RACK1 (GNB2L1)

RACK1 (guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1), also known as GNB2L1, contains 7 WD repeats and belongs to the WD repeat G protein beta family. In the liver, RACK1 is expressed at higher levels in activated hepatic stellate cells than in hepatocytes or Kupffer cells. It is up-regulated in hepatocellular carcinomas and in the adjacent non-tumor liver tissue. RACK1 is involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. It interacts with a wide variety of proteins and plays a role in many cellular processes. GNB2L1 binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. RACK1 may recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. It inhibits the activity of SRC kinases including SRC, LCK and YES1. RACK1 also inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. It enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer.

RACK1 (GNB2L1) Related Areas

Cancer>>Angiogenesis>> RACK1

RACK1 (GNB2L1) Alternative Names

HLC7, Gnb2-rs1, H12.3, HLC-7, PIG21, RACK1, Receptor for Activated C Kinase 1, cell proliferation-inducing gene 21 protein, guanine nucleotide-binding protein subunit beta-2-like 1, guanine nucleotide-binding protein subunit beta-like protein 12.3, human lung cancer oncogene 7 protein, lung cancer oncogene 7, proliferation-inducing gene 21, protein homologous to chicken B complex protein, guanine nucleotide binding, receptor of activated protein kinase C 1 [Homo sapiens]

GB-like, Gnb2-rs1, Rack1, activated protein kinase C receptor, guanine nucleotide binding protein (G protein), beta polypeptide 2 like 1 sequence 1, guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1, guanine nucleotide binding protein related, guanine nucleotide binding protein, beta 2, related sequence 1, guanine nucleotide binding protein, beta-2, related sequence 1, guanine nucleotide-binding protein subunit beta-2-like 1, receptor for activated C kinase, receptor of activated protein kinase C 1 [Mus musculus]

Summaries for RACK1 (GNB2L1)

Wikipedia summary for RACK1 (GNB2L1):

Guanine nucleotide-binding protein subunit beta-2-like 1 is a protein that in humans is encoded by the GNB2L1 gene.

Human RACK1 (GNB2L1) Protein General Information

 

• Protein names: Receptor of activated protein kinase C 1
  Short name=RACK1
• Sequence length: 317 AA.
• Domain: Repeat
  WD repeat
• Sequence similarities: Belongs to the WD repeat G protein beta family.
  Contains 7 WD repeats.
• Post-translational modification: Phosphorylated on Tyr-228 and/or Tyr-246 by SRC. This is required for binding to SRC.
• Subunit structure: Component of the small (40S) ribosomal subunit . Exists as a monomer and also forms oligomers. Binds SLC9A3R1. Forms a ternary complex with TRIM63 and PRKCE. Interacts with HABP4, KRT1 and OTUB1. Interacts with SRC (via SH2 domain); the interaction is enhanced by tyrosine phosphorylation of GNB2L1/RACK1. Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and PRKCA. Interacts with AR. Interacts with IGF1R but not with INSR. Interacts with ADAM12. Interacts with CLEC1B (via N-terminal region) and with HIF1A; the interaction promotes their degradation. Interacts with RHOA; this enhances RHOA activation and promotes cell migration. Interacts with CHRM2; the interaction regulates CHRM2 internalization. Interacts with TRPM6 (via kinase domain). Interacts with PTK2/FAK1; required for PTK2/FAK1 phosphorylation and dephosphorylation. Interacts with FLT1. Interacts with TBXA2R isoform 2. Interacts with HRAS. Interacts with Y.pseudotuberculosis yopK. Interacts with a number of viral proteins including Epstein-Barr virus BZLF1 and HIV-1 Nef; interaction with Nef increases Nef phosphorylation by PKC.
• Subcellular location: Cell membrane; Peripheral membrane protein. Cytoplasm. Cytoplasm › perinuclear region. Cytoplasm › cytoskeleton. Nucleus. Perikaryon . Cell projection › dendrite . Cell projection › phagocytic cup. Note: Recruited to the plasma membrane through interaction with KRT1 which binds to membrane-bound ITGB1. Also associated with the membrane in oncogene-transformed cells. PKC activation induces translocation from the perinuclear region to the cell periphery. In the brain, detected mainly in cell bodies and dendrites with little expression in axonal fibers or nuclei. Localized to phagocytic cups following infection by Y.pestis.
• Tissue specificity: In the liver, expressed at higher levels in activated hepatic stellate cells than in hepatocytes or Kupffer cells. Up-regulated in hepatocellular carcinomas and in the adjacent non-tumor liver tissue.
• Sequence caution: The sequence AAO21313.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
  The sequence AAR24619.1 differs from that shown. Reason: Frameshift at position 94.

