TRAIP

Chr 3p21.31

TRAF interacting protein

Aliases:: TRIP, RNF206
MANE:: ENST00000331456.7

OMIM: 605958 ↗NCBI: 10293 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

TRAIP · Q9BWF2

v62025-08-01

Predicted Aligned Error matrix for TRAIP — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

74.9/ 100

Confident

469 residues

Confidence breakdown

Very high(≥ 90)47%
Confident(70–90)14%
Low(50–70)16%
Very low(< 50)24%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Seckel syndrome 9
0.66
Seckel syndrome
0.66
neurodegenerative disease
0.54
microcephalic primordial dwarfism
0.47
isolated growth hormone deficiency type IA
0.46
Fanconi anemia complementation group Q
0.37
uveal melanoma
0.23
hereditary disease
0.19
intelligence
0.09
major depressive disorder
0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

E3 ubiquitin-protein ligase TRAIP

E3 ubiquitin ligase required to protect genome stability in response to replication stress (PubMed:25335891, PubMed:26595769, PubMed:26711499, PubMed:26781088, PubMed:27462463, PubMed:31545170). Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription (By similarity). Controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of MCM7 subunit of the CMG helicase complex (By similarity). Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3 (By similarity). If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair pathway (By similarity). Only catalyzes ubiquitination of MCM7 when forks converge (By similarity). Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome (By similarity). Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys-63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity (PubMed:24553286). The function in translesion synthesis is however controversial (PubMed:26595769). Acts as a regulator of the spindle assembly checkpoint (PubMed:25335891). Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF (PubMed:22945920). Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation (PubMed:22945920)