UPF3B

Last updated
UPF3B
Protein UPF3B PDB 1uw4.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases UPF3B , HMRX62, MRXS14, RENT3B, UPF3X, Upf3p-X, UPF3BP1, UPF3BP2, UPF3BP3, UPF3 regulator of nonsense transcripts homolog B (yeast), UPF3 regulator of nonsense transcripts homolog B, regulator of nonsense mediated mRNA decay, UPF3B regulator of nonsense mediated mRNA decay, MRX82
External IDs OMIM: 300298 MGI: 1915384 HomoloGene: 11307 GeneCards: UPF3B
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_023010
NM_080632

NM_026573

RefSeq (protein)

NP_075386
NP_542199

n/a

Location (UCSC) Chr X: 119.81 – 119.85 Mb Chr X: 37.09 – 37.11 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Regulator of nonsense transcripts 3B is a protein that in humans is encoded by the UPF3B gene. [5] [6] [7]

Contents

This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. 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 binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome X. Two splice variants encoding different isoforms have been found for this gene. [7]

Interactions

UPF3B has been shown to interact with UPF2 [6] [8] [9] [10] and UPF1. [6] [9] [11]

Related Research Articles

Nonsense-mediated decay Elimination of mRNA with premature stop codons in eukaryotes

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberrant mRNAs could, in some cases, lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins.

Cap binding complex Formation on 5 ends of mRNAs

The 5' cap of eukaryotic messenger RNA is bound at all times by various cap-binding complexes (CBCs).

RBM8A Protein-coding gene in the species Homo sapiens

RNA-binding protein 8A is a protein that in humans is encoded by the RBM8A gene.

UPF1 Protein-coding gene in the species Homo sapiens

Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.

UPF2

Regulator of nonsense transcripts 2 is a protein that in humans is encoded by the UPF2 gene.

DCP2 Protein found in humans

mRNA-decapping enzyme 2 is a protein that in humans is encoded by the DCP2 gene.

SMG1

Serine/threonine-protein kinase SMG1 is an enzyme that in humans is encoded by the SMG1 gene. SMG1 belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

Exosome component 10 Protein-coding gene in the species Homo sapiens

Exosome component 10, also known as EXOSC10, is a human gene, the protein product of which is part of the exosome complex and is an autoantigen is patients with certain auto immune diseases, most notably scleromyositis.

EIF4A3 Protein-coding gene in the species Homo sapiens

Eukaryotic initiation factor 4A-III is a protein that in humans is encoded by the EIF4A3 gene.

Exosome component 4 Protein-coding gene in the species Homo sapiens

Exosome component 4, also known as EXOSC4, is a human gene, which is part of the exosome complex.

CASC3

Protein CASC3 is a protein that in humans is encoded by the CASC3 gene.

UPF3A Protein-coding gene in the species Homo sapiens

Regulator of nonsense transcripts 3A is a protein that in humans is encoded by the UPF3A gene.

SMG6

Telomerase-binding protein EST1A is an enzyme that in humans is encoded by the SMG6 gene on chromosome 17. It is ubiquitously expressed in many tissues and cell types. The C-terminus of the EST1A protein contains a PilT N-terminus (PIN) domain. This structure for this domain has been determined by X-ray crystallography. SMG6 functions to bind single-stranded DNA in telomere maintenance and single-stranded RNA in nonsense-mediated mRNA decay (NMD). The SMG6 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

SMG5 Protein-coding gene in the species Homo sapiens

Protein SMG5 is a protein that in humans is encoded by the SMG5 gene. This protein contains a PIN domain that appears to have mutated the residues in the active site.

DCP1A Protein found in humans

mRNA-decapping enzyme 1A is a protein that in humans is encoded by the DCP1A gene.

SMG7 Protein-coding gene in the species Homo sapiens

Protein SMG7 is a protein that in humans is encoded by the SMG7 gene.

DCP1B Protein found in humans

mRNA-decapping enzyme 1B is a protein that in humans is encoded by the DCP1B gene.

