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GNB2L1 (guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1)

Identity

Other namesGnb2-rs1
H12.3
HLC-7
PIG21 (proliferation-inducing gene 21)
RACK1 (Receptor for activated kinase C)
lung cancer oncogene 7
protein homologous to chicken B complex protein, guanine nucleotide binding
HGNC (Hugo) GNB2L1
LocusID (NCBI) 10399
Location 5q35.3
Location_base_pair Starts at 180663928 and ends at 180670906 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note Aberrations on 5q35.3 are reported to be associated with asbestos-related lung cancer. 5q35.3 also displays high frequency of deletions in non small lung carcinoma.

DNA/RNA

Description The gene spans approximatively 6.9 Kb. Orientation minus strand. Number of exons: 10.
Transcription The length of GNB2L1 transcript is 951bp.

Protein

Description GNB2L1 encodes a cytosolic protein with a molecular mass of approximatively 35 kDa (317 amino acids). The protein has seven internal Trp-Asp 40 (WD40 domain) repeats. The WD40 repeats of RACK1/GNB2L1 are predicted to form a seven-bladed propeller structure, where each blade is composed of a four-stranded anti-parallel beta-sheet. The highly conserved WD repeat sequence of RACK1/GNB2L1 is found in a number of eukaryotic proteins and is implicated in a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly.
Expression GNB2L1 is ubiquitously expressed in the tissues of higher mammals and humans including brain, liver, and spleen.
Localisation GNB2L1 is a cytosolic protein.
Function GNB2L1 was originally identified as an anchoring protein for protein kinase C beta (PKCbeta), which it stabilises in the active state and anchors to membranes or functional sites. However, evidence has accumulated to support a central role of RACK1/GNB2L1 in critical biological responses. In addition to binding specifically to the active form of PKCbeta isoforms, GNB2L1 also interacts with several other important signaling proteins including the Src kinase family, integrin beta1, integrin beta2, integrin beta3 and integrin beta5, beta-spectrin and dynamin, RasGAP, the androgen receptor , insulin-like growth factor 1 receptor (IGF-1r), Epstein-Barr virus trans-activator protein BZLF1, p73 and pRB.
This suggests that GNB2L1 may act as an anchor or adaptor protein, recruiting other proteins to various transmembrane receptors, providing a platform for protein-protein interactions and acting as the focus for several cell-signaling pathways. Accordingly, a number of cellular functions have been attributed to GNB2L1, e.g. in cell growth, adhesion, protrusion and chemotactic migration.
GNB2L1 might also have an effect on brain function; a reduction in GNB2L1 levels by around 50% has been reported in the brains of aged rats compared with adult or middle aged rat brains. GNB2L1 is also reported to be involved in number of functions in the nervous system. These include neurite growth, dendritic transport, glutamatergic and dopaminergic neurotransmissions and functioning of GABAA receptors.
In addition, up-regulation of GNB2L1 in lymphocytes results in suppression of apoptosis, indicating that it also plays an important role in the regulation of apoptosis. It is also reported that GNB2L1 inhibits the effects of adenovirus E1a on yeast, Saos osteosarcoma and HeLa cells, including the induction of apoptosis.
In addition, GNB2L1 over-expression was reported to protect PC-12 cell survival on withdrawal of Nerve Growth Factor.
Homology GNB2L1 is homologous to the G protein beta subunit, having 42% identity with many conserved amino acid substitutions.

Mutations

Note Mutations in the GNB2L1 gene have not been found in 274 samples from somatic cancer. However, GNB2L1 is reported to be up-regulated in angiogenesis and in human carcinomas.

Implicated in

Entity Brain pathologies and ageing
Disease Changes in GNB2L1 levels were found in a number of brain pathologies and during ageing. GNB2L1 levels were significantly decreased in the cortex of patients with Down Syndrome, all of who develop Alzheimer's disease as young adults. Association of GNB2L1 with PKC was put forward as a putative cause of the increase in PKC activity observed in the frontal cortex of subjects with bipolar disorder.
  
Entity Angiogenesis and tumor growth
Oncogenesis GNB2L1 might contribute to angiogenesis and tumor growth, since it was shown to be up-regulated during angiogenesis in vitro and in vivo, and was also expressed in tumor angiogenesis. GNB2L1 expression was higher in human non-small cell lung and colon carcinomas than in the corresponding normal tissues.
  

