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UPF2 UPF2 regulator of nonsense mediated mRNA decay [ Homo sapiens (human) ]

Gene ID: 26019, updated on 5-Mar-2024

Summary

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Official Symbol
UPF2provided by HGNC
Official Full Name
UPF2 regulator of nonsense mediated mRNA decayprovided by HGNC
Primary source
HGNC:HGNC:17854
See related
Ensembl:ENSG00000151461 MIM:605529; AllianceGenome:HGNC:17854
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HUPF2; RENT2; smg-3
Summary
This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 11.8), lymph node (RPKM 8.5) and 25 other tissues See more
Orthologs
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Genomic context

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See UPF2 in Genome Data Viewer
Location:
10p14
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (11920022..12043170, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (11931338..12054461, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (11962021..12085169, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376415 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:11835512-11836711 Neighboring gene proline and serine rich 2 Neighboring gene PROSER2 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 652 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:11917739-11918586 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:11923543-11924742 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3027 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:11940130-11941329 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3028 Neighboring gene RNA, U6 small nuclear 1095, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2133 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3029 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3030 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2134 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2135 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3031 Neighboring gene uncharacterized LOC105376416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2136 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2137 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3032 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3033 Neighboring gene dehydrogenase E1 and transketolase domain containing 1 Neighboring gene RNA, U6 small nuclear 88, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP. Gowravaram M, et al. Nat Commun, 2019 Nov 7. PMID 31699982, Free PMC Article
  2. Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2. Clerici M, et al. Nucleic Acids Res, 2014 Feb. PMID 24271394, Free PMC Article
  3. hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay. Wittmann J, et al. Mol Cell Biol, 2006 Feb. PMID 16449641, Free PMC Article
  4. Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2. Xue G, et al. RNA, 2023 Feb. PMID 36456182, Free PMC Article
  5. Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. López-Perrote A, et al. Nucleic Acids Res, 2016 Feb 29. PMID 26740584, Free PMC Article

See all (105) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.
    Title: An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.
  2. Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2.
    Title: Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2.
  3. Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation.
    Title: Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation.
  4. our findings indicate that impaired UPF2-dependent nonsense-mediated decay leads to neurodevelopmental dysfunction
    Title: Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response.
  5. UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an Staufen-mediated mRNA decay-competent mRNP.
    Title: Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP.
  6. we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2-eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3
    Title: Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex.
  7. UPF2 binds the FRB domain of SMG1, a region that regulates the related mTOR kinase.
    Title: Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD.
  8. This study demonstrated the quantitative regulation of Upf1 and Upf2 proteins by ubiquitin-proteasome system and SMG1.
    Title: Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells.
  9. UPF2 MIF4G-1 and MIF4G-2 domains appear to have a crucial scaffolding role, while the MIF4G-3 domain is the key module required for triggering nonsense-mediated decay.
    Title: Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2.
  10. Data show that upon binding to Upf2, the regulatory CH domain of Upf1 undergoes a large conformational change, causing the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity.
    Title: Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2.
Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2019-02-13)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2019-02-13)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA1408, MGC138834, MGC138835, DKFZp434D222

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables telomeric DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in animal organ regeneration IEA
Inferred from Electronic Annotation
more info
  
involved_in liver development IEA
Inferred from Electronic Annotation
more info
  
involved_in mRNA export from nucleus TAS
Traceable Author Statement
more info
 PubMed 
involved_in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasmic ribonucleoprotein granule IDA
Inferred from Direct Assay
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of exon-exon junction complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of exon-exon junction complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
regulator of nonsense transcripts 2
Names
FRS2/UPF2/LEMD3 fusion
LEMD3/UPF2 fusion
UPF2 regulator of nonsense transcripts homolog
nonsense mRNA reducing factor 2
smg-3 homolog, nonsense mediated mRNA decay factor
up-frameshift suppressor 2 homolog
yeast Upf2p homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033936.1 RefSeqGene

    Range
    5362..128149
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_015542.4 → NP_056357.1  regulator of nonsense transcripts 2

    See identical proteins and their annotated locations for NP_056357.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains a different 5' UTR than variant 1 and is the shorter transcript.
    Source sequence(s)
    AF301013, BC114964, DA188353
    Consensus CDS
    CCDS7086.1
    UniProtKB/Swiss-Prot
    A6NLJ5, D3DRS0, Q14BM1, Q5W0J4, Q8N8U1, Q9H1J2, Q9HAU5, Q9NWL1, Q9P2D9, Q9Y4M9
    Related
    ENSP00000350221.5, ENST00000357604.10
    Conserved Domains (3) summary
    smart00543
    Location:773 → 986
    MIF4G; Middle domain of eukaryotic initiation factor 4G (eIF4G)
    pfam04050
    Location:1095 → 1218
    Upf2; Up-frameshift suppressor 2
    cl19727
    Location:358 → 421
    DUF1451; Zinc-ribbon containing domain

  2. NM_080599.3 → NP_542166.1  regulator of nonsense transcripts 2

    See identical proteins and their annotated locations for NP_542166.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) contains a different 5' UTR than variant 2 and is the longer transcript.
    Source sequence(s)
    AF301013, BC114964, DB065422
    Consensus CDS
    CCDS7086.1
    UniProtKB/Swiss-Prot
    A6NLJ5, D3DRS0, Q14BM1, Q5W0J4, Q8N8U1, Q9H1J2, Q9HAU5, Q9NWL1, Q9P2D9, Q9Y4M9
    Related
    ENSP00000380244.2, ENST00000397053.6
    Conserved Domains (3) summary
    smart00543
    Location:773 → 986
    MIF4G; Middle domain of eukaryotic initiation factor 4G (eIF4G)
    pfam04050
    Location:1095 → 1218
    Upf2; Up-frameshift suppressor 2
    cl19727
    Location:358 → 421
    DUF1451; Zinc-ribbon containing domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    11920022..12043170 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047424986.1 → XP_047280942.1  regulator of nonsense transcripts 2 isoform X3

  2. XM_047424987.1 → XP_047280943.1  regulator of nonsense transcripts 2 isoform X2

  3. XM_011519449.4 → XP_011517751.1  regulator of nonsense transcripts 2 isoform X1

    Conserved Domains (2) summary
    smart00543
    Location:168 → 363
    MIF4G; Middle domain of eukaryotic initiation factor 4G (eIF4G)
    cl19727
    Location:358 → 421
    DUF1451; Zinc-ribbon containing domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    11931338..12054461 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054365447.1 → XP_054221422.1  regulator of nonsense transcripts 2 isoform X2

  2. XM_054365446.1 → XP_054221421.1  regulator of nonsense transcripts 2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9HAU5.1 GenPept UniProtKB/Swiss-Prot:Q9HAU5

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