RANBP9 (RAN binding protein 9)

2012-03-01   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)

Identity

HGNC
LOCATION
6p23
LOCUSID
ALIAS
BPM-L,BPM90,RANBPM,RanBP7
FUSION GENES

DNA/RNA

Atlas Image

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.

Proteins

Atlas Image

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.

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

Entity name
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 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.

Bibliography

Pubmed IDLast YearTitleAuthors
185796862008The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9.Bowman AL et al
184551882008Enhancement of transactivation activity of Rta of Epstein-Barr virus by RanBPM.Chang LK et al
197901052010RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.Chang Y et al
160001622005RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation.Cheng L et al
147220852004RanBPM is a phosphoprotein that associates with the plasma membrane and interacts with the integrin LFA-1.Denti S et al
182986632008RanBPM, a novel interaction partner of the brain-specific protein p42IP4/centaurin alpha-1.Haase A et al
188013352009Modulation of Ca(v)3.1 T-type Ca2+ channels by the ran binding protein RanBPM.Kim T et al
155580192005Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells.Kramer S et al
126840612003Calbindin D28K interacts with Ran-binding protein M: identification of interacting domains by NMR spectroscopy.Lutz W et al
180408642007RanBPM, a scaffolding protein in the immune and nervous systems.Murrin LC et al
98177601998When overexpressed, a novel centrosomal protein, RanBPM, causes ectopic microtubule nucleation similar to gamma-tubulin.Nakamura M et al
114705072001Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex.Nishitani H et al
165957022006Identification and characterization of RanBPM, a novel coactivator of thyroid hormone receptors.Poirier MB et al
123619452002RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor.Rao MA et al
204988422010The Drosophila gene RanBPM functions in the mushroom body to regulate larval behavior.Scantlebury N et al
208293632010Stability and function of mammalian lethal giant larvae-1 oncoprotein are regulated by the scaffolding protein RanBPM.Suresh B et al
197889132009Regulation of mu opioid receptor internalization by the scaffold protein RanBPM.Talbot JN et al
166726722006RanBPM contributes to Semaphorin3A signaling through plexin-A receptors.Togashi H et al
125595652003A novel nuclear protein, Twa1, and Muskelin comprise a complex with RanBPM.Umeda M et al
121476922002Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM.Wang D et al
164784412006RanBPM associates with CD39 and modulates ecto-nucleotidase activity.Wu Y et al

Other Information

Locus ID:

NCBI: 10048
MIM: 603854
HGNC: 13727
Ensembl: ENSG00000010017

Variants:

dbSNP: 10048
ClinVar: 10048
TCGA: ENSG00000010017
COSMIC: RANBP9

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000010017ENST00000011619Q96S59
ENSG00000010017ENST00000011619A0A024QZW3

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
L1CAM interactionsREACTOMER-HSA-373760
RET signalingREACTOMER-HSA-8853659
Signaling by METREACTOMER-HSA-6806834
MET activates RAS signalingREACTOMER-HSA-8851805

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
174671962007RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8alpha and ARMC8beta are components of the CTLH complex.48
121476922002Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM.47
192517052009Novel role of RanBP9 in BACE1 processing of amyloid precursor protein and amyloid beta peptide generation.44
147220852004RanBPM is a phosphoprotein that associates with the plasma membrane and interacts with the integrin LFA-1.42
180408642007RanBPM, a scaffolding protein in the immune and nervous systems.37
187109242008Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation.35
155580192005Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells.33
197295162010A fragment of the scaffolding protein RanBP9 is increased in Alzheimer's disease brains and strongly potentiates amyloid-beta peptide generation.33
164784412006RanBPM associates with CD39 and modulates ecto-nucleotidase activity.27
123619452002RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor.26

Citation

Kwang-Hyun Baek ; Bharathi Suresh

RANBP9 (RAN binding protein 9)

Atlas Genet Cytogenet Oncol Haematol. 2012-03-01

Online version: http://atlasgeneticsoncology.org/gene/42040/ranbp9-(ran-binding-protein-9)