Review on RANBP9 (RAN binding protein 9), with data on DNA, on the protein encoded, and where the gene is implicated

Baek, KH

Suresh, B

Atlas of Genetics and Cytogenetics in Oncology and Haematology

KH Baek

B Suresh

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RANBP9 (RAN binding protein 9)

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Gene Section 
Short Communication 
 
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(8)  549 
INIST-CNRS 
 
OPEN ACCESS JOURNAL 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
RANBP9 (RAN binding protein 9) 
Kwang-Hyun Baek, Bharathi Suresh 
CHA Stem Cell Institute, CHA University, 606-16 Yeoksam 1-Dong, Gangnam-Gu, Seoul 135-081, Korea 
(KHB), Department of Biomedical Science, CHA University, CHA General Hospital, Seoul 135-081, 
Republic of Korea (BS) 
 
Published in Atlas Database: March 2012 
Online updated version : http://AtlasGeneticsOncology.org/Genes/RANBP9ID42040ch6p23.html 
DOI: 10.4267/2042/47488 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Other names: BPM-L, BPM90, RANBPM, RanBP7 
HGNC (Hugo): RANBP9 
Location: 6p23 
Local order: It is located on chromosome 6. 
DNA/RNA 
Description 
Constists of 14 exons. 
Transcription 
The coding region of the gene starts from exon 1 to 
exon 14 (60th bps to 2249th bps). The length of the 
transcript is 2190 bps. 
Pseudogene 
No known pseudogenes. 
Protein 
Description 
RanBPM was originally identified as a centrosomal 55 
kDa protein and is involved in microtubule nucleation 
at the centrosome (Nakamura et al., 1998). 
A later work by the same group revealed that the full-
length RanBPM encodes for 729 amino acids and its 
molecular weight is 90 kDa (Nishitani et al., 2001). 
RanBPM protein contains multiple conserved domains 
which provide potential protein-protein interaction sites 
such as an N-terminus proline rich domain (PRD), a 
splA and Ryr (SPRY) domain (212-333 aa), a 
lissencephaly type-I-like homology (LisH) motif (365-
397 aa), a carboxy terminal to LisH (CTLH) motif 
(403-460 aa), and a CT11-RanBPM (CRA) motif (615-
717 aa) at the C terminus of RanBPM (Murrin and 
Talbot, 2007). These domains play a significant role in 
interaction of RanBPM with a wide range of 
transmembrane and intracellular proteins. 
Expression 
RanBPM is ubiquitously expressed in human and 
murine cell lines and tissues of kidney, uterus, ovary, 
bladder, spleen, thymus, brain, skeletal muscle, lung, 
prostate, testes, small intestine, colon and peripheral 
blood lymphocytes (Rao et al., 2002; Wang et al., 
2002).  
In contrast, reduced expression was observed in cancer 
cells and in several human tumor tissues. 
 
 
 
RANBP9 (RAN binding protein 9) Baek KH, Suresh B 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(8)  550 
 