General information above from UniProt

Function for RACK1 (GNB2L1) Protein

UniProtKB:

RACK1 is involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. RACK1 interacts with a wide variety of proteins and plays a role in many cellular processes. RACK1 is component of the 40S ribosomal subunit involved in translational repression. RACK1 binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. RACK1 may recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. RACK1 inhibits the activity of SRC kinases including SRC, LCK and YES1. RACK1 inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. RACK1 enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. RACK1 facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. RACK1 modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. RACK1 is involved in PKC-dependent translocation of ADAM12 to the cell membrane. RACK1 promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. RACK1 is required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. RACK1 is required for PTK2/FAK1 phosphorylation and dephosphorylation. RACK1 regulates internalization of the muscarinic receptor CHRM2. RACK1 promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. RACK1 inhibits TRPM6 channel activity. RACK1 regulates cell surface expression of some GPCRs such as TBXA2R. RACK1 plays a role in regulation of FLT1-mediated cell migration. RACK1 binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. RACK1 enhances phosphorylation of HIV-1 Nef by PKCs. RACK1 promotes migration of breast carcinoma cells by binding to and activating RHOA.

Genatlas:

• RACK1 plays a central role in early signaling through the Jak-STAT pathway
• RACK1 is a IGF-IR signaling molecule that functions as a positive mediator of cell spreading and contact with extracellular matrix
• RACK1 serves as a scaffold protein for a multiprotein complex that includes the IFN-alpha receptor 2/beta-chain of the receptor, STAT1, Janus kinase 1, tyrosine kinase 2, IL-2, IL-4, and erythropoietin
• RACK1 is involved in membrane anchorage of protein kinase C
• RACK1 is an important SRC substrate that signals downstream of growth factor receptor tyrosine kinases and is involved in the regulation of SRC function and cell growth
• RACK1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex
• RACK1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin
• RACK1 plays an an important role during CNS development and having multiple functions in the adult brain
• RACK1 is involved in mediating the PKC-dependent translocation of ADAM12 to membranes of activated hepatic stellate cells
• RACK1 roles in protecting cancer cells from apoptosis by regulating the degradation of GNB2L1, which together with CISH could play an important role of drug resistance in chemotherapy
• RACK1 activates SLC9A5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion
• RACK1 functions from the ribosome, implying a physical link between the eukaryotic ribosome and cell signaling pathways
• RACK1 has a dual role as both a signaling scaffold and a ribosomal protein
• RACK1 induces apoptosis of the cells, partly by inhibiting SRC
• RACK1 induces apoptosis by blocking SRC activation of the AKT cell survival pathway
• Partly by inhibiting SRC, RACK1 promotes mitochondrial cell death and blocks AKT-mediated cell survival
• RACK1 is component of the mammalian circadian clock
• RACK1 alters the conformation of particulate-associated PDE4D5 and mediates PKC-dependent activation of PDE4D5 in the particulate fraction of HEK-293 cells in response to elevations in intracellular cAMP
• RACK1 may play a role in PKC/PPP1R14A signaling pathway
• RACK1 has a dominant-negative effect on VANGL2 localization and gastrulation
• RACK1 regulates the localization of an essential planar cell polarity (PCP) protein and acts as a molecular switch to promote PCP signaling
• plays a crucial regulatory role in promoting PI3K/AKT1-RAC1 activation
• RACK1 is implicated in a novel signaling cascade that translocates DSH (Dishevelled) to the plasma membrane and regulates vertebrate neural tube closure
• RACK1 is a novel function in maintaining the junctional homeostasis of intestinal epithelial cells by regulation of the SRC- and growth factor-induced endocytosis of CDH1

Homology for human RACK1 (GNB2L1)

• ortholog to Gnb2l1, Mus musculus
• ortholog to Gnb2l1, Rattus norvegicus
• ortholog to gnb2l1, Danio rerio
• homolog to beta subunit implicated in membrane anchorage of the beta adrenergic receptor