FANCD2 foci after MMC treatment, and are hypersensitive to crosslinking agents; these defects are complemented by wild-type UBE2T expression. A missense mutation (p.Gln2Glu) abolishes FANCD2 monoubiquitination and FANCL interaction.	PMID:26119737, PMID:26046368, PMID:26085575	Cell reports / American journal of human genetics
2019	High	CaMKII-δ9 phosphorylates UBE2T and targets it for degradation, thereby disrupting UBE2T-dependent DNA repair, causing accumulation of DNA damage and genome instability in cardiomyocytes, and promoting cardiomyopathy and heart failure.	PMID:31481791	Nature cell biology
2011	Medium	Hypoxia rapidly and potently reduces UBE2T mRNA levels in cancer cell lines through reduced promoter activity (HIF-independent, not due to mRNA or protein stability changes), correlating with increased sensitivity to interstrand crosslinking agents and disruption of the FA pathway.	PMID:21722982	Radiotherapy and oncology
2017	Medium	A novel allosteric binding pocket on UBE2T was identified through fragment screening; fragments binding to this site inhibit ubiquitin conjugation in vitro.	PMID:28437106	Journal of medicinal chemistry
2017	Medium	A zinc ion from a fragment library contaminant binds the active-site cysteine of UBE2T and induces a domain swap leading to cyclic trimerization in an open-ended linear assembly, revealing structural plasticity of the UBE2T active site.	PMID:28933844	Journal of medicinal chemistry
2019	Medium	A small-molecule inhibitor of UBE2T/FANCL-mediated FANCD2 monoubiquitylation was identified that sensitizes cells to the DNA cross-linking agent carboplatin, establishing UBE2T enzymatic activity as pharmacologically targetable.	PMID:31525021	ACS chemical biology
2020	Medium	UBE2T forms an E2–E3 pair with RNF8 and monoubiquitinates histone variant H2AX/γH2AX upon radiation exposure. This monoubiquitination facilitates CHK1 phosphorylation/activation and CHK1 release from chromatin to cytosol. E2-enzyme-deficient mutation C86A of UBE2T and monoubiquitination-site-deficient mutation K119/120R of H2AX both abrogate CHK1 activation.	PMID:33087136	Journal of experimental & clinical cancer research
2020	Medium	UBE2T promotes Wnt/β-catenin signaling hyperactivation in gastric cancer by mediating ubiquitination and proteasomal degradation of RACK1 at lysine residues K172, K225, and K257, independently of an E3 ligase.	PMID:33323973	Oncogene
2020	Low	UBE2T promotes ubiquitination and degradation of FOXO1 in non-small cell lung cancer, activating Wnt/β-catenin signaling, and promoting EMT and radiation resistance.	PMID:32590022	Cancer letters
2017	Low	UBE2T promotes ubiquitination and degradation of p53, decreasing p53, p21, and Noxa levels, thereby facilitating hepatocellular carcinoma cell growth.	PMID:28935368	Biochemical and biophysical research communications
2022	Medium	UBE2T promotes K63-linked ubiquitination of Akt, activating Akt/β-catenin signaling; E2-enzyme-deficient mutation C86A of UBE2T and ubiquitination-site-deficient mutation K8/14R of Akt impair downstream pathway activation and pyrimidine enzyme upregulation in HCC.	PMID:35169125	Cell death & disease
2021	Medium	UBE2T physically binds the E3 ubiquitin ligase Mule and regulates its protein level via ubiquitination, thereby preventing Mule-mediated degradation of β-catenin and promoting liver CSC functions. This effect requires the E2 catalytic activity of UBE2T.	PMID:33542213	Cell death & disease
2021	Medium	NEDD4L is an E3 ligase that ubiquitinates UBE2T and targets it for proteasomal degradation, reducing UBE2T protein half-life; NEDD4L-mediated UBE2T degradation represses PI3K-AKT signaling and suppresses lung adenocarcinoma cell progression.	PMID:34838005	Cancer cell international
2020	Low	SENP1 deSUMOylates UBE2T, increasing UBE2T protein expression and activating the Akt pathway, promoting HCC progression. UBE2T is thus identified as a SUMOylation substrate regulated by SENP1.	PMID:31969492	Aging
2023	Medium	UBE2T catalyzes RING1-mediated ubiquitination of p53, relieving transcriptional repression of ribonucleotide reductase subunits RRM1 and RRM2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress in pancreatic cancer, conferring gemcitabine resistance.	PMID:36842710	Gastroenterology
2022	Low	UBE2T directly binds FANCI and regulates its monoubiquitination; overexpression of UBE2T reversed effects of FANCI knockdown in NSCLC cells, placing UBE2T upstream of FANCI monoubiquitination in a cancer context.	PMID:35703356	Oncology reports
2022	Low	UBE2T mediates K48-linked polyubiquitination and degradation of ribosomal protein L6 (RPL6) in an E3 ligase-independent manner in glioblastoma, reducing wild-type p53 and enhancing gain-of-function mutant p53.	PMID:36156329	Cancer science
2023	Medium	UBE2T resolves R-loops and stabilizes replication forks at transcription-replication conflict sites and common fragile sites in primordial germ cells (PGCs), and promotes mitotic DNA synthesis to maintain genome stability; Ube2t knockout mice show defects in PGC proliferation with DNA damage accumulation and p53 pathway activation.	PMID:36928776	Cellular and molecular life sciences
2019	Medium	CRISPR/Cas9-mediated knockout of UBE2T in HeLa and U2OS cells only partially reduced homologous recombination (HR), demonstrating that UBE2T-independent pathways can compensate for the recombination defect in UBE2T/FANCT null cells.	PMID:30715513	Nucleic acids research
2024	Medium	Fragment screening by 19F-NMR and 1H-15N-HSQC, validated by X-ray crystallography, identified two new binding pockets on UBE2T distinct from the active site; compounds binding these sites show inhibitory activity on UBE2T ubiquitination.	PMID:38358126	Protein science
2025	Medium	UBE2T mediates K48-linked polyubiquitination and proteasomal degradation of CDC42, thereby preventing CDC42-mediated autophagic lysosomal degradation of CD276 (B7-H3), leading to CD276 upregulation, impairment of CD8+ T cell function, and immune escape in triple-negative breast cancer.	PMID:39915000	Journal for immunotherapy of cancer
2024	Medium	UBE2T collaborates with E3 ligase TRIM25 to perform K48-linked polyubiquitination and degradation of CBX6 at K214, relieving transcriptional repression of pluripotency genes SOX2 and NANOG and enhancing breast cancer stem cell stemness.	PMID:39716485	Cancer letters
2025	Low	UBE2T mediates ubiquitination-dependent degradation of HP1α via the proteasome pathway in IDH1/TP53-mutant glioma, leading to release of suppressive effects of R-2-hydroxyglutarate on nucleolar function and increased rDNA transcription.	PMID:40627452	Clinical cancer research
2021	Low	UBE2T mediates ubiquitination of BIRC5 (survivin) through interaction with DEPDC1B in chordoma cells; simultaneous downregulation of BIRC5 and DEPDC1B exacerbates the inhibitory effects, and BIRC5 overexpression reverses the inhibitory effects of DEPDC1B knockdown.	PMID:34330893	Cell death & disease
2026	Low	Betulinic acid (BA) selectively suppresses UBE2T expression at the transcriptional level via MAPK/ERK pathway inhibition (pharmacological reactivation of ERK reverses UBE2T suppression), thereby blocking FANCL-UBE2T-mediated FANCI/FANCD2 monoubiquitination, impairing ICL repair, and sensitizing glioma to cisplatin.	PMID:41486508	Journal of cellular and molecular medicine
2025	Low	UBE2T cooperates with E3 ligase TRIM28 to facilitate K48-linked ubiquitination and degradation of phospho-GSK3β (pGSK3β), disrupting the β-catenin destruction complex and promoting nuclear translocation of β-catenin, thereby activating prostate cancer stem cell self-renewal.	PMID:42070337	Phytomedicine
2024	Low	UBE2T mediates ubiquitination of the transcription factor PBX1, which then affects transcriptional regulation of RORA in lung adenocarcinoma; luciferase reporter assay, ChIP, and Co-IP established the UBE2T–PBX1–RORA regulatory axis.	PMID:39289660	BMC cancer
2024	Low	UBE2T mediates ubiquitination and degradation of SORBS3, thereby enhancing IL-6/STAT3 signaling and promoting lung adenocarcinoma progression; validated in vitro and in vivo.	PMID:38816989	Journal of biochemical and molecular toxicology
2025	Low	UBE2T promotes papillary thyroid carcinoma progression by co-immunoprecipitating with SOCS2 and promoting its destabilization, thereby relieving SOCS2-mediated inhibition of STAT3 phosphorylation and activating JAK-STAT3 signaling.	PMID:41330207	Seminars in oncology