 
Localisation 
RanBPM is localized in the nucleus, cytoplasm, plasma 
membrane and cell juctions (Nishitani et al., 2001; 
Umeda et al., 2003; Denti et al., 2004; Chang et al., 
2010). 
Function 
The direct binding of RanBPM with p73α, results in the 
nuclear translocation of cytoplasmic RanBPM. 
RanBPM is involved in the stabilization of p73 protein 
by preventing its degradation through the ubiquitin-
proteasomal pathway and increases its proapoptotic 
function (Kramer et al., 2005). Expression of RanBPM 
augments T-type Ca2+ currents in HEK293/Cav3.1 
cells (Kim et al., 2009). RanBPM was found to abolish 
the inhibitory effect of PKC on Cav3.1 currents, 
suggesting a key role of RanBPM in Cav3.1 channel-
mediated signaling pathways. RanBPM interacts with 
brain-specific protein p42IP4, and modulates the 
p42IP4 function to regulate synaptic plasticity, actin 
cytoskeleton remodeling and mitogen-activated protein 
kinase cascade (Haase et al., 2008). 
RanBPM also exhibits negative regulation. It binds 
with Mu opioid receptor (MOP), and inhibits the 
agonist-induced receptor internalization without 
altering MOP signaling through adenylyl cyclase, 
suggesting the regulatory effect of RanBPM on MOP 
activity in mammalian cells (Talbot et al., 2009). 
CD39, a prototypic member of the NTPDase family, 
forms a complex with RanBPM (Wu et al., 2006). This 
association substantially down-regulates the NTPDase 
activity of CD39. 
RanBPM also acts as a ligand for the Rho-GEF domain 
(Bowman et al., 2008). RanBPM along with Rho-GEF 
domain of obscurin regulates the assembly of titin 
during the formation of the Z-disk and A/I junction, 
showing a vital role of RanBPM in myofibrillogenesis. 
RanBPM stimulates the transcriptional activity of 
different proteins. RanBPM interacts with androgen 
receptor (AR) (Rao et al., 2002). AR belongs to a large 
steroid receptor family which also includes 
glucocorticoid (GR), progesterone, and 
mineralocorticoid receptors. RanBPM was found to 
enhance AR transactivation in a ligand-dependent 
fashion. Similar results were observed with GR 
activity, whereas the estrogen receptor activity remains 
unaffected. Furthermore, RanBPM was found to 
enhance the activity of thyroid hormone receptors 
(TRs), a member of nuclear receptor superfamily in a 
ligand-independent manner (Poirier et al., 2006), which 
confirms the selective action of RanBPM on receptors 
activity. 
Expression of RanBPM influences the activity of Rta, 
which activates the transcription of Epstein-Barr virus 
(EBV) lytic genes and the lytic cycle, indicating a new 
role of RanBPM as a viral protein regulator. 
Sumoylation of Rta enhances its activity to complete 
the EBV lytic development in an efficient way (Chang 
et al., 2008). RanBPM promotes Rta sumoylation by 
interacting with Ubc9, which states the participation of 
RanBPM in EBV lytic activation. 
RanBPM interacts with several proteins which are 
involved in neurological function. By interacting with 
PlexinA receptor, RanBPM mediates Semaphorin 3A 
signaling which is involved in axonal growth (Togashi 
et al., 2006). It also interacts with calbindin D28K 
(Lutz et al., 2003) and TAF4 to regulate neuritogenesis 
in neural stem cells (Brunkhorst et al., 2005). 
Expression of RanBPM in primary neurons decreased 
L1-dependent neurite outgrowth and extension (Cheng 
et al., 2005). RanBPM showed high expression in the 
Kenyon cells of the larval mushroom body (MB), and 
its expression is sufficient to rescue all behavioral 
phenotypes (Scantlebury et al., 2010). By performing 
genetic epistasis experiments, authors observed the 
participation of RanBPM with the FMRP (Fragile X 
Mental Retardation Protein) in the development of 
neuromuscular junction. Citron kinase (CITK) plays an 
important role in neurogenic mitoses. RanBPM 
potentially interacts with CITK and plays a novel role 
in the progression of neocortical precursors through M-
phase at the ventricular surface (Chang et al., 2010). 
Homology 
Human RanBPM shows 90% nucleotide homology 
with mouse RanBPM. 
Implicated in 
Various cancers 
Note 
RanBPM binds to and modulates the function of a wide 
range of proteins. RanBPM interacts with oncoprotein 
Mgl-1 (Suresh et al., 2010) in mammalian cultured 
cells and modulates stability of Mgl-1 and functionally 
extends the half-life of Mgl-1 by preventing its protein 
turnover through the ubiquitin-proteasomal pathway. 
Furthermore, the overexpression of RanBPM inhibits 
RANBP9 (RAN binding protein 9) Baek KH, Suresh B 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(8)  551 
the activity of Mgl-1 both in cell migration and colony 
formation assays, which reveal the novel role of 
RanBPM as an activator of tumor suppressor. 
References 
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overexpressed, a novel centrosomal protein, RanBPM, causes 
ectopic microtubule nucleation similar to gamma-tubulin. J Cell 
Biol. 1998 Nov 16;143(4):1041-52 
Nishitani H, Hirose E, Uchimura Y, Nakamura M, Umeda M, 
Nishii K, Mori N, Nishimoto T. Full-sized RanBPM cDNA 
encodes a protein possessing a long stretch of proline and 
glutamine within the N-terminal region, comprising a large 
protein complex. Gene. 2001 Jul 11;272(1-2):25-33 
Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, 
Rennie PS. RanBPM, a nuclear protein that interacts with and 
regulates transcriptional activity of androgen receptor and 
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Wang D, Li Z, Messing EM, Wu G. Activation of Ras/Erk 
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J Biol Chem. 2010 Nov 12;285(46):35340-9 
This article should be referenced as such: 
Baek KH, Suresh B. RANBP9 (RAN binding protein 9). Atlas 
Genet Cytogenet Oncol Haematol. 2012; 16(8):549-551. 


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RANBP9 (RAN binding protein 9)

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