UPF1

UPF1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2GJK, 2GK6, 2GK7, 2IYK, 2WJV, 2WJY, 2XZO, 2XZP
Identifiers
Aliases	UPF1, HNORF1, RENT1, pNORF1, smg-2, RNA helicase and ATPase, UPF1 RNA helicase and ATPase
External IDs	OMIM: 601430 MGI: 107995 HomoloGene: 2185 GeneCards: UPF1
Gene location (Human)
Chr.	Chromosome 19 (human)[1]
End	18,868,236 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	70,353,278 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• nucleotide binding; • DNA binding; • telomeric DNA binding; • zinc ion binding; • chromatin binding; • metal ion binding; • GO:0001948 protein binding; • hydrolase activity; • ATP binding; • GO:0008026 helicase activity; • RNA binding;
Cellular component	• cytosol; • P-body; • exon-exon junction complex; • supraspliceosomal complex; • nucleoplasm; • chromatin; • nuclear chromosome, telomeric region; • cytoplasm; • cell nucleus;
Biological process	• regulation of translational termination; • telomere maintenance via semi-conservative replication; • positive regulation of mRNA catabolic process; • mRNA export from nucleus; • DNA replication; • nuclear-transcribed mRNA catabolic process; • cellular response to interleukin-1; • nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay; • histone mRNA catabolic process; • dosage compensation by inactivation of X chromosome; • cellular response to lipopolysaccharide; • 3'-UTR-mediated mRNA destabilization; • DNA repair; • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; • regulation of telomere maintenance; • cell cycle phase transition; • GO:0022415 viral process;
	Sources:Amigo / QuickGO
Orthologs
	5976
	19704
	ENSG00000005007
	ENSMUSG00000058301
	Q92900
	Q9EPU0
	NM_002911; NM_001297549
	NM_001122829; NM_030680
	NP_001284478; NP_002902; NP_001284478.1
	NP_001116301; NP_109605
	Wikidata
View/Edit Human	View/Edit Mouse

Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.[5][6]

Function

This gene encodes a protein that is part of a post-splicing multiprotein complex, the exon junction 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 both the cytoplasm and nucleus of the cell.[7] When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene.[8]

Interactions

UPF1 has been shown to interact with:

DCP1A,[9]
DCP2,[9][10]
SMG1,[11]
UPF2,[10][11][12][13][14]
UPF3A,[11][12][14] and
UPF3B.[10][12][14]

References

GRCh38: Ensembl release 89: ENSG00000005007 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000058301 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Perlick HA, Medghalchi SM, Spencer FA, Kendzior RJ Jr, Dietz HC (November 1996). "Mammalian orthologues of a yeast regulator of nonsense transcript stability". Proc Natl Acad Sci U S A. 93 (20): 10928–32. doi:10.1073/pnas.93.20.10928. PMC 38260. PMID 8855285.
Applequist SE, Selg M, Raman C, Jack HM (March 1997). "Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein". Nucleic Acids Res. 25 (4): 814–21. doi:10.1093/nar/25.4.814. PMC 146496. PMID 9064659.
Singh AK, Choudhury SR, De S, Zhang J, Kissane S, Dwivedi V, et al. (March 2019). Singer RH, Manley JL (eds.). "The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci". eLife. 8: e41444. doi:10.7554/eLife.41444. PMID 30907728.
"Entrez Gene: UPF1 UPF1 regulator of nonsense transcripts homolog (yeast)".
Lykke-Andersen J (2002). "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay". Mol. Cell. Biol. 22 (23): 8114–21. doi:10.1128/MCB.22.23.8114-8121.2002. PMC 134073. PMID 12417715.
Lejeune F, Li X, Maquat LE (2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities". Mol. Cell. 12 (3): 675–87. doi:10.1016/S1097-2765(03)00349-6. PMID 14527413.
Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S (2001). "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay". Genes Dev. 15 (17): 2215–28. doi:10.1101/gad.913001. PMC 312771. PMID 11544179.
Schell T, Köcher T, Wilm M, Seraphin B, Kulozik AE, Hentze MW (2003). "Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells". Biochem. J. 373 (Pt 3): 775–83. doi:10.1042/BJ20021920. PMC 1223536. PMID 12723973.
Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC (2000). "Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes". Mol. Cell. Biol. 20 (23): 8944–57. doi:10.1128/MCB.20.23.8944-8957.2000. PMC 86549. PMID 11073994.
Lykke-Andersen J, Shu MD, Steitz JA (2000). "Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon". Cell. 103 (7): 1121–31. doi:10.1016/S0092-8674(00)00214-2. PMID 11163187. S2CID 18417600.