Citations

PMID:16916645
PMID:17938197
PMID:19111657
PMID:19589784
PMID:21722982
PMID:22615860
PMID:24389026
PMID:26046368
PMID:26085575
PMID:26119737
PMID:28437106
PMID:28933844
PMID:28935368
PMID:30715513
PMID:31481791
PMID:31525021
PMID:31969492
PMID:32590022
PMID:33087136
PMID:33323973
PMID:33542213
PMID:34330893
PMID:34838005
PMID:35169125
PMID:35703356
PMID:36156329
PMID:36842710
PMID:36928776
PMID:38358126
PMID:38816989
PMID:39289660
PMID:39716485
PMID:39915000
PMID:40627452
PMID:41330207
PMID:41486508
PMID:42070337

📚 Additional Documentation

Notes

(UBE2T-notes.md)

UBE2T (Q9NPD8) — gene review notes

Identity

UBE2T = Ubiquitin-conjugating enzyme E2 T (UBC family). AltNames: PIG50 (cell proliferation-inducing gene 50), HSPC150. HGNC:25009. 197 aa; UBC catalytic core (residues 2–152) with active-site Cys86; C-terminal disordered tail (149–197). EC 2.3.2.23.
Fanconi anemia complementation group T (FANCT / FA-T); biallelic loss causes FA.

