NXF1 — Mediated Wiki

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Nuclear RNA export factor 1''', also known as '''NXF1''' or '''TAP''', is a protein which in humans is encoded by the ''NXF1'' gene.<ref name="pmid9175835">{{cite journal | vauthors = Yoon DW, Lee H, Seol W, DeMaria M, Rosenzweig M, Jung JU | title = Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation | journal = Immunity | volume = 6 | issue = 5 | pages = 571–82 | date = May 1997 | pmid = 9175835 | doi = 10.1016/S1074-7613(00)80345-3 | doi-access = free }}</ref><ref name="pmid9660949">{{cite journal | vauthors = Grüter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E | title = TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus | journal = Molecular Cell | volume = 1 | issue = 5 | pages = 649–59 | date = April 1998 | pmid = 9660949 | doi = 10.1016/S1097-2765(00)80065-9 | doi-access = free }}</ref>

== 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.<ref name="pmid9660949"/><ref name="pmid10228171">{{cite journal | vauthors = Katahira J, Strässer K, Podtelejnikov A, Mann M, Jung JU, Hurt E | title = The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human | journal = The EMBO Journal | volume = 18 | issue = 9 | pages = 2593–609 | date = May 1999 | pmid = 10228171 | pmc = 1171339 | doi = 10.1093/emboj/18.9.2593 }}</ref> 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.<ref>{{cite web | title = Entrez Gene: NXF1 nuclear RNA export factor 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10482}}</ref> 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.<ref name="pmid14517553">{{cite journal | vauthors = 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 | title = A natural allele of Nxf1 suppresses retrovirus insertional mutations | journal = Nature Genetics | volume = 35 | issue = 3 | pages = 221–8 | date = November 2003 | pmid = 14517553 | pmc = 2756099 | doi = 10.1038/ng1247 }}</ref><ref name="pmid19436707">{{cite journal | vauthors = Concepcion D, Flores-García L, Hamilton BA | title = Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing | journal = PLOS Genetics | volume = 5 | issue = 5 | article-number = e1000484 | date = May 2009 | pmid = 19436707 | pmc = 2674570 | doi = 10.1371/journal.pgen.1000484 | doi-access = free }}</ref>

== Interactions ==

NXF1 has been shown to interact with TNPO2,<ref name=pmid12384575>{{cite journal | vauthors = Shamsher MK, Ploski J, Radu A | title = Karyopherin beta 2B participates in mRNA export from the nucleus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 22 | pages = 14195–9 | date = October 2002 | pmid = 12384575 | pmc = 137860 | doi = 10.1073/pnas.212518199 | bibcode = 2002PNAS...9914195S | doi-access = free }}</ref> MAGOH,<ref name=pmid11707413>{{cite journal | vauthors = Kataoka N, Diem MD, Kim VN, Yong J, Dreyfuss G | title = Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex | journal = The EMBO Journal | volume = 20 | issue = 22 | pages = 6424–33 | date = November 2001 | pmid = 11707413 | pmc = 125744 | doi = 10.1093/emboj/20.22.6424 }}</ref> U2 small nuclear RNA auxiliary factor 1,<ref name=pmid11724776>{{cite journal | vauthors = Zolotukhin AS, Tan W, Bear J, Smulevitch S, Felber BK | title = U2AF participates in the binding of TAP (NXF1) to mRNA | journal = The Journal of Biological Chemistry | volume = 277 | issue = 6 | pages = 3935–42 | date = February 2002 | pmid = 11724776 | doi = 10.1074/jbc.M107598200 | doi-access = free }}</ref> DHX9,<ref name=pmid10924507>{{cite journal | vauthors = Tang H, Wong-Staal F | title = Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus | journal = The Journal of Biological Chemistry | volume = 275 | issue = 42 | pages = 32694–700 | date = October 2000 | pmid = 10924507 | doi = 10.1074/jbc.M003933200 | doi-access = free }}</ref> HuD<ref name=pmid15358174>{{cite journal | vauthors = Saito K, Fujiwara T, Katahira J, Inoue K, Sakamoto H | title = TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD | journal = Biochemical and Biophysical Research Communications | volume = 321 | issue = 2 | pages = 291–7 | date = August 2004 | pmid = 15358174 | doi = 10.1016/j.bbrc.2004.06.140 }}</ref> and NUP214.<ref name=pmid11073998>{{cite journal | vauthors = Herold A, Suyama M, Rodrigues JP, Braun IC, Kutay U, Carmo-Fonseca M, Bork P, Izaurralde E | title = TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture | journal = Molecular and Cellular Biology | volume = 20 | issue = 23 | pages = 8996–9008 | date = December 2000 | pmid = 11073998 | pmc = 86553 | doi = 10.1128/MCB.20.23.8996-9008.2000 }}</ref><ref name=pmid11551912>{{cite journal | vauthors = Schmitt I, Gerace L | title = In vitro analysis of nuclear transport mediated by the C-terminal shuttle domain of Tap | journal = The Journal of Biological Chemistry | volume = 276 | issue = 45 | pages = 42355–63 | date = November 2001 | pmid = 11551912 | doi = 10.1074/jbc.M103916200 | doi-access = free }}</ref>

==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).

{{Infobox protein family | Symbol = TAP_C | Name = TAP_C | image = PDB 1oai EBI.jpg | width = | caption = complex between tap uba domain and fxfg nucleoporin peptide | Pfam = PF03943 | Pfam_clan = CL0214 | InterPro = IPR005637 | SMART = | PROSITE = | MEROPS = | SCOP = 1go5 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} 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 [http://expasy.org/prosite/PDOC00030 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.<ref name="pmid11875519">{{cite journal | vauthors = Grant RP, Hurt E, Neuhaus D, Stewart M | title = Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1 | journal = Nature Structural Biology | volume = 9 | issue = 4 | pages = 247–51 | date = April 2002 | pmid = 11875519 | doi = 10.1038/nsb773 | s2cid = 11338341 }}</ref><ref name="pmid11256625">{{cite journal | vauthors = Suyama M, Doerks T, Braun IC, Sattler M, Izaurralde E, Bork P | title = Prediction of structural domains of TAP reveals details of its interaction with p15 and nucleoporins | journal = EMBO Reports | volume = 1 | issue = 1 | pages = 53–8 | date = July 2000 | pmid = 11256625 | pmc = 1083685 | doi = 10.1093/embo-reports/kvd009}}</ref>

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.<ref name="pmid11875519"/><ref name="pmid11256625"/>

== 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.

== References == {{reflist}}

== External links == * [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/Q9UBU9 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Nuclear RNA export factor 1 (NXF1)