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Regulator of nonsense transcripts 1

 
Known also as: ATP-dependent helicase RENT1, Nonsense mRNA reducing factor 1,Up-frameshift suppressor 1 homolog

Known abbreviations: UPF1,hUpf1,NORF1, KIAA0221, RENT1

 

FUNCTION:
 
RNA-dependent helicase and ATPase required for nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability. 
 
SUBUNIT STRUCTURE:
 
Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Associates with the SGM1C complex; is phosphorylated by the complex kinase component SGM1. Interacts with UPF2, UPF3A and UPF3B. Interacts with EST1A and SLBP. Interacts (when hyperphosphorylated) with PNRC2. Interacts with EIF2C1, EIF2C2 and GSPT2. 
 
CELLULAR LOCALIZATION:
 
Cytoplasm. Cytoplasm › P-body. Note: Hyperphosphorylated form is targeted to the P-body, while unphosphorylated protein is distributed throughout the cytoplasm.
 
TISSUE SPECIFICITY:
 
Ubiquitous.
 
DOMAIN:
 
The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
 
POST-TRANSLATIONAL MODIFICATION:
 
Phosphorylated by SMG1; required for formation of mRNA surveillance complexes. Phosphorylated upon DNA damage, probably by ATM or ATR.
 



This protein can be a part of a given complexes: Activities in which Regulator of nonsense transcripts 1 is involved: Pathways in which Regulator of nonsense transcripts 1 is involved:

NCBI GI number(s): 18375673
88853067
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q92900 Q92900
BRENDA - -
KEGG hsa:5976 hsa:5976
PFAM: PF09416
PF09416
InterPro: IPR018999
IPR018999
CATH: - -
SCOP: - -
Solved crystal structures: 2XZP
2XZO
2WJY
2WJV
2IYK
2GK7
2GK6
2GJK
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]


Protein sequence:
MSVEAYGPSSQTLTFLDTEEAELLGADTQGSEFEFTDFTLPSQTQTPPGG
PGGPGGGGAGGPGGAGAGAAAGQLDAQVGPEGILQNGAVDDSVAKTSQLL
AELNFEEDEEDTYYTKDLPIHACSYCGIHDPACVVYCNTSKKWFCNGRGN
TSGSHIVNHLVRAKCKEVTLHKDGPLGETVLECYNCGCRNVFLLGFIPAK
ADSVVVLLCRQPCASQSSLKDINWDSSQWQPLIQDRCFLSWLVKIPSEQE
QLRARQITAQQINKLEELWKENPSATLEDLEKPGVDEEPQHVLLRYEDAY
QYQNIFGPLVKLEADYDKKLKESQTQDNITVRWDLGLNKKRIAYFTLPKT
DSGNEDLVIIWLRDMRLMQGDEICLRYKGDLAPLWKGIGHVIKVPDNYGD
EIAIELRSSVGAPVEVTHNFQVDFVWKSTSFDRMQSALKTFAVDETSVSG
YIYHKLLGHEVEDVIIKCQLPKRFTAQGLPDLNHSQVYAVKTVLQRPLSL
IQGPPGTGKTVTSATIVYHLARQGNGPVLVCAPSNIAVDQLTEKIHQTGL
KVVRLCAKSREAIDSPVSFLALHNQIRNMDSMPELQKLQQLKDETGELSS
ADEKRYRALKRTAERELLMNADVICCTCVGAGDPRLAKMQFRSILIDEST
QATEPECMVPVVLGAKQLILVGDHCQLGPVVMCKKAAKAGLSQSLFERLV
VLGIRPIRLQVQYRMHPALSAFPSNIFYEGSLQNGVTAADRVKKGFDFQW
PQPDKPMFFYVTQGQEEIASSGTSYLNRTEAANVEKITTKLLKAGAKPDQ
IGIITPYEGQRSYLVQYMQFSGSLHTKLYQEVEIASVDAFQGREKDFIIL
SCVRANEHQGIGFLNDPRRLNVALTRARYGVIIVGNPKALSKQPLWNHLL
NYYKEQKVLVEGPLNNLRESLMQFSKPRKLVNTINPGARFMTTAMYDARE
AIIPGSVYDRSSQGRPSSMYFQTHDQIGMISAGPSHVAAMNIPIPFNLVM
PPMPPPGYFGQANGPAAGRGTPKGKTGRGGRQKNRFGLPGPSQTNLPNSQ
ASQDVASQPFSQGALTQGYISMSQPSQMSQPGLSQPELSQDSYLGDEFKS
QIDVALSQDSTYQGERAYQHGGVTGLSQY