Core biology (E2 of the Fanconi anemia pathway)

UBE2T is the ubiquitin-conjugating enzyme (E2) essential for the FA pathway; it binds the RING E3 ligase FANCL and is required for monoubiquitination of FANCD2 in vivo. UBE2T depletion → abnormal chromosomes (FA hallmark) after DNA damage PMID:16916645.
Active-site Cys86 is required for E2 activity: C86A abolishes activity (mutagenesis across PMID:16916645, 17938197, 19111657, 19589784, 19887602; UniProt MUTAGEN 86 "C->A: Loss of E2 enzyme activity").
FANCL–UBE2T is a strict, exclusive/cognate E3–E2 pair; FANCL selects UBE2T over other E2s via an extensive electrostatic/H-bond network beyond the conserved hydrophobic interface; Arg60 of UBE2T is the positive selector (salt bridge with Glu340 of FANCL) [PMID:24389026 "FANCL will preferentially select Ube2T"; "the positive selector in Ube2T for FANCL is Arg60, which forms a salt bridge with Glu340 of FANCL ... and is required for FANCL-Ube2T-mediated monoubiquitination of FANCD2"; "FANCL exclusively formed a complex with Ube2T"].
Minimal reconstitution: UBE2T + FANCL monoubiquitinate FANCD2; FANCL's RWD-like domain stimulates it; adding FANCI enhances and restricts modification to the physiological substrate lysine of FANCD2 PMID:19111657.
UBE2T–FANCL also monoubiquitinates FANCI on Lys-523 in vitro PMID:19589784.
Regulation is by localization, not complex assembly: UBE2T, the FA core complex, and FANCD2 are recruited independently to chromatin; an active E2/E3 holoenzyme forms transiently on chromatin. UBE2T is constitutively present in the chromatin compartment [PMID:17938197 "UBE2T and FANCD2 access this subcellular fraction independently of the FA core complex. FANCD2 monoubiquitination is therefore not regulated by multiprotein complex assembly but by the formation of an active E2/E3 holoenzyme on chromatin."; "The E2-conjugating enzyme UBE2T is constitutively present in this compartment."].

Localization

Nucleus (UniProt SUBCELLULAR LOCATION "Nucleus"; Note="Accumulates to chromatin"). Experimental nuclear localization PMID:19887602, TAS nucleus PMID:17938197. Reactome places it in nucleoplasm.

Disease (FANCT / FA-T)

Biallelic UBE2T mutations cause FA; the p.Gln2Glu variant abolishes FANCD2 monoubiquitination and interaction with FANCL; complementation group named FA-T PMID:26046368. UniProt VARIANT 2 (Q->E) in FANCT.

Autoregulation / autoubiquitination

UBE2T undergoes automonoubiquitination (Lys-91, also Lys-182); one report says this inactivates the E2 PMID:16916645, another finds no effect on activity (PMID:19111657). Regulatory/self-limiting, not the core catalytic output.

Other reported activities (context-dependent / in vitro)

Polyubiquitination of BRCA1 and its downregulation upon UBE2T overexpression in breast cancer cells; interacts/colocalizes with BRCA1/BARD1; requires active Cys86 PMID:19887602. This is an overexpression/cancer-cell context; not the canonical FA-pathway function.
In vitro (E3-free) assay of all human E2s: UBE2T can drive polyubiquitination through multiple ubiquitin lysines; UniProt summarizes "In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:20061386)." Source paper PMID:20061386 was performed in the ABSENCE of E3 ("this study was performed in the absence of an E3 enzyme"), so the six lysine-linkage-specific BP annotations reflect intrinsic in-vitro lysine preference, not the physiological (monoubiquitination) role → over-annotation of biological role.
GNB2 interaction (P62879) reported in a large-scale neurodegenerative-disease Y2H interactome PMID:32814053; also in UniProt INTERACTION. Non-core, generic protein binding.

Annotation review synthesis

CORE MF: ubiquitin conjugating enzyme (E2) activity GO:0061631.
CORE BP: FANCD2/FANCI monoubiquitination in interstrand cross-link repair (FA pathway) → protein monoubiquitination GO:0006513; interstrand cross-link repair GO:0036297; DNA damage response GO:0006974.
CORE CC: nucleus / nucleoplasm (functions on chromatin).
CORE partner interaction: FANCL (ubiquitin protein ligase binding GO:0031625).
Non-core: autoubiquitination (regulatory), polyubiquitination + lysine-linkage in-vitro capacities, BRCA1 downregulation (overexpression context), generic protein binding (FANCL redundant w/ GO:0031625; GNB2 HT screen).
GO:0004842 (ubiquitin-protein transferase activity) IDA x4 → MODIFY to the more specific E2 term GO:0061631.
GO:0006281 (DNA repair) IMP → MODIFY to GO:0036297 interstrand cross-link repair (MMC/ICL context).

