NXF1

Last updated
NXF1
PDB 1fo1 EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NXF1 , MEX67, TAP, nuclear RNA export factor 1
External IDs OMIM: 602647 MGI: 1858330 HomoloGene: 38176 GeneCards: NXF1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006362
NM_001081491

NM_001276704
NM_016813

RefSeq (protein)

NP_001074960
NP_006353

NP_001263633
NP_058093

Location (UCSC) Chr 11: 62.79 – 62.81 Mb Chr 19: 8.73 – 8.75 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Nuclear RNA export factor 1, also known as NXF1 or TAP, is a protein which in humans is encoded by the NXF1 gene. [5] [6]

Function

This gene is one member of a family of nuclear RNA export factor genes. Common domain features of this family are a noncanonical RNP-type RNA-binding domain (RBD), 4 leucine-rich repeats (LRRs), a nuclear transport factor 2 (NTF2)-like domain that allows heterodimerization with NTF2-related export protein-1 (NXT1), and a ubiquitin-associated domain that mediates interactions with nucleoporins. Alternative splicing results in transcript variants. The LRRs and NTF2-like domains are required for export activity. The encoded protein of this gene shuttles between the nucleus and the cytoplasm and binds in vivo to poly(A)+ RNA. It is the vertebrate homologue of the yeast protein Mex67p. [6] [7] The encoded protein overcomes the mRNA export block caused by the presence of saturating amounts of CTE (constitutive transport element) RNA of type D retroviruses. [8] A variant allele of the homologous Nxf1 gene in mice suppresses a class of mutations caused by integration of an endogenous retrovirus (intracisternal A particle) into an intron. [9] [10]

Interactions

NXF1 has been shown to interact with TNPO2, [11] MAGOH, [12] U2 small nuclear RNA auxiliary factor 1, [13] DHX9, [14] HuD [15] and NUP214. [16] [17]

Tap protein

In molecular biology, another name for the protein NXF1 is TAP. In particular this entry focuses on the C-terminal domain, which also contains the UBA (protein domain).

TAP_C
PDB 1oai EBI.jpg
complex between tap uba domain and fxfg nucleoporin peptide
Identifiers
SymbolTAP_C
Pfam PF03943
Pfam clan CL0214
InterPro IPR005637
SCOP2 1go5 / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

This entry contains the NXF family of shuttling transport receptors for nuclear export of mRNA, which include:

The Tap-C domain is made of four alpha helices packed against each other. The arrangement of helices 1, 2 and 3 is similar to that seen in a UBA fold. and is joined to the next module by flexible 12-residue Pro-rich linker. [18] [19]

Function

Nuclear export of mRNAs is mediated by the Tap protein.

Structure

Tap can form a multimeric complex with itself and with other members of the NXF family. Three functional domains of Tap have been well characterized: the RNA-binding domain, the Nuclear Transport Factor 2 (NTF2)-like domain, and the ubiquitin-associated (UBA) domain.

Related Research Articles

<span class="mw-page-title-main">Nuclear pore</span> Openings in nuclear envelope of eukaryotic cells

A nuclear pore is a channel as part of the nuclear pore complex (NPC), a large protein complex found in the nuclear envelope in eukaryotic cells, enveloping the cell nucleus containing DNA, which facilitates the selective membrane transport of various molecules across the membrane.

Transporter associated with antigen processing (TAP) protein complex belongs to the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules.

<span class="mw-page-title-main">Nuclear pore glycoprotein p62</span> Protein-coding gene in the species Homo sapiens

Nuclear pore glycoprotein p62 is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by modification that involve addition of N-acetylglucosamine residues, followed by association with other complex proteins. In humans it is encoded by the NUP62 gene.

<span class="mw-page-title-main">KPNB1</span> Protein-coding gene in the species Homo sapiens

Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.

<span class="mw-page-title-main">NUP98</span> Protein-coding gene in the species Homo sapiens

Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the NUP98 gene.

<span class="mw-page-title-main">RBM8A</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">Nucleoporin 153</span> Protein-coding gene in the species Homo sapiens

Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.

<span class="mw-page-title-main">Transportin 1</span> Protein-coding gene in the species Homo sapiens

Transportin-1 is a protein that in humans is encoded by the TNPO1 gene.

<span class="mw-page-title-main">Nucleoporin 214</span> Protein-coding gene in the species Homo sapiens

Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.

<span class="mw-page-title-main">RNPS1</span> Protein-coding gene in the species Homo sapiens

RNA-binding protein with serine-rich domain 1 is a protein that in humans is encoded by the RNPS1 gene.

<span class="mw-page-title-main">AGFG1</span> Protein-coding gene in the species Homo sapiens

Arf-GAP domain and FG repeat-containing protein 1 is a protein that in humans is encoded by the AGFG1 gene.

<span class="mw-page-title-main">RAE1</span> Protein-coding gene in the species Homo sapiens

mRNA export factor is a protein that in humans is encoded by the RAE1 gene.

<span class="mw-page-title-main">ALYREF</span> Protein-coding gene in the species Homo sapiens

Aly/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene.

<span class="mw-page-title-main">MAGOH</span> Protein-coding gene in the species Homo sapiens

Protein mago nashi homolog is a protein that in humans is encoded by the MAGOH gene.

