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RANBP9 (RAN binding protein 9)

Identity

Other namesBPM-L
BPM90
RANBPM
RanBP7
HGNC (Hugo) RANBP9
LocusID (NCBI) 10048
Location 6p23
Location_base_pair Starts at 13621730 and ends at 13711796 bp from pter ( according to hg19-Feb_2009)  [Mapping]
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.
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 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.
  

External links

Nomenclature
HGNC (Hugo)RANBP9   13727
Cards
AtlasRANBP9ID42040ch6p23
Entrez_Gene (NCBI)RANBP9  10048  RAN binding protein 9
GeneCards (Weizmann)RANBP9
Ensembl (Hinxton)ENSG00000010017 [Gene_View]  chr6:13621730-13711796 [Contig_View]  RANBP9 [Vega]
ICGC DataPortalENSG00000010017
AceView (NCBI)RANBP9
Genatlas (Paris)RANBP9
WikiGenes10048
SOURCE (Princeton)NM_005493
Genomic and cartography
GoldenPath (UCSC)RANBP9  -  6p23   chr6:13621730-13711796 -  6p23   [Description]    (hg19-Feb_2009)
EnsemblRANBP9 - 6p23 [CytoView]
Mapping of homologs : NCBIRANBP9 [Mapview]
OMIM603854   
Gene and transcription
Genbank (Entrez)AB008515 AB055311 AF064606 AF306510 AK313334
RefSeq transcript (Entrez)NM_005493
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NT_007592 NW_001838973 NW_004929326
Consensus coding sequences : CCDS (NCBI)RANBP9
Cluster EST : UnigeneHs.708182 [ NCBI ]
CGAP (NCI)Hs.708182
Alternative Splicing : Fast-db (Paris)GSHG0026318
Alternative Splicing GalleryENSG00000010017
Gene ExpressionRANBP9 [ NCBI-GEO ]     RANBP9 [ SEEK ]   RANBP9 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96S59 (Uniprot)
NextProtQ96S59  [Medical]
With graphics : InterProQ96S59
Splice isoforms : SwissVarQ96S59 (Swissvar)
Domaine pattern : Prosite (Expaxy)B302_SPRY (PS50188)    CTLH (PS50897)    LISH (PS50896)   
Domains : Interpro (EBI)B30.2/SPRY    ConA-like_lec_gl_sf    CRA_dom    CTLH/CRA    CTLH_C    LisH_dimerisation    LisH_dimerisation_subgr    SPla/RYanodine_receptor_subgr    SPRY_rcpt   
Related proteins : CluSTrQ96S59
Domain families : Pfam (Sanger)CLTH (PF10607)    LisH (PF08513)    SPRY (PF00622)   
Domain families : Pfam (NCBI)pfam10607    pfam08513    pfam00622   
Domain families : Smart (EMBL)CRA (SM00757)  CTLH (SM00668)  LisH (SM00667)  SPRY (SM00449)  
DMDM Disease mutations10048
Blocks (Seattle)Q96S59
Human Protein AtlasENSG00000010017
Peptide AtlasQ96S59
HPRD04835
IPIIPI00465275   IPI00554545   IPI00513912   
Protein Interaction databases
DIP (DOE-UCLA)Q96S59
IntAct (EBI)Q96S59
FunCoupENSG00000010017
BioGRIDRANBP9
IntegromeDBRANBP9
STRING (EMBL)RANBP9
Ontologies - Pathways
QuickGOQ96S59
Ontology : AmiGOprotein binding  nucleus  cytosol  microtubule associated complex  protein complex assembly  microtubule nucleation  axon guidance  Ran GTPase binding  enzyme binding  
Ontology : EGO-EBIprotein binding  nucleus  cytosol  microtubule associated complex  protein complex assembly  microtubule nucleation  axon guidance  Ran GTPase binding  enzyme binding  
REACTOMEQ96S59 [protein]
REACTOME PathwaysREACT_111045 Developmental Biology [pathway]
Protein Interaction DatabaseRANBP9
Wikipedia pathwaysRANBP9
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)RANBP9
SNP (GeneSNP Utah)RANBP9
SNP : HGBaseRANBP9
Genetic variants : HAPMAPRANBP9
1000_GenomesRANBP9 
ICGC programENSG00000010017 
CONAN: Copy Number AnalysisRANBP9 
Somatic Mutations in Cancer : COSMICRANBP9 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)6:13621730-13711796
Mutations and Diseases : HGMDRANBP9
OMIM603854   
MedgenRANBP9
GENETestsRANBP9
Disease Genetic AssociationRANBP9
Huge Navigator RANBP9 [HugePedia]  RANBP9 [HugeCancerGEM]
Genomic VariantsRANBP9  RANBP9 [DGVbeta]
Exome VariantRANBP9
dbVarRANBP9
ClinVarRANBP9
snp3D : Map Gene to Disease10048
General knowledge
Homologs : HomoloGeneRANBP9
Homology/Alignments : Family Browser (UCSC)RANBP9
Phylogenetic Trees/Animal Genes : TreeFamRANBP9
Chemical/Protein Interactions : CTD10048
Chemical/Pharm GKB GenePA34215
Clinical trialRANBP9
Cancer Resource (Charite)ENSG00000010017
Other databases
Probes
Litterature
PubMed83 Pubmed reference(s) in Entrez
CoreMineRANBP9
GoPubMedRANBP9
iHOPRANBP9

Bibliography

When overexpressed, a novel centrosomal protein, RanBPM, causes ectopic microtubule nucleation similar to gamma-tubulin.
Nakamura M, Masuda H, Horii J, Kuma K, Yokoyama N, Ohba T, Nishitani H, Miyata T, Tanaka M, Nishimoto T.
J Cell Biol. 1998 Nov 16;143(4):1041-52.
PMID 9817760
 