External links

Nomenclature
HGNC (Hugo)GNB2L1   4399
Cards
AtlasGNB2L1ID43285ch5q35
Entrez_Gene (NCBI)GNB2L1  10399  guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1
GeneCards (Weizmann)GNB2L1
Ensembl hg19 (Hinxton)ENSG00000204628 [Gene_View]  chr5:180663928-180670906 [Contig_View]  GNB2L1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000204628 [Gene_View]  chr5:180663928-180670906 [Contig_View]  GNB2L1 [Vega]
ICGC DataPortalENSG00000204628
cBioPortalGNB2L1
AceView (NCBI)GNB2L1
Genatlas (Paris)GNB2L1
WikiGenes10399
SOURCE (Princeton)GNB2L1
Genomic and cartography
GoldenPath hg19 (UCSC)GNB2L1  -     chr5:180663928-180670906 -  5q35.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GNB2L1  -     5q35.3   [Description]    (hg38-Dec_2013)
EnsemblGNB2L1 - 5q35.3 [CytoView hg19]  GNB2L1 - 5q35.3 [CytoView hg38]
Mapping of homologs : NCBIGNB2L1 [Mapview hg19]  GNB2L1 [Mapview hg38]
OMIM176981   
Gene and transcription
Genbank (Entrez)AK095666 AK222488 AK301029 AK301468 AK303316
RefSeq transcript (Entrez)NM_006098
RefSeq genomic (Entrez)AC_000137 NC_000005 NC_018916 NT_023133 NW_001838967 NW_004929325
Consensus coding sequences : CCDS (NCBI)GNB2L1
Cluster EST : UnigeneHs.5662 [ NCBI ]
CGAP (NCI)Hs.5662
Alternative Splicing : Fast-db (Paris)GSHG0025354
Alternative Splicing GalleryENSG00000204628
Gene ExpressionGNB2L1 [ NCBI-GEO ]     GNB2L1 [ SEEK ]   GNB2L1 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP63244 (Uniprot)
NextProtP63244  [Medical]
With graphics : InterProP63244
Splice isoforms : SwissVarP63244 (Swissvar)
Domaine pattern : Prosite (Expaxy)WD_REPEATS_1 (PS00678)    WD_REPEATS_2 (PS50082)    WD_REPEATS_REGION (PS50294)   
Domains : Interpro (EBI)G-protein_beta_WD-40_rep    WD40/YVTN_repeat-like_dom    WD40_repeat    WD40_repeat_CS    WD40_repeat_dom   
Related proteins : CluSTrP63244
Domain families : Pfam (Sanger)WD40 (PF00400)   
Domain families : Pfam (NCBI)pfam00400   
Domain families : Smart (EMBL)WD40 (SM00320)  
DMDM Disease mutations10399
Blocks (Seattle)P63244
PDB (SRS)3J3A    4AOW   
PDB (PDBSum)3J3A    4AOW   
PDB (IMB)3J3A    4AOW   
PDB (RSDB)3J3A    4AOW   
Human Protein AtlasENSG00000204628
Peptide AtlasP63244
HPRD01503
IPIIPI00848226   IPI00910917   IPI00964025   IPI00964259   IPI00964491   IPI00964790   IPI00966041   IPI00967322   IPI00965671   IPI00966034   IPI00967577   IPI00967585   IPI00966111   IPI01018069   IPI00964877   IPI00965503   IPI00965193   IPI00910221   IPI00967345   IPI00964515   IPI00964313   IPI00965459   IPI00967792   IPI00966368   
Protein Interaction databases
DIP (DOE-UCLA)P63244
IntAct (EBI)P63244
FunCoupENSG00000204628
BioGRIDGNB2L1
IntegromeDBGNB2L1
STRING (EMBL)GNB2L1
Ontologies - Pathways
QuickGOP63244
Ontology : AmiGOphagocytic cup  positive regulation of protein phosphorylation  protein kinase C binding  receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  cytoskeleton  activation of cysteine-type endopeptidase activity involved in apoptotic process  cell cycle  gastrulation  ion channel inhibitor activity  cysteine-type endopeptidase activator activity involved in apoptotic process  negative regulation of gene expression  small ribosomal subunit  viral process  negative regulation of translation  enzyme binding  protein phosphatase binding  negative regulation of Wnt signaling pathway  protein tyrosine kinase inhibitor activity  negative regulation of cell growth  positive regulation of cell migration  dendrite  midbody  positive regulation of cAMP catabolic process  receptor tyrosine kinase binding  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  positive regulation of protein homooligomerization  positive regulation of protein homooligomerization  regulation of protein localization  protein complex scaffold  SH2 domain binding  protein homodimerization activity  neuronal cell body  positive regulation of apoptotic process  positive regulation of apoptotic process  perikaryon  negative regulation of neuron apoptotic process  positive regulation of GTPase activity  poly(A) RNA binding  perinuclear