InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: UPF1

Summary

InnateDB Protein

IDBP-38887.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

UPF1

Protein Name

UPF1 regulator of nonsense transcripts homolog (yeast)

Synonyms

HUPF1; NORF1; pNORF1; RENT1; smg-2;

Species

Homo sapiens

Ensembl Protein

ENSP00000262803

InnateDB Gene

IDBG-38885 (UPF1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11163187, ECO:0000269PubMed:16086026, ECO:0000269PubMed:18172165, ECO:0000269PubMed:21145460, ECO:0000269PubMed:21419344}.

Subcellular Localization

Cytoplasm. Cytoplasm, P-body. Nucleus. Note=Hyperphosphorylated form is targeted to the P-body, while unphosphorylated protein is distributed throughout the cytoplasm.

Disease Associations

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 155 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	155 [view]
Protein-Protein	153 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003723	RNA binding
GO:0004004	ATP-dependent RNA helicase activity
GO:0004386	helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016787	hydrolase activity
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0000956	nuclear-transcribed mRNA catabolic process
GO:0006200	ATP catabolic process
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006406	mRNA export from nucleus
GO:0006449	regulation of translational termination
GO:0010467	gene expression
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0071044	histone mRNA catabolic process

Cellular Component

GO:0000785	chromatin
GO:0000932	cytoplasmic mRNA processing body
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0035145	exon-exon junction complex
GO:0044530	supraspliceosomal complex