📄 View Raw YAML

id: Q9NPD8
gene_symbol: UBE2T
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  UBE2T (ubiquitin-conjugating enzyme E2 T; also PIG50/HSPC150) is the E2
  ubiquitin-conjugating enzyme of the Fanconi anemia (FA) DNA interstrand
  cross-link repair pathway. It is a 197-residue member of the UBC family with a
  canonical ubiquitin-conjugating catalytic core and active-site Cys86 that forms
  the ubiquitin thioester intermediate. UBE2T pairs specifically and exclusively
  with the RING E3 ubiquitin ligase FANCL of the FA core complex, and this cognate
  E2/E3 holoenzyme catalyzes the site-specific monoubiquitination of FANCD2 (and of
  FANCI) — the central activating step of the FA pathway that promotes recruitment
  of downstream DNA repair factors to interstrand cross-links and stalled
  replication forks. FANCL selectivity for UBE2T is achieved through an extensive
  electrostatic/hydrogen-bond network beyond the generic hydrophobic E2/E3
  interface, with Arg60 of UBE2T acting as the key positive selector. Regulation of
  FANCD2 monoubiquitination occurs by DNA-damage-induced localization of the
  enzymes to chromatin rather than by assembly of the core complex; UBE2T is
  constitutively present in the nuclear/chromatin compartment. UBE2T also undergoes
  self-limiting automonoubiquitination (Lys-91/Lys-182) that has been reported to
  down-regulate its activity. Biallelic loss-of-function of UBE2T causes Fanconi
  anemia (complementation group FANCT/FA-T), a chromosomal-instability disorder
  with bone marrow failure, developmental malformations, and cancer predisposition.
  Additional activities reported outside the canonical pathway — polyubiquitination
  and downregulation of BRCA1 in overexpressing breast-cancer cells, and an
  intrinsic in-vitro ability (in the absence of an E3) to build polyubiquitin chains
  through several ubiquitin lysines — are context-specific or non-physiological.
existing_annotations:
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) annotation to protein polyubiquitination, a family-level
      capability of UBC E2s. UBE2T can drive polyubiquitination in vitro and
      polyubiquitinates BRCA1 in overexpression settings, but its physiological FA
      role is monoubiquitination of FANCD2/FANCI.
    action: KEEP_AS_NON_CORE
    reason: >-
      Not incorrect — UBE2T has demonstrable polyubiquitination capacity
      (PMID:20061386, PMID:19887602) — but polyubiquitination is not the core
      biological function of UBE2T, which is site-specific monoubiquitination in the
      FA pathway. Retained as a valid non-core annotation.
    supported_by:
    - reference_id: PMID:19887602
      supporting_text: >-
        BRCA1 to be polyubiquitinated by incubation with
- term:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) annotation to the core E2 ubiquitin-conjugating enzyme
      activity. This is the defining molecular function of UBE2T.
    action: ACCEPT
    reason: >-
      Well supported at both the family (IBA) and gene-specific experimental levels.
      UBE2T is the E2 essential for the FA pathway, accepting ubiquitin from E1 and,
      with FANCL, transferring it to FANCD2/FANCI. This is the correctly specific MF
      term for an E2 and represents the core function.
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) annotation placing UBE2T in the DNA damage response,
      consistent with its role in the FA pathway triggered by replication-blocking
      DNA lesions.
    action: ACCEPT
    reason: >-
      Consistent with experimental evidence: UBE2T-catalyzed FANCD2 monoubiquitination
      is a DNA-damage/S-phase-restricted event and UBE2T depletion produces the
      DNA-damage-associated chromosomal abnormalities of FA.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        The Fanconi anemia (FA) nuclear core complex and the E2 ubiquitin-conjugating
        enzyme UBE2T are required for the S phase and DNA damage-restricted
        monoubiquitination of FANCD2.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic annotation (from UniProt subcellular-location mapping) to nucleus,
      matching the UniProt SUBCELLULAR LOCATION and experimental data.
    action: ACCEPT
    reason: >-
      UBE2T is a nuclear protein that accumulates on chromatin; the nuclear location
      is experimentally established and is where UBE2T functions in the FA pathway.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        UBE2T and FANCD2 access this subcellular fraction independently of the FA core
        complex.
- term:
    id: GO:0019787
    label: ubiquitin-like protein transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA) annotation to a broad parent molecular-function term
      encompassing ubiquitin/UBL transfer.
    action: ACCEPT
    reason: >-
      Correct but less specific than the E2-specific GO:0061631 that is also
      annotated. A broader electronic term is acceptable; no change needed, though it
      is not the most informative representation of UBE2T's activity.
- term:
    id: GO:0032446
    label: protein modification by small protein conjugation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation to a broad parent process for ubiquitin/UBL
      conjugation.
    action: ACCEPT
    reason: >-
      A correct high-level process term consistent with UBE2T's ubiquitin-conjugating
      role. Broader than the specific monoubiquitination/ICL-repair processes but not
      wrong; acceptable as a general electronic annotation.
- term:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      Electronic annotation from EC 2.3.2.23 mapping to E2 ubiquitin-conjugating
      enzyme activity — the core molecular function of UBE2T.
    action: ACCEPT
    reason: >-
      EC 2.3.2.23 is assigned to UBE2T with experimental support (PMID:20061386) and
      maps correctly to the E2 activity term, which is also supported experimentally
      and phylogenetically. Core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24389026
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation from the FANCL RING–UBE2T structure
      (interactor FANCL, Q9NW38). This physical interaction is central to UBE2T
      function but is captured uninformatively here.
