RACK1 (receptor for activated C kinase 1)
2007-09-01 Mirna Mourtada-Maarabouni   AffiliationSchool of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom
Identity
HGNC
LOCATION
5q35.3
LOCUSID
ALIAS
GNB2L1,Gnb2-rs1,H12.3,HLC-7,PIG21
FUSION GENES
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.
Proteins
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.
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 name
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 Alzheimers 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 name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9292970 | 1997 | The role of anchoring protein RACK1 in PKC activation in the ageing rat brain. | Battaini F et al |
| 10849009 | 2000 | The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1. | Baumann M et al |
| 11099474 | 2000 | RACK1 is up-regulated in angiogenesis and human carcinomas. | Berns H et al |
| 11309199 | 2001 | The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration. | Buensuceso CS et al |
| 12400005 | 2002 | RACK1: a novel substrate for the Src protein-tyrosine kinase. | Chang BY et al |
| 9442085 | 1998 | Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit. | Liliental J et al |
| 11040940 | 2000 | Frequent loss of heterozygosity on chromosome 5 in non-small cell lung carcinoma. | Mendes-da-Silva P et al |
| 9438408 | 1998 | Anchoring proteins for protein kinase C: a means for isozyme selectivity. | Mochly-Rosen D et al |
| 15870214 | 2005 | Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis. | Mourtada-Maarabouni M et al |
| 16740712 | 2006 | Identification of specific gene copy number changes in asbestos-related lung cancer. | Nymark P et al |
| 12761493 | 2003 | Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB. | Ozaki T et al |
| 8931480 | 1996 | Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex. | Pascale A et al |
| 11824616 | 2002 | Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). | Peyrl A et al |
| 12958311 | 2003 | The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. | Rigas AC et al |
| 8302854 | 1994 | Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. | Ron D et al |
| 16457939 | 2006 | RACK1 has the nerve to act: structure meets function in the nervous system. | Sklan EH et al |
| 11543740 | 2001 | Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. | Wang H et al |
| 1644165 | 1992 | The WD-40 repeat. | van der Voorn L et al |
Other Information
Locus ID:
NCBI: 10399
MIM: 176981
HGNC: 4399
Ensembl: ENSG00000204628
Variants:
dbSNP: 10399
ClinVar: 10399
TCGA: ENSG00000204628
COSMIC: RACK1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37578594 | 2024 | Loss of RACK1 promotes glutamine addiction via activating AKT/mTOR/ASCT2 axis to facilitate tumor growth in gastric cancer. | 3 |
| 38305509 | 2024 | RACK1 promotes the occurrence and progression of cervical carcinoma. | 1 |
| 38315284 | 2024 | OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination. | 0 |
| 37578594 | 2024 | Loss of RACK1 promotes glutamine addiction via activating AKT/mTOR/ASCT2 axis to facilitate tumor growth in gastric cancer. | 3 |
| 38305509 | 2024 | RACK1 promotes the occurrence and progression of cervical carcinoma. | 1 |
| 38315284 | 2024 | OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination. | 0 |
| 36658304 | 2023 | CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability. | 6 |
| 37532135 | 2023 | OTUB1's role in promoting OSCC development by stabilizing RACK1 involves cell proliferation, migration, invasion, and tumor-associated macrophage M1 polarization. | 1 |
| 37820724 | 2023 | Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. | 4 |
| 37823194 | 2023 | Neuropilin 1 promotes unilateral ureteral obstruction-induced renal fibrosis via RACK1 in renal tubular epithelial cells. | 1 |
| 37828084 | 2023 | Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression. | 3 |
| 37848434 | 2023 | RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin. | 2 |
| 38044732 | 2023 | [Expression of RACK1 and EGP40 in oral squamous cell carcinoma and its correlation with clinicopathological features and prognosis]. | 0 |
| 38111057 | 2023 | Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration. | 0 |
| 36658304 | 2023 | CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability. | 6 |
Citation
Mirna Mourtada-Maarabouni
RACK1 (receptor for activated C kinase 1)
Atlas Genet Cytogenet Oncol Haematol. 2007-09-01
Online version: http://atlasgeneticsoncology.org/gene/43285/rack1
