{PDOC50177}
{PS50177; NTF2_DOMAIN}
{BEGIN}
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* Nuclear transport factor 2 domain profile *
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Nucleocytoplasmic  transport  is  mediated  by large supramolecular structures
that  span the nuclear envelope called nuclear pore complexes (NPC). Classical
import pathway involves proteins containing nuclear localisation signal (NLS).
This  transport signal is recognized in the cytosol by importin alpha. Binding
of  the resulting complex to the cytoplasmic fibrils of the NPC is mediated by
the  cytosolic  factor  importin  beta.  From  their, the substrate-alpha-beta
transport  complex move to a central NPC region, where it pass through a gated
channel [1,2].

This  nuclear import as well as the export pathway are dependent on the GTPase
cycle  of  Ran  protein,  a  Ras-related  GTPase.  RanGDP  is generated in the
cytoplasm by RanGTPase-activating protein and Ran is recharged with GTP in the
nucleus  by  the  RCC1  factor  (see <PDOC00544>). RanGTP is exported from the
nucleus  bound  to  importin proteins and must be recycled back to the nucleus
for  new exchange. This recycling step of Ran is mediated by Nuclear transport
factor 2 (NTF2) [3,4]. This small protein specifically binds to RanGDP and the
nuclear pore  proteins containing phenylalanine-glycine (XFXFG) repeats [5,6].
These interactions  are  required for the transport of RanGDP into the nucleus
[6].

Structurally [7],  NTF2  forms  an  alpha-beta barrel that opens at one end to
form a  distinctive  hydrophobic  cavity.  The  crystal  structure  of NTF2 in
complex with  RanGDP  [8]  shows  that  the  interaction  is  mediated  by the
hydrophobic cavity  of  NTF2  and  the  putative  switch  II  loop of Ran. The
contribution of  the switch II loop certainly accounts for the ability of NTF2
to discriminate between GDP and GTP-bound forms of Ran.

The following proteins contain a region similar to NTF2:

 - Eukaryotic  NXF  proteins [9]. These are nuclear mRNA export factors. These
   proteins contain, in addition to a NTF2 domain, a number of leucine-rich
   repeats and a UBA domain.
 - Eukaryotic  NXT1/NXT2  proteins  [9].  These  proteins  are  stimulators of
   protein export for  NES-containing  proteins.  The also play a role in mRNA
   nuclear export. They heterodimerize with NFX proteins. In contrast to NTF2,
   NXT1 and NXT2 preferentially bind RanGTP.
 - eukaryotic  Ras-GTPase-activating  protein (GAP)-binding proteins (G3BP's).
   These proteins contain one NTF2 domain and one RRM (see <PDOC00030>).

We developed a profile for NTF2 that spans the complete domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2001 / First entry.

[ 1] Mattaj I.W., Englmeier L.
     "Nucleocytoplasmic transport: the soluble phase."
     Annu. Rev. Biochem. 67:265-306(1998).
     PubMed=9759490; DOI=10.1146/annurev.biochem.67.1.265
[ 2] Melchior F., Gerace L.
     "Two-way trafficking with Ran."
     Trends Cell Biol. 8:175-179(1998).
     PubMed=9695834
[ 3] Nehrbass U., Blobel G.
     "Role of the nuclear transport factor p10 in nuclear import."
     Science 272:120-122(1996).
     PubMed=8600522
[ 4] Smith A., Brownawell A., Macara I.G.
     "Nuclear import of Ran is mediated by the transport factor NTF2."
     Curr. Biol. 8:1403-1406(1998).
     PubMed=9889103
[ 5] Clarkson W.D., Kent H.M., Stewart M.
     "Separate binding sites on nuclear transport factor 2 (NTF2) for
     GDP-Ran and the phenylalanine-rich repeat regions of nucleoporins p62
     and Nsp1p."
     J. Mol. Biol. 263:517-524(1996).
     PubMed=8918934
[ 6] Bayliss R., Ribbeck K., Akin D., Kent H.M., Feldherr C.M., Gorlich D.,
     Stewart M.
     "Interaction between NTF2 and xFxFG-containing nucleoporins is
     required to mediate nuclear import of RanGDP."
     J. Mol. Biol. 293:579-593(1999).
     PubMed=10543952; DOI=10.1006/jmbi.1999.3166
[ 7] Bullock T.L., Clarkson W.D., Kent H.M., Stewart M.
     "The 1.6 angstroms resolution crystal structure of nuclear transport
     factor 2 (NTF2)."
     J. Mol. Biol. 260:422-431(1996).
     PubMed=8757804
[ 8] Stewart M., Kent H.M., McCoy A.J.
     "Structural basis for molecular recognition between nuclear transport
     factor 2 (NTF2) and the GDP-bound form of the Ras-family GTPase Ran."
     J. Mol. Biol. 277:635-646(1998).
     PubMed=9533885
[ 9] Herold A., Suyama M., Rodrigues J.P., Braun I.C., Kutay U.,
     Carmo-Fonseca M., Bork P., Izaurralde E.
     "TAP (NXF1) belongs to a multigene family of putative RNA export
     factors with a conserved modular architecture."
     Mol. Cell. Biol. 20:8996-9008(2000).
     PubMed=11073998

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