Search Results

Overview

Uniprot ID	Q92900
Protein Name	Regulator of nonsense transcripts 1
Gene Name	UPF1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
929	MQFSKPRKLVNTINP

Function

RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and which modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:16086026, PubMed:18172165, PubMed:21145460, PubMed:21419344, PubMed:24726324). ATP-dependent 5'-3' helicase active on RNA:DNA substrates with a 5'-RNA extension (PubMed:18066079, PubMed:21419344, PubMed:23275559, PubMed:26138914). ATP-dependent 5'-3' helicase active on RNA:RNA substrates with a 5'-RNA extension (PubMed:26138914). ATP-dependent 5'-3' helicase active on DNA:DNA substrates with a 5'-DNA extension (PubMed:10999600, PubMed:26138914, PubMed:30218034). 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 (PubMed:11544179, PubMed:25220460). Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). 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 (PubMed:21419344). 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 (PubMed:12554878). UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585). Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165). 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 (PubMed:18447585, PubMed:25220460). The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460). Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity). Has ssDNA-stimulated ATPase activity (poly(dT) and poly(dA) are most stimulatory) (PubMed:10999600). Binds RNA; addition of ATP decreases RNA-binding (PubMed:10999600, PubMed:18066079, PubMed:21419344)

Protein Sequence

10 MSVEAYGPSS 20 QTLTFLDTEE 30 AELLGADTQG 40 SEFEFTDFTL 50 PSQTQTPPGG 60 PGGPGGGGAG 70 GPGGAGAGAA 80 AGQLDAQVGP 90 EGILQNGAVD 100 DSVAKTSQLL 110 AELNFEEDEE 120 DTYYTKDLPI 130 HACSYCGIHD 140 PACVVYCNTS 150 KKWFCNGRGN 160 TSGSHIVNHL 170 VRAKCKEVTL 180 HKDGPLGETV 190 LECYNCGCRN 200 VFLLGFIPAK 210 ADSVVVLLCR 220 QPCASQSSLK 230 DINWDSSQWQ 240 PLIQDRCFLS 250 WLVKIPSEQE 260 QLRARQITAQ 270 QINKLEELWK 280 ENPSATLEDL 290 EKPGVDEEPQ 300 HVLLRYEDAY 310 QYQNIFGPLV 320 KLEADYDKKL 330 KESQTQDNIT 340 VRWDLGLNKK 350 RIAYFTLPKT 360 DSGNEDLVII 370 WLRDMRLMQG 380 DEICLRYKGD 390 LAPLWKGIGH 400 VIKVPDNYGD 410 EIAIELRSSV 420 GAPVEVTHNF 430 QVDFVWKSTS 440 FDRMQSALKT 450 FAVDETSVSG 460 YIYHKLLGHE 470 VEDVIIKCQL 480 PKRFTAQGLP 490 DLNHSQVYAV 500 KTVLQRPLSL 510 IQGPPGTGKT 520 VTSATIVYHL 530 ARQGNGPVLV 540 CAPSNIAVDQ 550 LTEKIHQTGL 560 KVVRLCAKSR 570 EAIDSPVSFL 580 ALHNQIRNMD 590 SMPELQKLQQ 600 LKDETGELSS 610 ADEKRYRALK 620 RTAERELLMN 630 ADVICCTCVG 640 AGDPRLAKMQ 650 FRSILIDEST 660 QATEPECMVP 670 VVLGAKQLIL 680 VGDHCQLGPV 690 VMCKKAAKAG 700 LSQSLFERLV 710 VLGIRPIRLQ 720 VQYRMHPALS 730 AFPSNIFYEG 740 SLQNGVTAAD 750 RVKKGFDFQW 760 PQPDKPMFFY 770 VTQGQEEIAS 780 SGTSYLNRTE 790 AANVEKITTK 800 LLKAGAKPDQ 810 IGIITPYEGQ 820 RSYLVQYMQF 830 SGSLHTKLYQ 840 EVEIASVDAF 850 QGREKDFIIL 860 SCVRANEHQG 870 IGFLNDPRRL 880 NVALTRARYG 890 VIIVGNPKAL 900 SKQPLWNHLL 910 NYYKEQKVLV 920 EGPLNNLRES 930 LMQFSKPRKL 940 VNTINPGARF 950 MTTAMYDARE 960 AIIPGSVYDR 970 SSQGRPSSMY 980 FQTHDQIGMI 990 SAGPSHVAAM 1000 NIPIPFNLVM 1010 PPMPPPGYFG 1020 QANGPAAGRG 1030 TPKGKTGRGG 1040 RQKNRFGLPG 1050 PSQTNLPNSQ 1060 ASQDVASQPF 1070 SQGALTQGYI 1080 SMSQPSQMSQ 1090 PGLSQPELSQ 1100 DSYLGDEFKS 1110 QIDVALSQDS 1120 TYQGERAYQH GGVTGLSQY

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000785	chromatin
Cellular Component	GO:0000781	chromosome, telomeric region
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0035145	exon-exon junction complex
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0000932	P-body
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0044530	supraspliceosomal complex
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0016887	ATP hydrolysis activity
Molecular Function	GO:0003682	chromatin binding
Molecular Function	GO:0036121	double-stranded DNA helicase activity
Molecular Function	GO:0004386	helicase activity
Molecular Function	GO:0044877	protein-containing complex binding
Molecular Function	GO:0003723	RNA binding
Molecular Function	GO:0003724	RNA helicase activity
Molecular Function	GO:0042162	telomeric DNA binding
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0061158	3'-UTR-mediated mRNA destabilization
Biological Process	GO:0044770	cell cycle phase transition
Biological Process	GO:0071347	cellular response to interleukin-1
Biological Process	GO:0071222	cellular response to lipopolysaccharide
Biological Process	GO:0006281	DNA repair
Biological Process	GO:0006260	DNA replication
Biological Process	GO:0071044	histone mRNA catabolic process
Biological Process	GO:0006406	mRNA export from nucleus
Biological Process	GO:0000956	nuclear-transcribed mRNA catabolic process
Biological Process	GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Biological Process	GO:0061014	positive regulation of mRNA catabolic process
Biological Process	GO:0032204	regulation of telomere maintenance
Biological Process	GO:0006449	regulation of translational termination
Biological Process	GO:0032201	telomere maintenance via semi-conservative replication

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.