    action: KEEP_AS_NON_CORE
    reason: >-
      The FANCL interaction is real and important, but 'protein binding' (GO:0005515)
      is uninformative; the same interaction is better represented by the
      ubiquitin-protein-ligase-binding annotations (GO:0031625). Retained as valid
      but non-core; the informative term is preferred for core representation.
    supported_by:
    - reference_id: PMID:24389026
      supporting_text: >-
        FANCL exclusively formed a complex with Ube2T
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation to GNB2 (P62879) from a large-scale
      neurodegenerative-disease yeast two-hybrid interactome.
    action: KEEP_AS_NON_CORE
    reason: >-
      A high-throughput binary interaction of unclear biological significance for
      UBE2T's function; also recorded in UniProt INTERACTION. Generic 'protein
      binding' is uninformative. Retained as non-core rather than removed, since the
      interaction is documented.
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation (UniPathway mapping) to the general protein
      ubiquitination process.
    action: ACCEPT
    reason: >-
      A correct broad process term for an E2 ubiquitin-conjugating enzyme. Broader
      than the specific monoubiquitination role but accurate; acceptable as a general
      electronic annotation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:19887602
  qualifier: located_in
  review:
    summary: >-
      Experimental nuclear localization of UBE2T in breast cancer cells.
    action: ACCEPT
    reason: >-
      Direct experimental support for the nuclear localization that is consistent
      with UBE2T's function; matches UniProt SUBCELLULAR LOCATION 'Nucleus'.
    supported_by:
    - reference_id: PMID:19887602
      supporting_text: >-
        UBE2T interacted and colocalized with the BRCA1/BRCA1-associated RING domain
        protein (BARD1) complex.
- term:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  evidence_type: EXP
  original_reference_id: PMID:20061386
  qualifier: enables
  review:
    summary: >-
      Experimental demonstration of UBE2T E2 ubiquitin-conjugating enzyme activity
      (catalytic activity underlying EC 2.3.2.23).
    action: ACCEPT
    reason: >-
      David et al. purified and assayed UBE2T among all human E2s, confirming its E2
      conjugating activity. Core molecular function.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        the E2 enzymes are capable of directing the ubiquitination process to distinct
        subsets of ubiquitin lysines, depending on the specific E2 utilized
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8852130
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) nucleoplasm location, from the reaction in which E1 (UBA1)
      charges nuclear E2 enzymes with ubiquitin.
    action: ACCEPT
    reason: >-
      Nucleoplasm is a valid, appropriately specific nuclear location for UBE2T,
      consistent with its nuclear/chromatin localization and its function there in the
      FA pathway.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785361
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) nucleoplasm location, from the FANCD2:FANCI monoubiquitination
      reaction of the FA pathway.
    action: ACCEPT
    reason: >-
      Consistent with UBE2T functioning in the nucleus/on chromatin during FANCD2/FANCI
      monoubiquitination. Valid location annotation.
- term:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  evidence_type: IDA
  original_reference_id: PMID:19589784
  qualifier: enables
  review:
    summary: >-
      Direct assay (IDA) of UBE2T E2 activity: the UBE2T-FANCL pair monoubiquitinates
      FANCI on Lys-523 in vitro.
    action: ACCEPT
    reason: >-
      Direct experimental support for UBE2T's E2 conjugating enzyme activity in the FA
      pathway context. Core molecular function.
    supported_by:
    - reference_id: PMID:19589784
      supporting_text: >-
        FANCI can be ubiquitinated on Lys-523 by the UBE2T-FANCL pair in vitro
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785342
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) nucleoplasm location, from the reaction in which the
      FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex.
    action: ACCEPT
    reason: >-
      Valid nuclear location consistent with UBE2T acting at ICL-DNA/chromatin within
      the FA pathway.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788385
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) nucleoplasm location, associated with FA-pathway reactions at
      ICL-DNA.
    action: ACCEPT
    reason: >-
      Valid, appropriately specific nuclear location for UBE2T consistent with its
      site of action.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788392
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) nucleoplasm location, associated with FA-pathway reactions at
      ICL-DNA.
    action: ACCEPT
    reason: >-
      Valid nuclear location consistent with UBE2T's nuclear/chromatin function in the
      FA pathway.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:17938197
  qualifier: enables
  review:
    summary: >-
      IDA chromatin-binding annotation reflecting UBE2T's constitutive presence in and
      accumulation on the chromatin fraction, where it forms the active E2/E3
      holoenzyme with FANCL.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported chromatin association (UBE2T is constitutively present
      in the chromatin compartment and FANCD2 monoubiquitination is regulated by
      localization to chromatin). This localization/binding supports but is not itself
      the core catalytic function; retained as non-core.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        The E2-conjugating enzyme UBE2T is constitutively present in this compartment.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:16916645
  qualifier: enables
  review:
    summary: >-
      IDA annotation to the general ubiquitin-protein transferase activity term based
      on UBE2T's demonstrated role as the E2 that transfers ubiquitin to FANCD2.
    action: MODIFY
    reason: >-
      Correct in essence but not the most specific/informative term. UBE2T is an E2
