Q9NPD8 · UBE2T_HUMAN
- ProteinUbiquitin-conjugating enzyme E2 T
- GeneUBE2T
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids197 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784, PubMed:28437106).
Also mediates monoubiquitination of FANCL and FANCI (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784).
May contribute to ubiquitination and degradation of BRCA1 (PubMed:19887602).
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).
Also mediates monoubiquitination of FANCL and FANCI (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784).
May contribute to ubiquitination and degradation of BRCA1 (PubMed:19887602).
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).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 86 | Glycyl thioester intermediate | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | chromatin binding | |
Molecular Function | ubiquitin conjugating enzyme activity | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | DNA damage response | |
Biological Process | DNA repair | |
Biological Process | protein autoubiquitination | |
Biological Process | protein K11-linked ubiquitination | |
Biological Process | protein K27-linked ubiquitination | |
Biological Process | protein K29-linked ubiquitination | |
Biological Process | protein K48-linked ubiquitination | |
Biological Process | protein K6-linked ubiquitination | |
Biological Process | protein K63-linked ubiquitination | |
Biological Process | protein monoubiquitination | |
Biological Process | protein polyubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Site-specific monoubiquitination of FANCD2 and FANCI. Basic triad in UBE2T active site interacts with acidic patch on FANCD2 for ubiquitination. Allosteric gating-effector couple in UBE2T regulates activation by FANCL.
Names & Taxonomy
Protein names
- Recommended nameUbiquitin-conjugating enzyme E2 T
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NPD8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Fanconi anemia complementation group T (FANCT)
- Note
- DescriptionA disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
- See alsoMIM:616435
Natural variants in FANCT
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_073861 | 2 | Q>E | in FANCT; abolishes FANCD2 monoubiquitination; abolishes interaction with FANCL; dbSNP:rs774357609 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_073861 | 2 | in FANCT; abolishes FANCD2 monoubiquitination; abolishes interaction with FANCL; dbSNP:rs774357609 | |||
Sequence: Q → E | ||||||
Mutagenesis | 5 | No effect on FANCL-binding, nor on FANCL-dependent monoubiquitination of FANCD2. | ||||
Sequence: S → R | ||||||
Mutagenesis | 60 | Loss of FANCL-binding and of FANCL-dependent monoubiquitination of FANCD2. | ||||
Sequence: R → E | ||||||
Mutagenesis | 63 | Decreased binding to FANCL. | ||||
Sequence: F → A | ||||||
Mutagenesis | 73 | Decreased FANCD2 ubiquitination. | ||||
Sequence: P → K | ||||||
Mutagenesis | 86 | Loss of E2 enzyme activity. | ||||
Sequence: C → A | ||||||
Mutagenesis | 91 | Decreased monoubiquitination. | ||||
Sequence: K → R | ||||||
Mutagenesis | 99-101 | No effect on FANCL-binding, nor on FANCL-dependent monoubiquitination of FANCD2. | ||||
Sequence: RPS → SPR | ||||||
Mutagenesis | 182-191 | Decreased monoubiquitination. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 207 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000082509 | 1-197 | UniProt | Ubiquitin-conjugating enzyme E2 T | |||
Sequence: MQRASRLKRELHMLATEPPPGITCWQDKDQMDDLRAQILGGANTPYEKGVFKLEVIIPERYPFEPPQIRFLTPIYHPNIDSAGRICLDVLKLPPKGAWRPSLNIATVLTSIQLLMSEPNPDDPLMADISSEFKYNKPAFLKNARQWTEKHARQKQKADEEEMLDNLPEAGDSRVHNSTQKRKASQLVGIEKKFHPDV | |||||||
Cross-link | 91 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 182 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 184 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 184 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 191 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 192 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
Auto-ubiquitinated. Effects of auto-monoubiquitination at Lys-91 and Lys-182 are unclear: according to a report, monoubiquitination inactivates E2 enzyme activity (PubMed:16916645).
In contrast, according to another report, autoubiquitination does not affect E2 enzyme activity (PubMed:19111657).
In contrast, according to another report, autoubiquitination does not affect E2 enzyme activity (PubMed:19111657).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Down-regulated following hypoxia. Up-regulated in breast cancers.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Directly interacts with FANCL (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:21775430, PubMed:24389026).
Interacts with BRCA1 (PubMed:19887602).
Interacts with BRCA1 (PubMed:19887602).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NPD8 | FANCL Q9NW38-1 | 3 | EBI-2130165, EBI-16088720 | |
BINARY | Q9NPD8 | GNB2 P62879 | 3 | EBI-2130165, EBI-356942 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-152 | UBC core | ||||
Sequence: QRASRLKRELHMLATEPPPGITCWQDKDQMDDLRAQILGGANTPYEKGVFKLEVIIPERYPFEPPQIRFLTPIYHPNIDSAGRICLDVLKLPPKGAWRPSLNIATVLTSIQLLMSEPNPDDPLMADISSEFKYNKPAFLKNARQWTEKHAR | ||||||
Compositional bias | 149-178 | Basic and acidic residues | ||||
Sequence: KHARQKQKADEEEMLDNLPEAGDSRVHNST | ||||||
Region | 149-197 | Disordered | ||||
Sequence: KHARQKQKADEEEMLDNLPEAGDSRVHNSTQKRKASQLVGIEKKFHPDV |
Sequence similarities
Belongs to the ubiquitin-conjugating enzyme family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length197
- Mass (Da)22,521
- Last updated2000-10-01 v1
- Checksum6C02D774A7FA928A
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8Y812 | A0A2R8Y812_HUMAN | UBE2T | 47 | ||
A0A8V8TPM9 | A0A8V8TPM9_HUMAN | UBE2T | 84 | ||
A0A8V8TQ15 | A0A8V8TQ15_HUMAN | UBE2T | 157 | ||
A0A8V8TN93 | A0A8V8TN93_HUMAN | UBE2T | 194 | ||
A0A8V8TNE2 | A0A8V8TNE2_HUMAN | UBE2T | 164 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 149-178 | Basic and acidic residues | ||||
Sequence: KHARQKQKADEEEMLDNLPEAGDSRVHNST |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB032931 EMBL· GenBank· DDBJ | BAA93711.1 EMBL· GenBank· DDBJ | mRNA | ||
AF160215 EMBL· GenBank· DDBJ | AAF67016.1 EMBL· GenBank· DDBJ | mRNA | ||
AF161499 EMBL· GenBank· DDBJ | AAF29114.1 EMBL· GenBank· DDBJ | mRNA | ||
AK000504 EMBL· GenBank· DDBJ | BAA91211.1 EMBL· GenBank· DDBJ | mRNA | ||
AY542309 EMBL· GenBank· DDBJ | AAT08178.1 EMBL· GenBank· DDBJ | mRNA | ||
AL356953 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471067 EMBL· GenBank· DDBJ | EAW91411.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC004152 EMBL· GenBank· DDBJ | AAH04152.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019284 EMBL· GenBank· DDBJ | AAH19284.1 EMBL· GenBank· DDBJ | mRNA |