RAN-BINDING PROTEIN 3-LIKE; RANBP3L

Alternative titles; symbols

• RANBP3-LIKE

HGNC Approved Gene Symbol: RANBP3L

Cytogenetic location: 5p13.2 Genomic coordinates (GRCh38): 5:36,246,912-36,301,901 (from NCBI)

▼ Description
Cell signaling via bone morphogenetic proteins (BMPs; see 112264) is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of SMADs (see SMAD1, 601595), which function in the nucleus to transduce BMP signals. RANBP3L acts as a nuclear export factor for dephosphorylated SMADs (Chen et al., 2015).

▼ Cloning and Expression
By searching a database for sequences similar to RANBP3 (603327), Chen et al. (2015) identified human RANBP3L. The deduced 465-amino acid protein has a central RAN (601179)-binding domain (RANBD) that shares 71% identity with the RANBD of RANBP3.

▼ Gene Function
By coimmunoprecipitation of transfected HEK293 cells, Chen et al. (2015) found that RANBP3L bound a RAN-GTP mimetic. Overexpression of RANBP3L blocked BMP-dependent differentiation in mouse cell lines. RAN binding-defective RANBP3L failed to repress BMP-induced gene expression. Conversely, knockdown of Ranbp3l increased BMP-induced differentiation and expression of BMP-dependent genes. In vitro binding assays showed that RANBP3L interacted with BMP-specific SMAD1, SMAD5 (603110), and SMAD8 (SMAD9; 603295). RANBP3L preferentially bound dephosphorylated SMAD1 and SMAD5 in the nuclei of transfected HEK293T cells, and inclusion of PPM1A (606108) enhanced the interactions. Expression of RANBP3L in HeLa cells reduced nuclear SMAD1, and knockdown of RANBP3L or PPM1A resulted in SMAD1 nuclear retention. Knockdown of both RANBP3L and PPM1A enhanced the effect. Mass spectrometric analysis revealed that RANBP3L interacted with many nucleoporins and transport proteins. Chen et al. (2015) concluded that RANBP3L inhibits BMP signaling by functioning as a nuclear export factor for SMADs.

▼ Mapping
Hartz (2015) mapped the RANBP3L gene to chromosome 5p13.2 based on an alignment of the RANBP3L sequence (GenBank AK058151) with the genomic sequence (GRCh38).