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

Written2007-09Mirna Mourtada-Maarabouni
School of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom

(Note : for Links provided by Atlas : click)


Other namesGnb2-rs1
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
LocusID (NCBI) 10399
Atlas_Id 43285
Location 5q35.3  [Link to chromosome band 5q35]
Location_base_pair Starts at and ends at bp from pter
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.


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


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.


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.


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
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
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
RACK1: a novel substrate for the Src protein-tyrosine kinase.
Chang BY, Harte RA, Cartwright CA
Oncogene. 2002 ; 21 (50) : 7619-7629.
PMID 12400005
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
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
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
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
Identification of specific gene copy number changes in asbestos-related lung cancer.
Nymark P, Wikman H, Ruosaari S, Hollmén J, Vanhala E, Karjalainen A, Anttila S, Knuutila S
Cancer research. 2006 ; 66 (11) : 5737-5743.
PMID 16740712
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
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
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
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
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
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
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
The WD-40 repeat.
van der Voorn L, Ploegh HL
FEBS letters. 1992 ; 307 (2) : 131-134.
PMID 1644165


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 journal version : [ pdf ]   [ DOI ]
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External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)10399
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
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