Azzalin CM, Lingner J (2006). "The double life of UPF1 in RNA and DNA stability pathways". Cell Cycle. 5 (14): 1496–8. doi:10.4161/cc.5.14.3093. PMID 16861888.
Horikoshi M, Sekimizu K, Natori S (1984). "Analysis of the stimulatory factor of RNA polymerase II in the initiation and elongation complex". J. Biol. Chem. 259 (1): 608–11. PMID 6200476.
Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
Czaplinski K, Ruiz-Echevarria MJ, Paushkin SV, et al. (1998). "The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs". Genes Dev. 12 (11): 1665–77. doi:10.1101/gad.12.11.1665. PMC 316864. PMID 9620853.
Page MF, Carr B, Anders KR, et al. (1999). "SMG-2 Is a Phosphorylated Protein Required for mRNA Surveillance in Caenorhabditis elegans and Related to Upf1p of Yeast". Mol. Cell. Biol. 19 (9): 5943–51. doi:10.1128/MCB.19.9.5943. PMC 84455. PMID 10454541.
Bhattacharya A, Czaplinski K, Trifillis P, et al. (2000). "Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay". RNA. 6 (9): 1226–35. doi:10.1017/S1355838200000546. PMC 1369996. PMID 10999600.
Mendell JT, Medghalchi SM, Lake RG, et al. (2000). "Novel Upf2p Orthologues Suggest a Functional Link between Translation Initiation and Nonsense Surveillance Complexes". Mol. Cell. Biol. 20 (23): 8944–57. doi:10.1128/MCB.20.23.8944-8957.2000. PMC 86549. PMID 11073994.
Serin G, Gersappe A, Black JD, et al. (2001). "Identification and Characterization of Human Orthologues to Saccharomyces cerevisiae Upf2 Protein and Upf3 Protein (Caenorhabditis elegans SMG-4)". Mol. Cell. Biol. 21 (1): 209–23. doi:10.1128/MCB.21.1.209-223.2001. PMC 88795. PMID 11113196.
Lykke-Andersen J, Shu MD, Steitz JA (2001). "Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon". Cell. 103 (7): 1121–31. doi:10.1016/S0092-8674(00)00214-2. PMID 11163187. S2CID 18417600.
Denning G, Jamieson L, Maquat LE, et al. (2001). "Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein". J. Biol. Chem. 276 (25): 22709–14. doi:10.1074/jbc.C100144200. PMID 11331269.
Yamashita A, Ohnishi T, Kashima I, et al. (2001). "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay". Genes Dev. 15 (17): 2215–28. doi:10.1101/gad.913001. PMC 312771. PMID 11544179.
Lykke-Andersen J, Shu MD, Steitz JA (2001). "Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1". Science. 293 (5536): 1836–9. doi:10.1126/science.1062786. PMID 11546874. S2CID 389385.
Carastro LM, Tan CK, Selg M, et al. (2002). "Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta". Nucleic Acids Res. 30 (10): 2232–43. doi:10.1093/nar/30.10.2232. PMC 115286. PMID 12000843.
Mendell JT, ap Rhys CM, Dietz HC (2002). "Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts". Science. 298 (5592): 419–22. doi:10.1126/science.1074428. PMID 12228722. S2CID 46447414.
Lykke-Andersen J (2003). "Identification of a Human Decapping Complex Associated with hUpf Proteins in Nonsense-Mediated Decay". Mol. Cell. Biol. 22 (23): 8114–21. doi:10.1128/MCB.22.23.8114-8121.2002. PMC 134073. PMID 12417715.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Chiu SY, Serin G, Ohara O, Maquat LE (2003). "Characterization of human Smg5/7a: A protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1". RNA. 9 (1): 77–87. doi:10.1261/rna.2137903. PMC 1370372. PMID 12554878.
Schell T, Köcher T, Wilm M, et al. (2003). "Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells". Biochem. J. 373 (Pt 3): 775–83. doi:10.1042/BJ20021920. PMC 1223536. PMID 12723973.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000005007 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000058301 - 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.

[pmid8855285-5] Perlick HA, Medghalchi SM, Spencer FA, Kendzior RJ Jr, Dietz HC (November 1996). "Mammalian orthologues of a yeast regulator of nonsense transcript stability". Proc Natl Acad Sci U S A. 93 (20): 10928–32. doi:10.1073/pnas.93.20.10928. PMC 38260. PMID 8855285.

[pmid9064659-6] Applequist SE, Selg M, Raman C, Jack HM (March 1997). "Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein". Nucleic Acids Res. 25 (4): 814–21. doi:10.1093/nar/25.4.814. PMC 146496. PMID 9064659.

[7] Singh AK, Choudhury SR, De S, Zhang J, Kissane S, Dwivedi V, et al. (March 2019). Singer RH, Manley JL (eds.). "The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci". eLife. 8: e41444. doi:10.7554/eLife.41444. PMID 30907728.

[entrez-8] "Entrez Gene: UPF1 UPF1 regulator of nonsense transcripts homolog (yeast)".

[pmid12417715-9] Lykke-Andersen J (2002). "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay". Mol. Cell. Biol. 22 (23): 8114–21. doi:10.1128/MCB.22.23.8114-8121.2002. PMC 134073. PMID 12417715.

[pmid14527413-10] Lejeune F, Li X, Maquat LE (2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities". Mol. Cell. 12 (3): 675–87. doi:10.1016/S1097-2765(03)00349-6. PMID 14527413.

[pmid11544179-11] Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S (2001). "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay". Genes Dev. 15 (17): 2215–28. doi:10.1101/gad.913001. PMC 312771. PMID 11544179.

[pmid12723973-12] Schell T, Köcher T, Wilm M, Seraphin B, Kulozik AE, Hentze MW (2003). "Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells". Biochem. J. 373 (Pt 3): 775–83. doi:10.1042/BJ20021920. PMC 1223536. PMID 12723973.

[pmid11073994-13] Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC (2000). "Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes". Mol. Cell. Biol. 20 (23): 8944–57. doi:10.1128/MCB.20.23.8944-8957.2000. PMC 86549. PMID 11073994.

[pmid11163187-14] Lykke-Andersen J, Shu MD, Steitz JA (2000). "Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon". Cell. 103 (7): 1121–31. doi:10.1016/S0092-8674(00)00214-2. PMID 11163187. S2CID 18417600.

UPF1

Function

Interactions

References

Further reading