      ubiquitin-conjugating enzyme; the E2-specific molecular function
      GO:0061631 (ubiquitin conjugating enzyme activity) better represents its
      activity than the broader GO:0004842 (which also covers E3 ligase activity).
    proposed_replacement_terms:
    - id: GO:0061631
      label: ubiquitin conjugating enzyme activity
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:17938197
  qualifier: enables
  review:
    summary: >-
      IDA annotation to the general ubiquitin-protein transferase activity term from
      the reconstituted FANCD2 monoubiquitination system.
    action: MODIFY
    reason: >-
      As above, the E2-specific term GO:0061631 is the more accurate/informative
      molecular function for UBE2T than the broader GO:0004842.
    proposed_replacement_terms:
    - id: GO:0061631
      label: ubiquitin conjugating enzyme activity
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        the E2 ubiquitin-conjugating enzyme UBE2T are required for the S phase and DNA
        damage-restricted monoubiquitination of FANCD2
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:19111657
  qualifier: enables
  review:
    summary: >-
      IDA annotation to general ubiquitin-protein transferase activity from the
      minimal Ube2t/FANCL FANCD2 monoubiquitination reconstitution.
    action: MODIFY
    reason: >-
      Essence is correct but the E2-specific GO:0061631 is the more precise molecular
      function term for UBE2T.
    proposed_replacement_terms:
    - id: GO:0061631
      label: ubiquitin conjugating enzyme activity
    supported_by:
    - reference_id: PMID:19111657
      supporting_text: >-
        we minimally reconstitute this monoubiquitination reaction with Ube2t and the
        FANCL protein
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:17938197
  qualifier: located_in
  review:
    summary: >-
      TAS nuclear localization annotation, consistent with experimental and
      UniProt-curated nuclear localization.
    action: ACCEPT
    reason: >-
      UBE2T is nuclear and functions there in the FA pathway; the nuclear location is
      well established.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        UBE2T and FANCD2 access this subcellular fraction independently of the FA core
        complex.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IMP
  original_reference_id: PMID:16916645
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation to DNA repair: UBE2T depletion impairs mitomycin-C-induced repair
      and produces the chromosomal abnormalities characteristic of FA.
    action: MODIFY
    reason: >-
      Correct but too general. UBE2T's function is specifically in the Fanconi anemia
      DNA interstrand cross-link (ICL) repair pathway (the IMP evidence uses
      mitomycin C, an ICL-inducing agent). The more specific process term
      GO:0036297 (interstrand cross-link repair) better represents this role.
    proposed_replacement_terms:
    - id: GO:0036297
      label: interstrand cross-link repair
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        DNA damage in UBE2T-depleted cells leads to the formation of abnormal
        chromosomes that are a hallmark of Fanconi anemia.
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16916645
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to protein monoubiquitination — the central FA-pathway activity
      of UBE2T (monoubiquitination of FANCD2, required in vivo).
    action: ACCEPT
    reason: >-
      Directly supported and represents the core biological process catalyzed by
      UBE2T with FANCL: site-specific monoubiquitination of FANCD2.
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        is required for the monoubiquitination of FANCD2 in vivo
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:17938197
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to protein monoubiquitination from the study establishing that
      FANCD2 monoubiquitination requires UBE2T and is regulated by chromatin
      localization.
    action: ACCEPT
    reason: >-
      Core biological process; directly supported by the requirement of UBE2T for
      DNA-damage-restricted FANCD2 monoubiquitination.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        FANCD2 monoubiquitination is therefore not regulated by multiprotein complex
        assembly but by the formation of an active E2/E3 holoenzyme on chromatin.
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:19111657
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to protein monoubiquitination from the minimal reconstitution
      showing FANCI restricts the modification to the physiological FANCD2 substrate
      lysine.
    action: ACCEPT
    reason: >-
      Core biological process directly catalyzed by UBE2T with FANCL (site-specific
      FANCD2 monoubiquitination).
    supported_by:
    - reference_id: PMID:19111657
      supporting_text: >-
        addition of the FANCI protein enhances monoubiquitination and also restricts it
        to the in vivo substrate lysine residue on FANCD2
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IMP
  original_reference_id: PMID:16916645
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation to DNA damage response, from loss-of-function evidence linking
      UBE2T to the DNA-damage-activated FA pathway.
    action: ACCEPT
    reason: >-
      UBE2T operates in the DNA-damage/replication-stress-activated FA pathway; its
      depletion produces the DNA-damage-induced chromosomal instability of FA.
      Consistent with the IBA DNA damage response annotation.
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        The Fanconi anemia pathway is required for the efficient repair of damaged DNA.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:16916645
  qualifier: enables
  review:
    summary: >-
      IPI annotation for binding the E3 ubiquitin-protein ligase FANCL (Q9NW38), the
      cognate partner of UBE2T in the FA pathway.
    action: ACCEPT
    reason: >-
      Informative and central: the UBE2T-FANCL E2-E3 interaction is required for FANCD2
      monoubiquitination. FANCL is the RING E3 ligase subunit of the FA core complex.
