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NXF1

Domain

The minimal CTE binding domain consists of an RNP-type RNA binding domain (RBD) and leucine-rich repeats.

The nucleoporin binding domain consists of a NTF2 domain (also called NTF2-like domain) and a TAP-C domain (also called UBA-like domain). It has 2 nucleoporin-FG-repeats binding sites (one in the NTF2 and the other in the TAP-C domain) which contribute to nucleoporin association and act synergistically to export cellular mRNAs.

The NTF2 domain is functional only in the presence of NXT1 and is essential for the export of mRNA from the nucleus. It inhibits RNA binding activity through an intramolecular interaction with the N-terminal RNA binding domain (RBD); the inhibition is removed by an association with the TREX complex, specifically involving ALYREF/THOC4 and THOC5.

The TAP-C domain mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim. The conserved loop 594-NWD-596 of the TAP-C domain has a critical role in the interaction with nucleoporins.

The leucine-rich repeats are essential for the export of mRNA from the nucleus.

The RNA-binding domain is a non-canonical RNP-type domain.

Function

Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244).

Sequence similarities

Belongs to the NXF family.

Tissue specificity

Expressed ubiquitously.

Cellular localization

  • Nucleus
  • Nucleus
  • Nucleoplasm
  • Nucleus speckle
  • Nucleus
  • Nuclear pore complex
  • Nucleus envelope
  • Cytoplasm
  • Cytoplasm
  • Stress granule
  • Localized predominantly in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex. Shuttles between the nucleus and the cytoplasm. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. The association with the TREX complex seems to occur in regions surrounding nuclear speckles known as perispeckles (PubMed:23826332). Nucleus; nuclear rim (PubMed:25662211).

Alternative names

  • Nuclear RNA export factor 1
  • Tip-associated protein
  • Tip-associating protein
  • mRNA export factor TAP
  • NXF1
  • TAP

Target type

Proteins

Molecular weight

70182Da