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RACK1

Domain

The 7 WD repeats mediate protein-protein interactions with binding partners.

Function

Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158).

(Microbial infection) Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells.

(Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs.

(Microbial infection) In case of poxvirus infection, remodels the ribosomes so that they become optimal for the viral mRNAs (containing poly-A leaders) translation but not for host mRNAs.

(Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses.

Post-translational modifications

Phosphorylated on Tyr-228 and/or Tyr-246 by SRC. This is required for binding to SRC.

(Microbial infection) Phosphorylated by vaccinia virus B1 kinase on serine and threonine residues; this phosphorylation remodels the ribosome properties, favoring the viral mRNA translation.

Sequence similarities

Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.

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.

Cellular localization

  • Cell membrane
  • Peripheral membrane protein
  • Cytoplasm
  • Cytoplasm
  • Perinuclear region
  • Nucleus
  • Perikaryon
  • Cell projection
  • Dendrite
  • Cell projection
  • Phagocytic cup
  • Recruited to the plasma membrane through interaction with KRT1 which binds to membrane-bound ITGB1 (PubMed:17956333). Also associated with the membrane in oncogene-transformed cells (PubMed:11884618). PKC activation induces translocation from the perinuclear region to the cell periphery (PubMed:11279199). In the brain, detected mainly in cell bodies and dendrites with little expression in axonal fibers or nuclei (By similarity). Localized to phagocytic cups following infection by Y.pestis (PubMed:21347310).

Alternative names

  • Receptor of activated protein 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
  • Receptor for activated C kinase
  • Small ribosomal subunit protein RACK1
  • HLC-7
  • RACK1
  • PIG21
  • HLC7
  • GNB2L1

Target type

Proteins

Molecular weight

35077Da