      This is the informative counterpart to the generic 'protein binding' annotation.
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        UBE2T binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core
        complex
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:17938197
  qualifier: enables
  review:
    summary: >-
      IPI annotation for UBE2T binding the E3 ligase FANCL, forming the active E2/E3
      holoenzyme on chromatin.
    action: ACCEPT
    reason: >-
      Supported and functionally central; the FANCL interaction underlies UBE2T's role
      in FANCD2 monoubiquitination.
    supported_by:
    - reference_id: PMID:17938197
      supporting_text: >-
        the formation of an active E2/E3 holoenzyme on chromatin
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:19111657
  qualifier: enables
  review:
    summary: >-
      IPI annotation for UBE2T-FANCL binding; the FANCL RWD-like domain stimulates the
      UBE2T-catalyzed reaction.
    action: ACCEPT
    reason: >-
      Directly supported and central to function; FANCL binding is required for
      efficient FANCD2 monoubiquitination.
    supported_by:
    - reference_id: PMID:19111657
      supporting_text: >-
        monoubiquitination is stimulated by a conserved RWD-like domain in FANCL
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:16916645
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to protein autoubiquitination: UBE2T undergoes
      automonoubiquitination (Lys-91), stimulated by FANCL, reported to inactivate the
      enzyme.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported but a regulatory/self-limiting modification rather than
      UBE2T's core catalytic output (FANCD2/FANCI monoubiquitination). The functional
      consequence is also disputed between reports (PMID:16916645 inactivating;
      PMID:19111657 no effect). Retained as non-core.
    supported_by:
    - reference_id: PMID:16916645
      supporting_text: >-
        UBE2T undergoes automonoubiquitination in vivo. This monoubiquitination is
        stimulated by the presence of the FANCL protein and inactivates UBE2T.
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:19111657
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to protein autoubiquitination (Lys-91/Lys-182) from the
      mechanistic reconstitution study.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supported but regulatory and non-core; here autoubiquitination was reported not
      to affect E2 activity, underscoring that it is a modulatory feature rather than
      the enzyme's core function.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: enables
  review:
    summary: >-
      IDA annotation to general ubiquitin-protein transferase activity from the
      systematic in-vitro characterization of all human E2 enzymes.
    action: MODIFY
    reason: >-
      Correct but too general; the E2-specific GO:0061631 (ubiquitin conjugating
      enzyme activity) more precisely captures UBE2T's molecular function.
    proposed_replacement_terms:
    - id: GO:0061631
      label: ubiquitin conjugating enzyme activity
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        the E2 enzymes are capable of directing the ubiquitination process to distinct
        subsets of ubiquitin lysines, depending on the specific E2 utilized
- term:
    id: GO:0035519
    label: protein K29-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K29-linked ubiquitination from an in-vitro, E3-free assay of
      intrinsic E2 lysine preference.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Derived from a systematic in-vitro study performed in the absence of an E3
      ligase, measuring the intrinsic lysine preferences of purified E2s. This does not
      reflect UBE2T's physiological function (site-specific monoubiquitination of
      FANCD2/FANCI with FANCL); UniProt notes the all-seven-lysine polyubiquitination is
      an in-vitro capacity. Over-annotation of the biological role.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
- term:
    id: GO:0044314
    label: protein K27-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K27-linked ubiquitination from the in-vitro, E3-free E2
      lysine-preference assay.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      In-vitro capacity measured without an E3 ligase; not representative of UBE2T's
      physiological monoubiquitination role in the FA pathway. Over-annotation.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
- term:
    id: GO:0070534
    label: protein K63-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K63-linked ubiquitination from the in-vitro, E3-free E2
      lysine-preference assay.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Reflects intrinsic in-vitro lysine preference measured without an E3; not the
      physiological FA-pathway function of UBE2T. Over-annotation of biological role.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
- term:
    id: GO:0070936
    label: protein K48-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K48-linked ubiquitination from the in-vitro, E3-free E2
      lysine-preference assay.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      In-vitro capacity determined in the absence of an E3 ligase; does not represent
      UBE2T's physiological function. Over-annotation of biological role.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
- term:
    id: GO:0070979
    label: protein K11-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K11-linked ubiquitination from the in-vitro, E3-free E2
      lysine-preference assay.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Intrinsic in-vitro lysine preference measured without an E3; not the physiological
      monoubiquitination role of UBE2T. Over-annotation of biological role.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
- term:
    id: GO:0085020
    label: protein K6-linked ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:20061386
  qualifier: involved_in
  review:
    summary: >-
      IDA annotation to K6-linked ubiquitination from the in-vitro, E3-free E2
      lysine-preference assay.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Reflects intrinsic in-vitro lysine usage measured without an E3 ligase; not
