Tbio TRIP12 E3 ubiquitin-protein ligase TRIP12

Protein Summary

Description

E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]

Uniprot Accession IDs

• Q14669
• D4HL82
• Q14CA3
• Q14CF1
• Q15644
• Q53R87
• Q53TE7

Gene Name

• TRIP12

Ensembl ID

• ENST00000283943
• ENSP00000283943
• ENSG00000153827
• ENST00000389044
• ENSP00000373696
• ENST00000389045
• ENSP00000373697

Symbol

• KIAA0045
• ULF
• ULF
• MRD49
• TRIP-12

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
virus perturbation	1
interacting protein	0.89
disease perturbation	0.87
transcription factor binding site profile	0.85

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36.63   (req: < 5)

Gene RIFs: 16   (req: <= 3)

Antibodies: 65   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36.63   (req: >= 5)

Gene RIFs: 16   (req: > 3)

Antibodies: 65   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Expression Data (0 Tissues)

tutorial

No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

Go To Tool

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

Go To Tool

Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (512)

Explore Interacting Targets

1 – 10 of 512

• See Interactions on String-DB

CAPN1

Tchem

Novelty:  0.00252811

p_int:  0.999999986

p_ni:  1.4e-8

Score:  0.216

Data Source:  BioPlex,STRINGDB

UBE2D4

Tbio

Novelty:  0.40836104

p_int:  0.999999835

p_ni:  1.66e-7

Score:  0.965

Data Source:  BioPlex,STRINGDB

UBE2D1

Tbio

Novelty:  0.00865867

p_int:  0.999993437

p_ni:  0.000006563

Score:  0.978

Data Source:  BioPlex,STRINGDB

KBTBD7

Tdark

Novelty:  0.4947466

p_int:  0.996352639

p_ni:  0.003645749

p_wrong:  0.000001612

Score:  0.908

Data Source:  BioPlex,STRINGDB

EIF3I

Tbio

Novelty:  0.04398155

p_int:  0.99424745

p_ni:  0.00575254

p_wrong:  1e-8

Score:  0.185

Data Source:  BioPlex,STRINGDB

MECP2

Tchem

Family:  TF

Novelty:  0.00051767

p_int:  0.981862312

p_ni:  0.018137686

p_wrong:  2e-9

Data Source:  BioPlex

BCAT1

Tchem

Family:  Enzyme

Novelty:  0.00616446

p_int:  0.975142692

p_ni:  0.017851476

p_wrong:  0.007005833

Score:  0.212

Data Source:  BioPlex,STRINGDB

RP2

Tbio

Novelty:  0.12345247

p_int:  0.972349503

p_ni:  0.024086742

p_wrong:  0.003563755

Score:  0.181

Data Source:  BioPlex,STRINGDB

CYTH4

Tbio

Novelty:  0.05783135

p_int:  0.960085088

p_ni:  0.039914671

p_wrong:  2.41e-7

Data Source:  BioPlex

OPCML

Tbio

Novelty:  0.01569352

p_int:  0.957055449

p_ni:  0.029848371

p_wrong:  0.01309618

Score:  0.254

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (6)

Reactome (4)

KEGG (1)

UniProt (1)

Adaptive Immune System (R-HSA-1280218)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Reactome	Immune System	2246 targets	R-HSA-168256

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Immune System	2246 targets	R-HSA-168256

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (13)

Functions (2)

Components (4)

Processes (7)

Find Similar Targets

Items per page:

10

1 – 2 of 2

GO Term	Evidence	Assigned by
thyroid hormone receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin-protein transferase activity	Inferred from Direct Assay (IDA)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2	1	2		68.6
body height	EFO_0004339	1	1	1		56.4
systolic blood pressure	EFO_0006335	1	1	1		46.5
waist-hip ratio	EFO_0004343	1	1	1		42.3
glomerular filtration rate	EFO_0005208	2	2	1	5.9	31.1

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2		68.6
body height	EFO_0004339	1		56.4
systolic blood pressure	EFO_0006335	1		46.5
waist-hip ratio	EFO_0004343	1		42.3
glomerular filtration rate	EFO_0005208	1	5.9	31.1

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
Acetylation
Alternative splicing
Autism spectrum disorder
Complete proteome
Disease mutation
DNA damage
DNA repair
Mental retardation
Nucleus
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
body height
body mass index
glomerular filtration rate
grip strength measurement
systolic blood pressure
visceral adipose tissue measurement
waist-hip ratio

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
embryo phenotype
growth/size/body region phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	thyroid hormone receptor interactor 12	VGNC:2894	459994
Mouse	thyroid hormone receptor interactor 12	MGI:1309481	14897
Rat	thyroid hormone receptor interactor 12	RGD:1306607	316575
Dog	thyroid hormone receptor interactor 12	VGNC:47845	477400
Horse	thyroid hormone receptor interactor 12	VGNC:49287	100056934

Species	Name	OMA	EggNOG	Inparanoid
Chimp	thyroid hormone receptor interactor 12
Mouse	thyroid hormone receptor interactor 12
Rat	thyroid hormone receptor interactor 12
Dog	thyroid hormone receptor interactor 12
Horse	thyroid hormone receptor interactor 12

Publication Statistics

PubMed Score 36.63

PubMed score by year

Reset Zoom

PubTator Score 21.26

PubTator score by year

Reset Zoom

Related Publications

Text Mined References (33)

GeneRif Annotations (16)

Items per page:

10

0 of 0

PMID	Year	Title