Nuclear cap-binding protein subunit 2

Function

Component of the cap-binding complex (CBC), which binds co-transcriptionally 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, thereby being 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, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus.

Classification

Family (Pfam)

PF00076 RRM_1

InterPro

NCBP2, NCBP2_RRM, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom

Functional cluster

Serine/Threonine Protein Kinases

Experimental structures · PDB · 18

• 1H2T X-ray 2.15A
• 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 · 31

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005846 nuclear cap binding complex
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0034518 RNA cap binding complex
• GO:0003677 DNA binding
• GO:0003729 mRNA binding
• GO:0000340 RNA 7-methylguanosine cap binding
• GO:0003723 RNA binding
• GO:0000339 RNA cap binding
• GO:0017069 snRNA binding
• GO:0000380 alternative mRNA splicing, via spliceosome
• GO:0002191 cap-dependent translational initiation
• GO:0008334 histone mRNA metabolic process
• GO:0035195 miRNA-mediated post-transcriptional gene silencing
• GO:0031124 mRNA 3'-end processing
• GO:0045292 mRNA cis splicing, via spliceosome
• GO:0006406 mRNA export from nucleus
• GO:0016071 mRNA metabolic process
• GO:0000398 mRNA splicing, via spliceosome
• GO:0042789 mRNA transcription by RNA polymerase II
• GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
• GO:0031442 positive regulation of mRNA 3'-end processing
• GO:0046833 positive regulation of RNA export from nucleus
• GO:0032968 positive regulation of transcription elongation by RNA polymerase II
• GO:0031053 primary miRNA processing
• GO:0006446 regulation of translational initiation
• GO:0035194 regulatory ncRNA-mediated post-transcriptional gene silencing
• GO:0008380 RNA splicing
• GO:0006408 snRNA export from nucleus

Drugs targeting this protein · 1

• OBEFAZIMOD modulator

Related proteins · sequence + function similarity

• Nuclear cap-binding protein subunit 2 0.99
• Nuclear cap-binding protein subunit 2 0.99
• Nuclear cap-binding protein subunit 2 0.98
• Nuclear cap-binding protein subunit 2 0.97
• Nuclear cap-binding protein subunit 2 0.96
• Nuclear cap-binding protein subunit 2 0.96
• Nuclear cap-binding protein subunit 2 0.95
• Nuclear cap-binding protein subunit 2 0.95
• Nuclear cap-binding protein subunit 2 0.94
• Nuclear cap-binding protein subunit 2 0.94
• Nuclear cap-binding protein subunit 2 0.94
• Nuclear cap-binding protein subunit 2 0.94

Co-cited proteins · studied together in the literature

• Nuclear cap-binding protein subunit 1 13 shared papers
• Nuclear cap-binding protein subunit 2 1 shared papers
• Importin subunit alpha-4 2 shared papers
• Nuclear cap-binding protein subunit 3 1 shared papers
• Nuclear cap-binding protein subunit 3 1 shared papers
• Ribonuclease 3 1 shared papers
• Nuclear cap-binding protein subunit 2 1 shared papers
• Serrate RNA effector molecule homolog 2 shared papers
• Regulator of chromosome condensation 1 shared papers
• Nucleolar RNA helicase 2 1 shared papers
• Serrate RNA effector molecule homolog 1 shared papers
• Nuclear cap-binding protein subunit 1 1 shared papers

Literature · 25 cited papers

• Dominant KPNA3 Mutations Cause Infantile-Onset Hereditary Spastic Paraplegia. Ann. Neurol. · 2021
• mRNA export through an additional cap-binding complex consisting of NCBP1 and NCBP3. Nat. Commun. · 2015
• Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol. Cell. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell · 2009
• NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep. · 2008
• Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat. Struct. Mol. Biol. · 2007
• ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science · 2007
• The interaction between cap-binding complex and RNA export factor is required for intronless mRNA export. J. Biol. Chem. · 2007
• … and 13 more in the literature graph