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

Summary

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: mouse all
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Genomic context

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_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.
Title: An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-37657 (e-PCR)
- UniSTS:18969

PMC86549P1 (e-PCR)
- UniSTS:273530

SHGC-111377 (e-PCR)
- UniSTS:182179

RH18142 (e-PCR)
- UniSTS:209594

STS-N72687 (e-PCR)
- UniSTS:45764

SHGC-149225 (e-PCR)
- UniSTS:176874

WI-20284 (e-PCR)
- UniSTS:27900

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

NG_033936.1 RefSeqGene

Range

5362..128149

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

11920022..12043170 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047424986.1 → XP_047280942.1 regulator of nonsense transcripts 2 isoform X3
XM_047424987.1 → XP_047280943.1 regulator of nonsense transcripts 2 isoform X2
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