      representative of UBE2T's physiological FA-pathway function. Over-annotation.
    supported_by:
    - reference_id: PMID:20061386
      supporting_text: >-
        Because this study was performed in the absence of an E3 enzyme, our data
        indicate that the E2 enzymes are capable of directing the ubiquitination process
        to distinct subsets of ubiquitin lysines
core_functions:
- description: >-
    E2 ubiquitin-conjugating enzyme of the Fanconi anemia pathway: accepts ubiquitin
    from the E1 activating enzyme via active-site Cys86 and, partnered with the
    cognate RING E3 ligase FANCL, catalyzes the DNA-damage-induced, site-specific
    monoubiquitination of FANCD2 (and FANCI) on chromatin, the central activating
    step of interstrand cross-link repair.
  supported_by:
  - reference_id: PMID:16916645
    supporting_text: >-
      UBE2T is the ubiquitin-conjugating enzyme (E2) essential for this pathway. UBE2T
      binds to FANCL, the ubiquitin ligase subunit of the Fanconi anemia core complex,
      and is required for the monoubiquitination of FANCD2 in vivo.
  - reference_id: PMID:19111657
    supporting_text: >-
      addition of the FANCI protein enhances monoubiquitination and also restricts it
      to the in vivo substrate lysine residue on FANCD2
  molecular_function:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  directly_involved_in:
  - id: GO:0006513
    label: protein monoubiquitination
  - id: GO:0036297
    label: interstrand cross-link repair
  - id: GO:0006974
    label: DNA damage response
  locations:
  - id: GO:0005654
    label: nucleoplasm
references:
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:16916645
  title: UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Foundational paper establishing UBE2T as the E2 of the FA pathway: binds FANCL,
      required for FANCD2 monoubiquitination in vivo, depletion causes FA-like
      chromosomal abnormalities, and undergoes inactivating automonoubiquitination.
      Abstract verified against PubMed; supporting quotes are verbatim from the cached
      abstract.
- id: PMID:17938197
  title: 'UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently
    to chromatin: a basis for the regulation of FANCD2 monoubiquitination.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes that FANCD2 monoubiquitination is regulated by DNA-damage-induced
      chromatin localization of an active E2/E3 holoenzyme rather than by core-complex
      assembly, and that UBE2T is constitutively present in the chromatin compartment.
      Full text available and quotes verified verbatim.
- id: PMID:19111657
  title: Mechanistic insight into site-restricted monoubiquitination of FANCD2 by
    Ube2t, FANCL, and FANCI.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Minimal reconstitution of FANCD2 monoubiquitination with Ube2t + FANCL; FANCL
      RWD-like domain stimulates the reaction and FANCI restricts it to the
      physiological substrate lysine. Also maps autoubiquitination sites (Lys-91/182).
      Abstract quotes verified verbatim.
- id: PMID:19589784
  title: FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates in-vitro monoubiquitination of FANCI on Lys-523 by the UBE2T-FANCL
      pair, extending UBE2T's substrate set beyond FANCD2. Full text available; quote
      verified verbatim.
- id: PMID:19887602
  title: Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme
    E2T overexpression in human breast cancer cells.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reports UBE2T overexpression-driven BRCA1 polyubiquitination/downregulation and
      interaction with BRCA1/BARD1 in breast cancer cells; Cys86-dependent. A
      context-specific (overexpression/cancer) activity, not the canonical FA-pathway
      function. Abstract verified.
- id: PMID:20061386
  title: The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred
    lysines.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Systematic in-vitro survey of all human E2s in the ABSENCE of E3, assigning
      intrinsic lysine preferences; source of the K6/K11/K27/K29/K48/K63 linkage
      annotations for UBE2T. Confirms UBE2T E2 activity but the linkage-specific
      polyubiquitination reflects in-vitro capacity, not physiological function. Full
      text (cached extract) truncated at the introduction; abstract quotes verified
      verbatim.
- id: PMID:24389026
  title: Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate
    E3-E2 selection.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Crystal structure of the FANCL RING-Ube2T complex; defines the exclusive,
      cognate E3-E2 pairing and identifies Arg60 of UBE2T as the positive selector for
      FANCL. Full text available; quotes verified verbatim. Also the source of the
      FANCL IPI 'protein binding' annotation.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale neurodegenerative-disease Y2H interactome; source of the UBE2T-GNB2
      binary interaction underlying a generic 'protein binding' annotation. Interaction
      of unclear functional significance for UBE2T; correctly cited but low relevance
      to the gene's core function.
- id: PMID:26046368
  title: Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi
    anemia.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the gene-disease link (Fanconi anemia complementation group FA-T):
      biallelic UBE2T mutations, p.Gln2Glu abolishing FANCD2 monoubiquitination and
      FANCL interaction. Not in GOA but central to interpreting UBE2T's biology; cited
      in the description. Abstract verified.
- id: Reactome:R-HSA-6785342
  title: FANCD2:FANCI complex and UBE2T bind ICL-DNA associated with the FA core complex
  findings: []
- id: Reactome:R-HSA-6785361
  title: Monoubiquitination of FANCD2:FANCI
  findings: []
- id: Reactome:R-HSA-6788385
  title: The complex of ATR and ATRIP is recruited to ICL-DNA
  findings: []
- id: Reactome:R-HSA-6788392
  title: ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA
  findings: []
- id: Reactome:R-HSA-8852130
  title: UBA1 conjugates ubiquitin to nuclear E2 enzymes
  findings: []

UBE2T

Gene Description