TRAF interacting protein

TRAIP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZTD
Identifiers
Aliases	TRAIP , RNF206, TRIP, SCKL9, TRAF interacting protein
External IDs	OMIM: 605958; MGI: 1096377; HomoloGene: 31343; GeneCards: TRAIP; OMA:TRAIP - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p21.31 Start 49,828,601 bp [1] End 49,856,574 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9 F1|9 59.07 cM Start 107,827,335 bp [2] End 107,849,469 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle gonad ventricular zone ganglionic eminence mucosa of transverse colon left testis right testis stromal cell of endometrium rectum nucleus accumbens Top expressed in tail of embryo gastrula genital tubercle fetal liver hematopoietic progenitor cell morula morula otic placode zygote yolk sac embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ubiquitin-protein transferase activity protein binding metal ion binding ubiquitin protein ligase activity transferase activity zinc ion binding Cellular component cytoplasm perinuclear region of cytoplasm nucleolus nucleus Biological process cell population proliferation protein ubiquitination negative regulation of interferon-beta production signal transduction negative regulation of tumor necrosis factor-mediated signaling pathway apoptotic process negative regulation of NF-kappaB transcription factor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10293 22036 Ensembl ENSG00000183763 ENSMUSG00000032586 UniProt Q9BWF2 Q8VIG6 RefSeq (mRNA) NM_005879 NM_011634 RefSeq (protein) NP_005870 NP_035764 Location (UCSC) Chr 3: 49.83 – 49.86 Mb Chr 9: 107.83 – 107.85 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The AlphaFold predicted structure of the TRAIP protein Q9BWF2. The highlighted region has been found to bind to the PCNA PIP box. This image was generated using ChimeraX version 1.7.1.

Detailed view of residue sequence 447-469 of the TRAIP protein in its binding conformation with the PCNA PIP box. This This image was generated using ChimeraX version 1.7.1.

TRAF-interacting protein is a protein that in humans is encoded by the TRAIP gene. ^{[6] [7]}

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. ^[7]

Interactions

TRAF interacting protein has been shown to interact with FLII, ^[8] TRAF1 ^[6] and TRAF2. ^[6]

Role in mitotic DNA synthesis

Mitotic DNA synthesis (MiDAS) is thought to be a DNA repair mechanism to salvage DNA that has not finished replication during S phase, which may be due to DNA replication stress (RS). ^[9] Intrinsic sources of RS include transcription-replication conflicts and “difficult-to-replicate’’ regions. ^[9] Extrinsic RS includes exposure to genotoxic agents, depletion of dNTPs, and premature S phase activity which can occur in precancerous cells after oncogene activation. ^[9] Some MiDAS pathways require the TRAIP protein to disassemble the replication complex at the stalled replication fork in cases where RS causes the fork to stall during replication. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000183763 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032586 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hoffmann S, Smedegaard S, Nakamura K, Mortuza GB, Räschle M, Ibañez de Opakua A, et al. (January 2016). "TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress". The Journal of Cell Biology. 212 (1): 63–75. doi:10.1083/jcb.201506071. PMC   4700480 . PMID   26711499.
6. Lee SY, Lee SY, Choi Y (April 1997). "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation". The Journal of Experimental Medicine. 185 (7): 1275–1285. doi:10.1084/jem.185.7.1275. PMC   2196258 . PMID   9104814.
7. "Entrez Gene: TRAIP TRAF interacting protein".
8. Wilson SA, Brown EC, Kingsman AJ, Kingsman SM (August 1998). "TRIP: a novel double stranded RNA binding protein which interacts with the leucine rich repeat of flightless I". Nucleic Acids Research. 26 (15): 3460–3467. doi:10.1093/nar/26.15.3460. PMC   147727 . PMID   9671805.
9. Bhowmick R, Hickson ID, Liu Y (October 2023). "Completing genome replication outside of S phase". Molecular Cell. 83 (20): 3596–3607. doi: 10.1016/j.molcel.2023.08.023 . PMID   37716351.

Further reading

• Beckly JB, Hancock L, Geremia A, Cummings JR, Morris A, Cooney R, et al. (April 2008). "Two-stage candidate gene study of chromosome 3p demonstrates an association between nonsynonymous variants in the MST1R gene and Crohn's disease". Inflammatory Bowel Diseases. 14 (4): 500–507. doi:10.1002/ibd.20365. PMID   18200509. S2CID   37697301.
• Regamey A, Hohl D, Liu JW, Roger T, Kogerman P, Toftgard R, et al. (December 2003). "The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor". The Journal of Experimental Medicine. 198 (12): 1959–1964. doi:10.1084/jem.20031187. PMC   2194148 . PMID   14676304.
• Wilson SA, Brown EC, Kingsman AJ, Kingsman SM (August 1998). "TRIP: a novel double stranded RNA binding protein which interacts with the leucine rich repeat of flightless I". Nucleic Acids Research. 26 (15): 3460–3467. doi:10.1093/nar/26.15.3460. PMC   147727 . PMID   9671805.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.

External links

• TRAIP human gene location in the UCSC Genome Browser .
• TRAIP human gene details in the UCSC Genome Browser .