region of cytoplasm  rhythmic process  negative regulation of phagocytosis  regulation of cell division  positive regulation of cyclic-nucleotide phosphodiesterase activity  regulation of cell cycle  negative regulation of protein kinase B signaling  positive regulation of mitochondrial depolarization  negative regulation of protein tyrosine kinase activity  extracellular vesicular exosome  regulation of establishment of protein localization to plasma membrane  negative regulation of hydrogen peroxide-mediated programmed cell death  regulation of establishment of cell polarity  positive regulation of gastrulation  positive regulation of intrinsic apoptotic signaling pathway  
Ontology : EGO-EBIphagocytic cup  positive regulation of protein phosphorylation  protein kinase C binding  receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  cytoskeleton  activation of cysteine-type endopeptidase activity involved in apoptotic process  cell cycle  gastrulation  ion channel inhibitor activity  cysteine-type endopeptidase activator activity involved in apoptotic process  negative regulation of gene expression  small ribosomal subunit  viral process  negative regulation of translation  enzyme binding  protein phosphatase binding  negative regulation of Wnt signaling pathway  protein tyrosine kinase inhibitor activity  negative regulation of cell growth  positive regulation of cell migration  dendrite  midbody  positive regulation of cAMP catabolic process  receptor tyrosine kinase binding  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  positive regulation of protein homooligomerization  positive regulation of protein homooligomerization  regulation of protein localization  protein complex scaffold  SH2 domain binding  protein homodimerization activity  neuronal cell body  positive regulation of apoptotic process  positive regulation of apoptotic process  perikaryon  negative regulation of neuron apoptotic process  positive regulation of GTPase activity  poly(A) RNA binding  perinuclear region of cytoplasm  rhythmic process  negative regulation of phagocytosis  regulation of cell division  positive regulation of cyclic-nucleotide phosphodiesterase activity  regulation of cell cycle  negative regulation of protein kinase B signaling  positive regulation of mitochondrial depolarization  negative regulation of protein tyrosine kinase activity  extracellular vesicular exosome  regulation of establishment of protein localization to plasma membrane  negative regulation of hydrogen peroxide-mediated programmed cell death  regulation of establishment of cell polarity  positive regulation of gastrulation  positive regulation of intrinsic apoptotic signaling pathway  
Pathways : KEGGMeasles   
Protein Interaction DatabaseGNB2L1
DoCM (Curated mutations)GNB2L1
Wikipedia pathwaysGNB2L1
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerGNB2L1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GNB2L1
dbVarGNB2L1
ClinVarGNB2L1
1000_GenomesGNB2L1 
Exome Variant ServerGNB2L1
SNP (GeneSNP Utah)GNB2L1
SNP : HGBaseGNB2L1
Genetic variants : HAPMAPGNB2L1
Genomic VariantsGNB2L1  GNB2L1 [DGVbeta]
Mutations
ICGC Data PortalENSG00000204628 
Somatic Mutations in Cancer : COSMICGNB2L1 
CONAN: Copy Number AnalysisGNB2L1 
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
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)5:180663928-180670906
Mutations and Diseases : HGMDGNB2L1
OMIM176981   
MedgenGNB2L1
NextProtP63244 [Medical]
GENETestsGNB2L1
Disease Genetic AssociationGNB2L1
Huge Navigator GNB2L1 [HugePedia]  GNB2L1 [HugeCancerGEM]
snp3D : Map Gene to Disease10399
DGIdb (Drug Gene Interaction db)GNB2L1
General knowledge
Homologs : HomoloGeneGNB2L1
Homology/Alignments : Family Browser (UCSC)GNB2L1
Phylogenetic Trees/Animal Genes : TreeFamGNB2L1
Chemical/Protein Interactions : CTD10399
Chemical/Pharm GKB GenePA28779
Clinical trialGNB2L1
Cancer Resource (Charite)ENSG00000204628
Other databases
Probes
Litterature
PubMed231 Pubmed reference(s) in Entrez
CoreMineGNB2L1
GoPubMedGNB2L1
iHOPGNB2L1