Regulator of nonsense transcripts 1 (Homo sapiens) is product of expression of UPF1 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A, Hachiya T, Hentze MW, Anderson P, Ohno S Mol Cell 2003-11-01 (12) 14636577
SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway. Fukuhara N, Ebert J, Unterholzner L, Lindner D, Izaurralde E, Conti E Mol Cell 2005-01-18 (17) 15721257
SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Yamashita A, Izumi N, Kashima I, Ohnishi T, Saari B, Katsuhata Y, Muramatsu R, Morita T, Iwamatsu A, Hachiya T, Kurata R, Hirano H, Anderson P, Ohno S Genes Dev 2009-05-01 (23) 19417104
Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. Chiu SY, Serin G, Ohara O, Maquat LE RNA 2003-02-01 (9) 12554878
Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. Bhattacharya A, Czaplinski K, Trifillis P, He F, Jacobson A, Peltz SW RNA 2000-09-01 (6) 10999600
Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein. Applequist SE, Selg M, Raman C, Jack HM Nucleic Acids Res 1997-01-15 (25) 9064659
Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Lykke-Andersen J, Shu MD, Steitz JA Cell 2000-12-22 (103) 11163187
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 Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S Genes Dev 2001-09-01 (15) 11544179
Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. Denning G, Jamieson L, Maquat LE, Thompson EA, Fields AP J Biol Chem 2001-06-22 (276) 11331269
Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Lykke-Andersen J, Shu MD, Steitz JA Science 2001-09-07 (293) 11546874
Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Mullen TE, Marzluff WF Genes Dev 2008-02-01 (22) 18172165
Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Cho H, Kim KM, Kim YK Mol Cell 2009-02-16 (33) 19150429
The DNA sequence and biology of human chromosome 19. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M Nature 2004-04-01 (428) 15057824
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem 2009-06-01 (81) 19413330
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science 2007-05-25 (316) 17525332
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A 2008-08-05 (105) 18669648
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal 2009-01-01 (2) 19690332
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. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N DNA Res 1996-10-31 (3) 9039502
Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd J Proteome Res 2008-03-01 (7) 18220336
Mammalian orthologues of a yeast regulator of nonsense transcript stability. Perlick HA, Medghalchi SM, Spencer FA, Kendzior RJ Jr, Dietz HC Proc Natl Acad Sci U S A 1996-10-01 (93) 8855285
SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. Page MF, Carr B, Anders KR, Grimson A, Anderson P Mol Cell Biol 1999-09-01 (19) 10454541
Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes. Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC Mol Cell Biol 2000-12-01 (20) 11073994
Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE Mol Cell Biol 2001-02-01 (21) 11113196
Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1. Kaygun H, Marzluff WF Nat Struct Mol Biol 2005-09-01 (12) 16086026
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Kashima I, Yamashita A, Izumi N, Kataoka N, Morishita R, Hoshino S, Ohno M, Dreyfuss G, Ohno S Genes Dev 2006-01-01 (20) 16452507
Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. Hock J, Weinmann L, Ender C, Rudel S, Kremmer E, Raabe M, Urlaub H, Meister G EMBO Rep 2007-11-01 (8) 17932509
A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay. Singh G, Rebbapragada I, Lykke-Andersen J PLoS Biol 2008-04-01 (6) 18447585
Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Franks TM, Singh G, Lykke-Andersen J Cell 2010-12-10 (143) 21145460
Structural and functional insights into the human Upf1 helicase core. Cheng Z, Muhlrad D, Lim MK, Parker R, Song H EMBO J 2007-02-10 (26) 17159905
Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2. Clerici M, Mourao A, Gutsche I, Gehring NH, Hentze MW, Kulozik A, Kadlec J, Sattler M, Cusack S EMBO J 2009-08-05 (28) 19556969



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Last modification of this entry: Sept. 25, 2012.

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