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.
Nishitani H, Hirose E, Uchimura Y, Nakamura M, Umeda M, Nishii K, Mori N, Nishimoto T.
Gene. 2001 Jul 11;272(1-2):25-33.
PMID 11470507
 
RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor.
Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, Rennie PS.
J Biol Chem. 2002 Dec 13;277(50):48020-7. Epub 2002 Oct 1.
PMID 12361945
 
Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM.
Wang D, Li Z, Messing EM, Wu G.
J Biol Chem. 2002 Sep 27;277(39):36216-22. Epub 2002 Jul 29.
PMID 12147692
 
Calbindin D28K interacts with Ran-binding protein M: identification of interacting domains by NMR spectroscopy.
Lutz W, Frank EM, Craig TA, Thompson R, Venters RA, Kojetin D, Cavanagh J, Kumar R.
Biochem Biophys Res Commun. 2003 Apr 18;303(4):1186-92.
PMID 12684061
 
A novel nuclear protein, Twa1, and Muskelin comprise a complex with RanBPM.
Umeda M, Nishitani H, Nishimoto T.
Gene. 2003 Jan 16;303:47-54.
PMID 12559565
 
RanBPM is a phosphoprotein that associates with the plasma membrane and interacts with the integrin LFA-1.
Denti S, Sirri A, Cheli A, Rogge L, Innamorati G, Putignano S, Fabbri M, Pardi R, Bianchi E.
J Biol Chem. 2004 Mar 26;279(13):13027-34. Epub 2004 Jan 13.
PMID 14722085
 
RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation.
Cheng L, Lemmon S, Lemmon V.
J Neurochem. 2005 Aug;94(4):1102-10. Epub 2005 Jul 5.
PMID 16000162
 
Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells.
Kramer S, Ozaki T, Miyazaki K, Kato C, Hanamoto T, Nakagawara A.
Oncogene. 2005 Jan 27;24(5):938-44.
PMID 15558019
 
Identification and characterization of RanBPM, a novel coactivator of thyroid hormone receptors.
Poirier MB, Laflamme L, Langlois MF.
J Mol Endocrinol. 2006 Apr;36(2):313-25.
PMID 16595702
 
RanBPM contributes to Semaphorin3A signaling through plexin-A receptors.
Togashi H, Schmidt EF, Strittmatter SM.
J Neurosci. 2006 May 3;26(18):4961-9.
PMID 16672672
 
RanBPM associates with CD39 and modulates ecto-nucleotidase activity.
Wu Y, Sun X, Kaczmarek E, Dwyer KM, Bianchi E, Usheva A, Robson SC.
Biochem J. 2006 May 15;396(1):23-30.
PMID 16478441
 
RanBPM, a scaffolding protein in the immune and nervous systems.
Murrin LC, Talbot JN.
J Neuroimmune Pharmacol. 2007 Sep;2(3):290-5. Epub 2007 Jun 28. (REVIEW)
PMID 18040864
 
The 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, Catino DH, Strong JC, Randall WR, Kontrogianni-Konstantopoulos A, Bloch RJ.
Mol Biol Cell. 2008 Sep;19(9):3782-92. Epub 2008 Jun 25.
PMID 18579686
 
Enhancement of transactivation activity of Rta of Epstein-Barr virus by RanBPM.
Chang LK, Liu ST, Kuo CW, Wang WH, Chuang JY, Bianchi E, Hong YR.
J Mol Biol. 2008 May 30;379(2):231-42. Epub 2008 Apr 10.
PMID 18455188
 
RanBPM, a novel interaction partner of the brain-specific protein p42IP4/centaurin alpha-1.
Haase A, Nordmann C, Sedehizade F, Borrmann C, Reiser G.
J Neurochem. 2008 Jun 1;105(6):2237-48.
PMID 18298663
 
Modulation of Ca(v)3.1 T-type Ca2+ channels by the ran binding protein RanBPM.
Kim T, Kim S, Yun HM, Chung KC, Han YS, Shin HS, Rhim H.
Biochem Biophys Res Commun. 2009 Jan 2;378(1):15-20. Epub 2008 Sep 16.
PMID 18801335
 
Regulation of mu opioid receptor internalization by the scaffold protein RanBPM.
Talbot JN, Skifter DA, Bianchi E, Monaghan DT, Toews ML, Murrin LC.
Neurosci Lett. 2009 Dec 11;466(3):154-8. Epub 2009 Sep 27.
PMID 19788913
 
RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.
Chang Y, Paramasivam M, Girgenti MJ, Walikonis RS, Bianchi E, LoTurco JJ.
Dev Neurobiol. 2010 Jan;70(1):1-15.
PMID 19790105
 
The Drosophila gene RanBPM functions in the mushroom body to regulate larval behavior.
Scantlebury N, Zhao XL, Rodriguez Moncalvo VG, Camiletti A, Zahanova S, Dineen A, Xin JH, Campos AR.
PLoS One. 2010 May 14;5(5):e10652.
PMID 20498842
 
Stability and function of mammalian lethal giant larvae-1 oncoprotein are regulated by the scaffolding protein RanBPM.
Suresh B, Ramakrishna S, Kim YS, Kim SM, Kim MS, Baek KH.
J Biol Chem. 2010 Nov 12;285(46):35340-9. Epub 2010 Sep 9.
PMID 20829363
 
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Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2012Kwang-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)

Citation

This paper should be referenced as such :
Baek, KH ; Suresh, B
RANBP9 (RAN binding protein 9)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):549-551.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/RANBP9ID42040ch6p23.html

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indexed on : Sat Nov 8 17:02:56 CET 2014

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