Protein: E3 ubiquitin-protein ligase TRAIP (EC 2.3.2.27) (RING finger protein 206) (TRAF-interacting protein) (Q9BWF2)
Organism: Homo sapiens (Human)
Function: E3 ubiquitin ligase required to protect genome stability in response to replication stress. 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. The function in translesion synthesis is however controversial. Acts as a regulator of the spindle assembly checkpoint. Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF. 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.
Subcellular location: Nucleus, nucleoplasm {ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:26595769, ECO:0000269|PubMed:26820530, ECO:0000269|PubMed:30165463}. Nucleus, nucleolus {ECO:0000269|PubMed:14676304, ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:25335891, ECO:0000269|PubMed:27462463, ECO:0000269|PubMed:30165463}. Chromosome {ECO:0000269|PubMed:25335891, ECO:0000269|PubMed:26595769, ECO:0000269|PubMed:26711499, ECO:0000269|PubMed:26781088, ECO:0000269|PubMed:30165463}. Cytoplasm. Cytoplasm, perinuclear region {ECO:0000269|PubMed:14676304}. Note=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:26595769, PubMed:26711499, PubMed:26781088). {ECO:0000269|PubMed:26595769, ECO:0000269|PubMed:26711499, ECO:0000269|PubMed:26781088}.
Interaction partners:
- TNF receptor-associated factor 1
- Ubiquitin carboxyl-terminal hydrolase CYLD
- TNF receptor-associated factor 2
- BRCA1-A complex subunit RAP80
- Fanconi anemia group D2 protein
- Microtubule-associated protein RP/EB family member 2
- Endonuclease 8-like 3
- Cell division control protein 45 homolog
- DNA replication licensing factor MCM7
- Leucine-rich repeat protein 1
Sequence:
MPIRALCTICSDFFDHSRDVAAIHCGHTFHLQCLIQWFETAPSRTCPQCRIQVGKRTIINKLFFDLAQEEENVLDAEFLKNELDNVRAQLSQKDKEKRDSQVIIDTLRDTLEERNATVVSLQQALGKAEMLCSTLKKQMKYLEQQQDETKQAQEEARRLRSKMKTMEQIELLLQSQRPEVEEMIRDMGVGQSAVEQLAVYCVSLKKEYENLKEARKASGEVADKLRKDLFSSRSKLQTVYSELDQAKLELKSAQKDLQSADKEIMSLKKKLTMLQETLNLPPVASETVDRLVLESPAPVEVNLKLRRPSFRDDIDLNATFDVDTPPARPSSSQHGYYEKLCLEKSHSPIQDVPKKICKGPRKESQLSLGGQSCAGEPDEELVGAFPIFVRNAILGQKQPKRPRSESSCSKDVVRTGFDGLGGRTKFIQPTDTVMIRPLPVKPKTKVKQRVRVKTVPSLFQAKLDTFLWS