UPF1

Chr 19p13.11

UPF1 RNA helicase and ATPase

Aliases:: HUPF1, KIAA0221, NORF1, pNORF1, smg-2
MANE:: ENST00000262803.10

OMIM: 601430 ↗NCBI: 5976 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

UPF1 · Q92900

v62025-08-01

Predicted Aligned Error matrix for UPF1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

72.8/ 100

Confident

1,129 residues

Confidence breakdown

Very high(≥ 90)41%
Confident(70–90)25%
Low(50–70)5%
Very low(< 50)29%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

Intellectual disability
0.44
Global developmental delay
0.43
Frontal bossing
0.43
High anterior hairline
0.43
Hypertelorism
0.43
neurodevelopmental disorder
0.42
complex neurodevelopmental disorder
0.37
Strabismus
0.34
Thin upper lip vermilion
0.34
gastritis
0.28

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Regulator of nonsense transcripts 1

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)