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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 α. Binding of the resulting complex to the cytoplasmic fibrils of the NPC is mediated by the cytosolic factor importin β. From their, the substrate-α-β 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 α-β 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.

December 2001 / First entry.

PROSITE method (with tools and information) covered by this documentation:

NTF2_DOMAIN, PS50177; Nuclear transport factor 2 domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS50177 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50177 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50177 • Scan Swiss-Prot/TrEMBL entries against PS50177 • view ligand binding statistics

Matching PDB structures: 1A2K 1AR0 1ASK 1GY5 ... [ALL]

1	Authors	Mattaj I.W., Englmeier L.
	Title	Nucleocytoplasmic transport: the soluble phase.
	Source	Annu. Rev. Biochem. 67:265-306(1998).
	PubMed ID	9759490
	DOI	10.1146/annurev.biochem.67.1.265

2	Authors	Melchior F., Gerace L.
	Title	Two-way trafficking with Ran.
	Source	Trends Cell Biol. 8:175-179(1998).
	PubMed ID	9695834

3	Authors	Nehrbass U., Blobel G.
	Title	Role of the nuclear transport factor p10 in nuclear import.
	Source	Science 272:120-122(1996).
	PubMed ID	8600522

4	Authors	Smith A., Brownawell A., Macara I.G.
	Title	Nuclear import of Ran is mediated by the transport factor NTF2.
	Source	Curr. Biol. 8:1403-1406(1998).
	PubMed ID	9889103

5	Authors	Clarkson W.D., Kent H.M., Stewart M.
	Title	Separate binding sites on nuclear transport factor 2 (NTF2) for GDP-Ran and the phenylalanine-rich repeat regions of nucleoporins p62 and Nsp1p.
	Source	J. Mol. Biol. 263:517-524(1996).
	PubMed ID	8918934

6	Authors	Bayliss R., Ribbeck K., Akin D., Kent H.M., Feldherr C.M., Gorlich D., Stewart M.
	Title	Interaction between NTF2 and xFxFG-containing nucleoporins is required to mediate nuclear import of RanGDP.
	Source	J. Mol. Biol. 293:579-593(1999).
	PubMed ID	10543952
	DOI	10.1006/jmbi.1999.3166

7	Authors	Bullock T.L., Clarkson W.D., Kent H.M., Stewart M.
	Title	The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
	Source	J. Mol. Biol. 260:422-431(1996).
	PubMed ID	8757804

8	Authors	Stewart M., Kent H.M., McCoy A.J.
	Title	Structural basis for molecular recognition between nuclear transport factor 2 (NTF2) and the GDP-bound form of the Ras-family GTPase Ran.
	Source	J. Mol. Biol. 277:635-646(1998).
	PubMed ID	9533885

9	Authors	Herold A., Suyama M., Rodrigues J.P., Braun I.C., 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.
	Source	Mol. Cell. Biol. 20:8996-9008(2000).
	PubMed ID	11073998

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