| Tbio | Regulator of nonsense transcripts 2 |
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.
This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. [provided by RefSeq, Jul 2008]
This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. [provided by RefSeq, Jul 2008]
Comments
Property Summary
| NCBI Gene PubMed Count | 54 |
| Grant Count | 24 |
| R01 Count | 12 |
| Funding | $3,144,203.1 |
| PubMed Score | 51.76 |
| PubTator Score | 34.01 |
| Disease | Z-score | Confidence |
|---|---|---|
| Carcinoma 2,147 | 1.0 | |
| Malignant neoplasm of prostate 67 | ||
| Prostate cancer 172 | 1.0 |
| PMID | Text |
|---|---|
| 26740584 | we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2-eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3 |
| 25002321 | UPF2 binds the FRB domain of SMG1, a region that regulates the related mTOR kinase. |
| 24271394 | UPF2 MIF4G-1 and MIF4G-2 domains appear to have a crucial scaffolding role, while the MIF4G-3 domain is the key module required for triggering nonsense-mediated decay. |
| 24173962 | This study demonstrated the quantitative regulation of Upf1 and Upf2 proteins by ubiquitin-proteasome system and SMG1. |
| 21419344 | Data show that upon binding to Upf2, the regulatory CH domain of Upf1 undergoes a large conformational change, causing the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity. |
| 19556969 | The authors propose that the bipartite mode of UPF2 binding to UPF1 brings the ribosome and the exon junction complex in close proximity by forming a tight complex after an initial weak encounter with either element. |
| 18987618 | Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) |
| 18066079 | UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. |
| 17803942 | The Upf complex communicates with the exon-junction complex and triggers nonsense-mediated decay in the cytoplasm. |
| 16449641 | UPF2-silenced HeLa cells were impaired in their ability to recognize ectopically expressed aberrant premature termination codon transcripts |
| More... |
MPAERKKPASMEEKDSLPNNKEKDCSERRTVSSKERPKDDIKLTAKKEVSKAPEDKKKRLEDDKRKKEDK 1 - 70 ERKKKDEEKVKAEEESKKKEEEEKKKHQEEERKKQEEQAKRQQEEEAAAQMKEKEESIQLHQEAWERHHL 71 - 140 RKELRSKNQNAPDSRPEENFFSRLDSSLKKNTAFVKKLKTITEQQRDSLSHDFNGLNLSKYIAEAVASIV 141 - 210 EAKLKISDVNCAVHLCSLFHQRYADFAPSLLQVWKKHFEARKEEKTPNITKLRTDLRFIAELTIVGIFTD 211 - 280 KEGLSLIYEQLKNIINADRESHTHVSVVISFCRHCGDDIAGLVPRKVKSAAEKFNLSFPPSEIISPEKQQ 281 - 350 PFQNLLKEYFTSLTKHLKRDHRELQNTERQNRRILHSKGELSEDRHKQYEEFAMSYQKLLANSQSLADLL 351 - 420 DENMPDLPQDKPTPEEHGPGIDIFTPGKPGEYDLEGGIWEDEDARNFYENLIDLKAFVPAILFKDNEKSC 421 - 490 QNKESNKDDTKEAKESKENKEVSSPDDLELELENLEINDDTLELEGGDEAEDLTKKLLDEQEQEDEEAST 491 - 560 GSHLKLIVDAFLQQLPNCVNRDLIDKAAMDFCMNMNTKANRKKLVRALFIVPRQRLDLLPFYARLVATLH 561 - 630 PCMSDVAEDLCSMLRGDFRFHVRKKDQINIETKNKTVRFIGELTKFKMFTKNDTLHCLKMLLSDFSHHHI 631 - 700 EMACTLLETCGRFLFRSPESHLRTSVLLEQMMRKKQAMHLDARYVTMVENAYYYCNPPPAEKTVKKKRPP 701 - 770 LQEYVRKLLYKDLSKVTTEKVLRQMRKLPWQDQEVKDYVICCMINIWNVKYNSIHCVANLLAGLVLYQED 771 - 840 VGIHVVDGVLEDIRLGMEVNQPKFNQRRISSAKFLGELYNYRMVESAVIFRTLYSFTSFGVNPDGSPSSL 841 - 910 DPPEHLFRIRLVCTILDTCGQYFDRGSSKRKLDCFLVYFQRYVWWKKSLEVWTKDHPFPIDIDYMISDTL 911 - 980 ELLRPKIKLCNSLEESIRQVQDLEREFLIKLGLVNDKDSKDSMTEGENLEEDEEEEEGGAETEEQSGNES 981 - 1050 EVNEPEEEEGSDNDDDEGEEEEEENTDYLTDSNKENETDEENTEVMIKGGGLKHVPCVEDEDFIQALDKM 1051 - 1120 MLENLQQRSGESVKVHQLDVAIPLHLKSQLRKGPPLGGGEGEAESADTMPFVMLTRKGNKQQFKILNVPM 1121 - 1190 SSQLAANHWNQQQAEQEERMRMKKLTLDINERQEQEDYQEMLQSLAQRPAPANTNRERRPRYQHPKGAPN 1191 - 1260 ADLIFKTGGRRR 1261 - 1272 //
| PMID | Year | Title |
|---|---|---|
| 26740584 | 2016 | Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. |
| 26496610 | 2015 | A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. |
| 25002321 | 2014 | Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD. |
| 24271394 | 2014 | Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2. |
| 24173962 | 2014 | Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells. |
| 23186163 | 2013 | Toward a comprehensive characterization of a human cancer cell phosphoproteome. |
| 22219177 | 2012 | A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants. |
| 21829167 | 2011 | Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. |
| 21419344 | 2011 | Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. |
| More... |
