CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-018868
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Regulator of nonsense transcripts 1 
Protein Synonyms/Alias
 ATP-dependent helicase RENT1; Nonsense mRNA reducing factor 1; NORF1; Up-frameshift suppressor 1 homolog; hUpf1 
Gene Name
 UPF1 
Gene Synonyms/Alias
 KIAA0221; RENT1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
220CASQSSLKDINWDSSubiquitination[1]
264ITAQQINKLEELWKEubiquitination[2, 3, 4]
282ATLEDLEKPGVDEEPubiquitination[5, 6]
321ADYDKKLKESQTQDNubiquitination[3, 5]
339RWDLGLNKKRIAYFTubiquitination[2, 4]
340WDLGLNKKRIAYFTLubiquitination[3]
378DEICLRYKGDLAPLWubiquitination[2, 3, 4]
386GDLAPLWKGIGHVIKubiquitination[2, 3, 4, 6, 7]
439DRMQSALKTFAVDETubiquitination[1, 2, 3, 4, 6, 7, 8, 9, 10, 11]
455VSGYIYHKLLGHEVEubiquitination[1, 3]
467EVEDVIIKCQLPKRFubiquitination[3]
544AVDQLTEKIHQTGLKubiquitination[3]
551KIHQTGLKVVRLCAKubiquitination[6]
587DSMPELQKLQQLKDEubiquitination[2, 4, 5, 7, 11]
592LQKLQQLKDETGELSacetylation[6, 12]
604ELSSADEKRYRALKRubiquitination[3, 5, 6, 11]
638AGDPRLAKMQFRSILubiquitination[2, 3, 4, 6, 9]
688VMCKKAAKAGLSQSLubiquitination[2, 3, 4]
786TEAANVEKITTKLLKacetylation[6]
786TEAANVEKITTKLLKubiquitination[3, 6]
790NVEKITTKLLKAGAKubiquitination[2, 3, 4, 6]
793KITTKLLKAGAKPDQubiquitination[3, 7, 11]
797KLLKAGAKPDQIGIIubiquitination[3, 5]
845DAFQGREKDFIILSCubiquitination[3]
888VIIVGNPKALSKQPLubiquitination[3]
892GNPKALSKQPLWNHLubiquitination[3]
926ESLMQFSKPRKLVNTubiquitination[2, 3, 4, 6]
929MQFSKPRKLVNTINPubiquitination[3, 6, 10]
Reference
 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [9] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [11] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [12] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 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. 
Sequence Annotation
 ZN_FING 121 272 UPF1-type.
 NP_BIND 506 510 ATP.
 REGION 1 415 Sufficient for interaction with RENT2.
 MOTIF 1089 1090 [ST]-Q motif 1.
 MOTIF 1107 1108 [ST]-Q motif 2.
 BINDING 486 486 ATP.
 BINDING 676 676 ATP.
 BINDING 713 713 ATP.
 BINDING 844 844 ATP.
 MOD_RES 1089 1089 Phosphoserine.
 MOD_RES 1107 1107 Phosphoserine.
 MOD_RES 1110 1110 Phosphoserine.
 MOD_RES 1127 1127 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Helicase; Hydrolase; Metal-binding; Nonsense-mediated mRNA decay; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1129 AA 
Protein Sequence
MSVEAYGPSS QTLTFLDTEE AELLGADTQG SEFEFTDFTL PSQTQTPPGG PGGPGGGGAG 60
GPGGAGAGAA AGQLDAQVGP EGILQNGAVD DSVAKTSQLL AELNFEEDEE DTYYTKDLPI 120
HACSYCGIHD PACVVYCNTS KKWFCNGRGN TSGSHIVNHL VRAKCKEVTL HKDGPLGETV 180
LECYNCGCRN VFLLGFIPAK ADSVVVLLCR QPCASQSSLK DINWDSSQWQ PLIQDRCFLS 240
WLVKIPSEQE QLRARQITAQ QINKLEELWK ENPSATLEDL EKPGVDEEPQ HVLLRYEDAY 300
QYQNIFGPLV KLEADYDKKL KESQTQDNIT VRWDLGLNKK RIAYFTLPKT DSGNEDLVII 360
WLRDMRLMQG DEICLRYKGD LAPLWKGIGH VIKVPDNYGD EIAIELRSSV GAPVEVTHNF 420
QVDFVWKSTS FDRMQSALKT FAVDETSVSG YIYHKLLGHE VEDVIIKCQL PKRFTAQGLP 480
DLNHSQVYAV KTVLQRPLSL IQGPPGTGKT VTSATIVYHL ARQGNGPVLV CAPSNIAVDQ 540
LTEKIHQTGL KVVRLCAKSR EAIDSPVSFL ALHNQIRNMD SMPELQKLQQ LKDETGELSS 600
ADEKRYRALK RTAERELLMN ADVICCTCVG AGDPRLAKMQ FRSILIDEST QATEPECMVP 660
VVLGAKQLIL VGDHCQLGPV VMCKKAAKAG LSQSLFERLV VLGIRPIRLQ VQYRMHPALS 720
AFPSNIFYEG SLQNGVTAAD RVKKGFDFQW PQPDKPMFFY VTQGQEEIAS SGTSYLNRTE 780
AANVEKITTK LLKAGAKPDQ IGIITPYEGQ RSYLVQYMQF SGSLHTKLYQ EVEIASVDAF 840
QGREKDFIIL SCVRANEHQG IGFLNDPRRL NVALTRARYG VIIVGNPKAL SKQPLWNHLL 900
NYYKEQKVLV EGPLNNLRES LMQFSKPRKL VNTINPGARF MTTAMYDARE AIIPGSVYDR 960
SSQGRPSSMY FQTHDQIGMI SAGPSHVAAM NIPIPFNLVM PPMPPPGYFG QANGPAAGRG 1020
TPKGKTGRGG RQKNRFGLPG PSQTNLPNSQ ASQDVASQPF SQGALTQGYI SMSQPSQMSQ 1080
PGLSQPELSQ DSYLGDEFKS QIDVALSQDS TYQGERAYQH GGVTGLSQY 1129 
Gene Ontology
 GO:0000785; C:chromatin; IDA:HGNC.
 GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
 GO:0044530; C:supraspliceosomal complex; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004004; F:ATP-dependent RNA helicase activity; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IDA:HGNC.
 GO:0003677; F:DNA binding; IEA:InterPro.
 GO:0003723; F:RNA binding; NAS:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007049; P:cell cycle; IMP:HGNC.
 GO:0006281; P:DNA repair; IDA:HGNC.
 GO:0006260; P:DNA replication; IMP:HGNC.
 GO:0009048; P:dosage compensation by inactivation of X chromosome; IEA:Compara.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0071044; P:histone mRNA catabolic process; IMP:UniProtKB.
 GO:0006406; P:mRNA export from nucleus; TAS:HGNC.
 GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
 GO:0006449; P:regulation of translational termination; IMP:UniProtKB. 
Interpro
 IPR027417; P-loop_NTPase.
 IPR018999; RNA-helicase_UPF1_UPF2-interct. 
Pfam
 PF09416; UPF1_Zn_bind 
SMART
  
PROSITE
  
PRINTS