Nuclear cap-binding protein subunit 1

UniProt Q09161 Organism Homo sapiens Gene CBP80, NCBP, NCBP1

Also known as: CBP80, NCBP, NCBP1

Function

Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability.

Classification

Family (Pfam): PF02854 MIF4G, PF09088 MIF4G_like, PF09090 MIF4G_like_2
InterPro: ARM-type_fold, CBP80, MIF4G-like_typ-1, MIF4G-like_typ-2, MIF4G-like_typ-3
Functional cluster: Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 18

1H2T X-ray 2.10A
1H2U X-ray 2.40A
1H2V X-ray 2.00A
1H6K X-ray 2.00A
1N52 X-ray 2.11A
1N54 X-ray 2.72A
3FEX X-ray 3.55A
3FEY X-ray 2.20A
5OO6 X-ray 2.80A
5OOB X-ray 2.79A
6D0Y X-ray 2.68A
7ABG EM 7.80A
… and 6 more

A predicted model is available from AlphaFold.

Gene Ontology · 36

Drugs targeting this protein · 1

OBEFAZIMOD modulator

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Nuclear cap-binding protein subunit 2 13 shared papers
CBP80/20-dependent translation initiation factor 1 shared papers
CBP80/20-dependent translation initiation factor 1 shared papers
Nuclear cap-binding protein subunit 2 1 shared papers
Nuclear RNA export factor 1 1 shared papers
Serrate RNA effector molecule homolog 3 shared papers
Nuclear exosome regulator NRDE2 1 shared papers
Polymerase delta-interacting protein 3 1 shared papers
Importin subunit alpha-4 2 shared papers
Serine/arginine repetitive matrix protein 1 1 shared papers
Eukaryotic initiation factor 4A-III 3 shared papers
Nuclear cap-binding protein subunit 3 1 shared papers

Literature · 43 cited papers

The PNUTS phosphatase complex controls transcription pause release. Mol. Cell · 2024
Dominant KPNA3 Mutations Cause Infantile-Onset Hereditary Spastic Paraplegia. Ann. Neurol. · 2021
NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction. Genes Dev. · 2019
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
Identification of a nuclear exosome decay pathway for processed transcripts. Mol. Cell · 2016
The m(6)A methyltransferase METTL3 promotes translation in human cancer cells. Mol. Cell · 2016
mRNA export through an additional cap-binding complex consisting of NCBP1 and NCBP3. Nat. Commun. · 2015
The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex. Cell Rep. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
… and 31 more in the literature graph

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