Bibliography

Identification of intracellular receptor proteins for activated protein kinase C.
Mochly-Rosen D, Khaner H, Lopez J
Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (9) : 3997-4000.
PMID 1850844
 
The WD-40 repeat.
van der Voorn L, Ploegh HL
FEBS letters. 1992 ; 307 (2) : 131-134.
PMID 1644165
 
Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins.
Ron D, Chen CH, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D
Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (3) : 839-843.
PMID 8302854
 
Interaction of protein kinase C with RACK1, a receptor for activated C-kinase: a role in beta protein kinase C mediated signal transduction.
Mochly-Rosen D, Smith BL, Chen CH, Disatnik MH, Ron D
Biochemical Society transactions. 1995 ; 23 (3) : 596-600.
PMID 8566424
 
Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex.
Pascale A, Fortino I, Govoni S, Trabucchi M, Wetsel WC, Battaini F
Journal of neurochemistry. 1996 ; 67 (6) : 2471-2477.
PMID 8931480
 
The role of anchoring protein RACK1 in PKC activation in the ageing rat brain.
Battaini F, Pascale A, Paoletti R, Govoni S
Trends in neurosciences. 1997 ; 20 (9) : 410-415.
PMID 9292970
 
Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit.
Liliental J, Chang DD
The Journal of biological chemistry. 1998 ; 273 (4) : 2379-2383.
PMID 9442085
 
Anchoring proteins for protein kinase C: a means for isozyme selectivity.
Mochly-Rosen D, Gordon AS
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1998 ; 12 (1) : 35-42.
PMID 9438408
 
The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1.
Baumann M, Gires O, Kolch W, Mischak H, Zeidler R, Pich D, Hammerschmidt W
European journal of biochemistry / FEBS. 2000 ; 267 (12) : 3891-3901.
PMID 10849009
 
RACK1 is up-regulated in angiogenesis and human carcinomas.
Berns H, Humar R, Hengerer B, Kiefer FN, Battegay EJ
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (15) : 2549-2558.
PMID 11099474
 
Frequent loss of heterozygosity on chromosome 5 in non-small cell lung carcinoma.
Mendes-da-Silva P, Moreira A, Duro-da-Costa J, Matias D, Monteiro C
Molecular pathology : MP. 2000 ; 53 (4) : 184-187.
PMID 11040940
 
The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration.
Buensuceso CS, Woodside D, Huff JL, Plopper GE, O'Toole TE
Journal of cell science. 2001 ; 114 (Pt 9) : 1691-1698.
PMID 11309199
 
Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder.
Wang H, Friedman E
Biological psychiatry. 2001 ; 50 (5) : 364-370.
PMID 11543740
 
RACK1: a novel substrate for the Src protein-tyrosine kinase.
Chang BY, Harte RA, Cartwright CA
Oncogene. 2002 ; 21 (50) : 7619-7629.
PMID 12400005
 
Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21).
Peyrl A, Weitzdoerfer R, Gulesserian T, Fountoulakis M, Lubec G
Electrophoresis. 2002 ; 23 (1) : 152-157.
PMID 11824616
 
Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB.
Ozaki T, Watanabe K, Nakagawa T, Miyazaki K, Takahashi M, Nakagawara A
Oncogene. 2003 ; 22 (21) : 3231-3242.
PMID 12761493
 
The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway.
Rigas AC, Ozanne DM, Neal DE, Robson CN
The Journal of biological chemistry. 2003 ; 278 (46) : 46087-46093.
PMID 12958311
 
Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis.
Mourtada-Maarabouni M, Kirkham L, Farzaneh F, Williams GT
Journal of leukocyte biology. 2005 ; 78 (2) : 503-514.
PMID 15870214
 
RACK1 has the nerve to act: structure meets function in the nervous system.
Sklan EH, Podoly E, Soreq H
Progress in neurobiology. 2006 ; 78 (2) : 117-134.
PMID 16457939
 
Identification of specific gene copy number changes in asbestos-related lung cancer.
Nymark P, Wikman H, Ruosaari S, Hollmˆ©n J, Vanhala E, Karjalainen A, Anttila S, Knuutila S
Cancer research. 2006 ; 66 (11) : 5737-5743.
PMID 16740712
 
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Contributor(s)

Written09-2007Mirna Mourtada-Maarabouni
School of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom

Citation

This paper should be referenced as such :
Mourtada-Maarabouni, M
GNB2L1 (guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):149-150.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/GNB2L1ID43285ch5q35.html

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