TRAIP

This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis. [provided by RefSeq]

Full Name

TRAF interacting protein

Function

E3 ubiquitin ligase required to protect genome stability in response to replication stress (PubMed:25335891, PubMed:26781088, PubMed:27462463, PubMed:26711499, PubMed:26595769, 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).

Biological Process

Biological Process apoptotic process Source:GO_Central1 Publication
Biological Process cellular response to DNA damage stimulus Source:UniProtKB2 Publications
Biological Process negative regulation of interferon-beta production Source:Ensembl
Biological Process negative regulation of NF-kappaB transcription factor activity Source:Ensembl
Biological Process negative regulation of tumor necrosis factor-mediated signaling pathway Source:CACAO1 Publication
Biological Process protein ubiquitination Source:UniProtKB2 Publications
Biological Process protein-DNA covalent cross-linking repair Source:UniProtKB
Biological Process replication fork processing Source:UniProtKB1 Publication
Biological Process signal transduction Source:ProtInc1 Publication

Cellular Location

Nucleus, nucleoplasm
Nucleus, nucleolus
Chromosome
Cytoplasm
Cytoplasm, perinuclear region
In the nucleus, found in close proximity to PCNA, suggesting localization at replication foci (PubMed:26595769).
Localizes to DNA damage sites in response to replication stress (PubMed:26781088, PubMed:26595769, PubMed:26711499).

Involvement in disease

Seckel syndrome 9 (SCKL9):
A form of Seckel syndrome, a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.

PTM

Sumoylated; sumoylation is required for nuclear localization (PubMed:26820530).
Sumoylation increases protein stability, possibly by preventing ubiquitination (PubMed:26820530).
Autoubiquitinated.