Decapping complex Eukaryotic protein complex that removes the 5 cap on mRNA

The mRNA decapping complex is a protein complex in eukaryotic cells responsible for removal of the 5' cap. The active enzyme of the decapping complex is the bilobed Nudix family enzyme Dcp2, which hydrolyzes 5' cap and releases 7mGDP and a 5'-monophosphorylated mRNA. This decapped mRNA is inhibited for translation and will be degraded by exonucleases. The core decapping complex is conserved in eukaryotes. Dcp2 is activated by Decapping Protein 1 (Dcp1) and in higher eukaryotes joined by the scaffold protein VCS. Together with many other accessory proteins, the decapping complex assembles in P-bodies in the cytoplasm.

mRNA surveillance mechanisms are pathways utilized by organisms to ensure fidelity and quality of messenger RNA (mRNA) molecules. There are a number of surveillance mechanisms present within cells. These mechanisms function at various steps of the mRNA biogenesis pathway to detect and degrade transcripts that have not properly been processed.

Exon junction complex Protein complex assembled on mRNA

An exon junction complex (EJC) is a protein complex which forms on a pre-messenger RNA strand at the junction of two exons which have been joined together during RNA splicing. The EJC has major influences on translation, surveillance and localization of the spliced mRNA. It is first deposited onto mRNA during splicing and is then transported into the cytoplasm. There it plays a major role in post-transcriptional regulation of mRNA. It is believed that exon junction complexes provide a position-specific memory of the splicing event. The EJC consists of a stable heterotetramer core, which serves as a binding platform for other factors necessary for the mRNA pathway. The core of the EJC contains the protein eukaryotic initiation factor 4A-III bound to an adenosine triphosphate (ATP) analog, as well as the additional proteins Magoh and Y14. The binding of these proteins to nuclear speckled domains has been measured recently and it may be regulated by PI3K/AKT/mTOR signaling pathways. In order for the binding of the complex to the mRNA to occur, the eIF4AIII factor is inhibited, stopping the hydrolysis of ATP. This recognizes EJC as an ATP dependent complex. EJC also interacts with a large number of additional proteins; most notably SR proteins. These interactions are suggested to be important for mRNA compaction. The role of EJC in mRNA export is controversial.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000125351 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036572 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE (Jan 2001). "Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4)". Mol Cell Biol. 21 (1): 209–23. doi:10.1128/MCB.21.1.209-223.2001. PMC   88795 . PMID   11113196.
  6. 1 2 3 Lykke-Andersen J, Shu MD, Steitz JA (Feb 2001). "Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon". Cell. 103 (7): 1121–31. doi: 10.1016/S0092-8674(00)00214-2 . PMID   11163187.
  7. 1 2 "Entrez Gene: UPF3B UPF3 regulator of nonsense transcripts homolog B (yeast)".
  8. Lehner, Ben; Sanderson Christopher M (Jul 2004). "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–23. doi:10.1101/gr.2122004. ISSN   1088-9051. PMC   442147 . PMID   15231747.
  9. 1 2 Lejeune, Fabrice; Li Xiaojie; Maquat Lynne E (Sep 2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities". Mol. Cell. 12 (3): 675–87. doi: 10.1016/S1097-2765(03)00349-6 . ISSN   1097-2765. PMID   14527413.
  10. Lykke-Andersen, Jens (Dec 2002). "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay". Mol. Cell. Biol. 22 (23): 8114–21. doi:10.1128/MCB.22.23.8114-8121.2002. ISSN   0270-7306. PMC   134073 . PMID   12417715.
  11. Schell, Thomas; Köcher Thomas; Wilm Matthias; Seraphin Bertrand; Kulozik Andreas E; Hentze Matthias W (Aug 2003). "Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells". Biochem. J. 373 (Pt 3): 775–83. doi:10.1042/BJ20021920. ISSN   0264-6021. PMC   1223536 . PMID   12723973.

Further reading