NXF1

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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
RNA expression pattern
PBB GE NXF1 208922 s at fs.png

PBB GE NXF1 220934 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006362
NM_001081491

NM_001276704
NM_016813

RefSeq (protein)

NP_001074960
NP_006353

NP_058093.2
NP_001263633
NP_058093

Location (UCSC) Chr 11: 62.79 – 62.81 Mb Chr 19: 8.76 – 8.77 Mb
PubMed search [1] [2]
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.[3][4]

Function[edit]

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.[4][5] 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.[6] 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.[7][8]

Interactions[edit]

NXF1 has been shown to interact with TNPO2,[9] MAGOH,[10] U2 small nuclear RNA auxiliary factor 1,[11] DHX9,[12] HuD[13] and NUP214.[14][15]

Tap protein[edit]

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
Symbol TAP_C
Pfam PF03943
Pfam clan CL0214
InterPro IPR005637
SCOP 1go5
SUPERFAMILY 1go5

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

  • vertebrate mRNA export factor TAP or nuclear RNA export factor 1 (NXF1).
  • Caenorhabditis elegans nuclear RNA export factor 1 (nxf-1).
  • yeast mRNA export factor MEX67. Members of the NXF family have a modular structure. A nuclear localization sequence and a noncanonical RNA recognition motif (RRM) (see PROSITEDOC) followed by four LRR repeats are located in its N-terminal half. The C-terminal half contains a NTF2 domain (see [href="http://expasy.org/prosite/PDOC50177 PROSITEDOC]) followed by a second domain, TAP-C. The TAP-C domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate nuclear shuttling.[16][17]

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.[16][17]

Function[edit]

Nuclear export of mRNAs is mediated by the Tap protein.

Structure[edit]

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.

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ a b Grüter P, Tabernero C, von Kobbe C, et al. (April 1998). "TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus". Mol. Cell. 1 (5): 649–59. doi:10.1016/S1097-2765(00)80065-9. PMID 9660949. 
  5. ^ 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". EMBO J. 18 (9): 2593–609. doi:10.1093/emboj/18.9.2593. PMC 1171339Freely accessible. PMID 10228171. 
  6. ^ "Entrez Gene: NXF1 nuclear RNA export factor 1". 
  7. ^ 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". Nat. Genet. 35 (3): 221–8. doi:10.1038/ng1247. PMC 2756099Freely accessible. PMID 14517553. 
  8. ^ Concepcion D, Flores-García L, Hamilton BA (May 2009). Frankel, Wayne N., ed. "Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing". PLoS Genet. 5 (5): e1000484. doi:10.1371/journal.pgen.1000484. PMC 2674570Freely accessible. PMID 19436707. 
  9. ^ Shamsher, Monee K; Ploski Jonathan; Radu Aurelian (October 2002). "Karyopherin beta 2B participates in mRNA export from the nucleus". Proc. Natl. Acad. Sci. U.S.A. United States. 99 (22): 14195–9. doi:10.1073/pnas.212518199. ISSN 0027-8424. PMC 137860Freely accessible. PMID 12384575. 
  10. ^ Kataoka, N; Diem M D; Kim V N; 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". EMBO J. England. 20 (22): 6424–33. doi:10.1093/emboj/20.22.6424. ISSN 0261-4189. PMC 125744Freely accessible. PMID 11707413. 
  11. ^ Zolotukhin, Andrei S; Tan Wei; Bear Jenifer; Smulevitch Sergey; Felber Barbara K (February 2002). "U2AF participates in the binding of TAP (NXF1) to mRNA". J. Biol. Chem. United States. 277 (6): 3935–42. doi:10.1074/jbc.M107598200. ISSN 0021-9258. PMID 11724776. 
  12. ^ 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". J. Biol. Chem. UNITED STATES. 275 (42): 32694–700. doi:10.1074/jbc.M003933200. ISSN 0021-9258. PMID 10924507. 
  13. ^ Saito, Kuniaki; Fujiwara Toshinobu; Katahira Jun; Inoue Kunio; Sakamoto Hiroshi (August 2004). "TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD". Biochem. Biophys. Res. Commun. United States. 321 (2): 291–7. doi:10.1016/j.bbrc.2004.06.140. ISSN 0006-291X. PMID 15358174. 
  14. ^ Herold, A; Suyama M; Rodrigues J P; Braun I C; 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". Mol. Cell. Biol. UNITED STATES. 20 (23): 8996–9008. doi:10.1128/MCB.20.23.8996-9008.2000. ISSN 0270-7306. PMC 86553Freely accessible. PMID 11073998. 
  15. ^ Schmitt, I; Gerace L (November 2001). "In vitro analysis of nuclear transport mediated by the C-terminal shuttle domain of Tap". J. Biol. Chem. United States. 276 (45): 42355–63. doi:10.1074/jbc.M103916200. ISSN 0021-9258. PMID 11551912. 
  16. ^ a b Grant RP, Hurt E, Neuhaus D, Stewart M (April 2002). "Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1". Nat. Struct. Biol. 9 (4): 247–51. doi:10.1038/nsb773. PMID 11875519. 
  17. ^ a b 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 Rep. 1 (1): 53–8. doi:10.1038/sj.embor.embor627. PMC 1083685Freely accessible. PMID 11256625.