<span class="mw-page-title-main">NXT1</span> Protein-coding gene in the species Homo sapiens

NTF2-related export protein 1 is a protein that in humans is encoded by the NXT1 gene.

<span class="mw-page-title-main">NUPL2</span> Protein-coding gene in the species Homo sapiens

Nucleoporin-like 2 is a protein that in humans is encoded by the NUPL2 gene.

<span class="mw-page-title-main">TNPO2</span> Protein-coding gene in the species Homo sapiens

Transportin-2 is a protein that in humans is encoded by the TNPO2 gene.

<span class="mw-page-title-main">NXF2</span> Protein-coding gene in the species Homo sapiens

Nuclear RNA export factor 2 is a protein that in humans is encoded by the NXF2 gene.

<span class="mw-page-title-main">Exon junction complex</span> 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, localization of the spliced mRNA, and m6A methylation. 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.

The TREX (TRanscription-EXport) complex is a conserved eukaryotic multi-protein complex that couples mRNA transcription and nuclear export. The TREX complex travels across transcribed genes with RNA polymerase II. TREX binds mRNA and recruits transport proteins NXF1 and NXT1, which shuttle the mRNA out of the nucleus. The TREX complex plays an important role in genome stability and neurodegenerative diseases.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000162231 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000010097 - 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. Yoon DW, Lee H, Seol W, DeMaria M, Rosenzweig M, Jung JU (May 1997). "Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation". Immunity. 6 (5): 571–82. doi: 10.1016/S1074-7613(00)80345-3 . PMID   9175835.
  6. 1 2 Grüter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E (April 1998). "TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus". Molecular Cell. 1 (5): 649–59. doi: 10.1016/S1097-2765(00)80065-9 . PMID   9660949.
  7. Katahira J, Strässer K, Podtelejnikov A, Mann M, Jung JU, Hurt E (May 1999). "The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human". The EMBO Journal. 18 (9): 2593–609. doi:10.1093/emboj/18.9.2593. PMC   1171339 . PMID   10228171.
  8. "Entrez Gene: NXF1 nuclear RNA export factor 1".
  9. Floyd JA, Gold DA, Concepcion D, Poon TH, Wang X, Keithley E, Chen D, Ward EJ, Chinn SB, Friedman RA, Yu HT, Moriwaki K, Shiroishi T, Hamilton BA (November 2003). "A natural allele of Nxf1 suppresses retrovirus insertional mutations". Nature Genetics. 35 (3): 221–8. doi:10.1038/ng1247. PMC   2756099 . PMID   14517553.
  10. Concepcion D, Flores-García L, Hamilton BA (May 2009). "Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing". PLOS Genetics. 5 (5): e1000484. doi: 10.1371/journal.pgen.1000484 . PMC   2674570 . PMID   19436707.
  11. Shamsher MK, Ploski J, Radu A (October 2002). "Karyopherin beta 2B participates in mRNA export from the nucleus". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14195–9. Bibcode:2002PNAS...9914195S. doi: 10.1073/pnas.212518199 . PMC   137860 . PMID   12384575.
  12. Kataoka N, Diem MD, Kim VN, Yong J, Dreyfuss G (November 2001). "Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex". The EMBO Journal. 20 (22): 6424–33. doi:10.1093/emboj/20.22.6424. PMC   125744 . PMID   11707413.
  13. Zolotukhin AS, Tan W, Bear J, Smulevitch S, Felber BK (February 2002). "U2AF participates in the binding of TAP (NXF1) to mRNA". The Journal of Biological Chemistry. 277 (6): 3935–42. doi: 10.1074/jbc.M107598200 . PMID   11724776.
  14. Tang H, Wong-Staal F (October 2000). "Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus". The Journal of Biological Chemistry. 275 (42): 32694–700. doi: 10.1074/jbc.M003933200 . PMID   10924507.
  15. Saito K, Fujiwara T, Katahira J, Inoue K, Sakamoto H (August 2004). "TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD". Biochemical and Biophysical Research Communications. 321 (2): 291–7. doi:10.1016/j.bbrc.2004.06.140. PMID   15358174.
  16. Herold A, Suyama M, Rodrigues JP, Braun IC, Kutay U, Carmo-Fonseca M, Bork P, Izaurralde E (December 2000). "TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture". Molecular and Cellular Biology. 20 (23): 8996–9008. doi:10.1128/MCB.20.23.8996-9008.2000. PMC   86553 . PMID   11073998.
  17. Schmitt I, Gerace L (November 2001). "In vitro analysis of nuclear transport mediated by the C-terminal shuttle domain of Tap". The Journal of Biological Chemistry. 276 (45): 42355–63. doi: 10.1074/jbc.M103916200 . PMID   11551912.
  18. 1 2 Grant RP, Hurt E, Neuhaus D, Stewart M (April 2002). "Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1". Nature Structural Biology. 9 (4): 247–51. doi:10.1038/nsb773. PMID   11875519. S2CID   11338341.
  19. 1 2 Suyama M, Doerks T, Braun IC, Sattler M, Izaurralde E, Bork P (July 2000). "Prediction of structural domains of TAP reveals details of its interaction with p15 and nucleoporins". EMBO Reports. 1 (1): 53–8. doi:10.1093/embo-reports/kvd009. PMC   1083685 . PMID   11256625.