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FLASH GENE
Symbol GNB2L1 contributors: mct/shn - updated : 17-05-2012
HGNC name guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1
HGNC id 4399
Location 5q35.3      Physical location : 180.663.927 - 180.670.906
Synonym name
  • 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
  • Synonym symbol(s) RACK1, H12.3, GNB2, RS1, GBLP, Gnb2-rs1, PIG21, Gnb2-rs1 HLC7, HLC-7
    DNA
    TYPE functioning gene
    STRUCTURE 6.98 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • DHEA mediated GNB2L1 regulation is modulated by distant elements (enhancer/silencer)
  • LPS, PMA and cortisol can act directly on the promoter
  • the imbalance between DHEA and cortisol during aging could be important in recoery of the RACK1 expression (Del Vecchio 2009)
  • MAPPING cloned Y linked N status inconsistent : contradictory evidence
    Map cen - D5S408 - D5S2006 - GNB2L1 - qter
    Physical map
    LOC391860 5 similar to 40S ribosomal protein S8 MAPK9 5q35 mitogen-activated protein kinase 9 GFPT2 5q34-q35 glutamine-fructose-6-phosphate transaminase 2 KIAA1194 5q35.3 Homo sapiens KIAA1194 (KIAA1194), mRNA. SCGB3A1 5q35-qter secretoglobin, family 3A, member 1 FLT4 5q35.3 fms-related tyrosine kinase 4 LOC134082 5q35.3 similar to seven transmembrane helix receptor LOC134083 5q35.3 similar to Olfactory receptor 2Y1 MGAT1 5q35 mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase FLJ21458 5q35.3 hypothetical protein FLJ21458 LOC391861 5 similar to cAMP-regulated phosphoprotein 19 (ARPP-19) BTNL3 5q35 butyrophilin-like 3 FLJ32535 5q35.3 butyrophilin 3 FOXO1B 5q35.2-q35.3 forkhead box O1B LOC340050 5q35.3 similar to hypothetical protein LOC340052 5q35.3 similar to seven transmembrane helix receptor LOC285659 5q35.3 similar to Olfactory receptor 2V3 LOC389353 5 LOC389353 TRIM7 5q35.3 tripartite motif-containing 7 TRIM41 5q35.3 tripartite motif-containing 41 GNB2L1 5q35.3-qter guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1 FLJ23053 5q35.3 hypothetical protein FLJ23053 TRIM52 5q35.3 tripartite motif-containing 52 LOC389354 5 hypothetical gene supported by AL137733 LOC389355 5 similar to bA476I15.3 (novel protein similar to septin) LOC391862 5 similar to Olfactory receptor 4F3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1125 35.1 317 - 2007 17900862
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
     tonsils   highly
    Nervousbrain   highly
    Reproductivefemale systembreastmammary gland  
    Skin/Tegumentskin   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal alpha-helical segment
  • seven WD (Trp-Asp) repeats, forming a propeller structure (WD5 directly binds NHERF1 through its PDZ1 domain)
  • a pleckstrin homology (PH) domains
  • two short sequences homolog to a PKC binding sequence of annexin 1
  • a VANGL2-interacting domain having a dominant-negative effect on membrane targeting of VANGL2, parallel to its dominant-negative effect on gastrulation
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to Gnb2l1, Mus musculus
    ortholog to Gnb2l1, Rattus norvegicus
    ortholog to gnb2l1, Danio rerio
    intraspecies homolog to beta subunit implicated in membrane anchorage of the beta adrenergic receptor
    Homologene
    FAMILY
  • WD repeat G protein beta family
  • CATEGORY signaling , receptor membrane G
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,ribosome
    intracellular,nucleus
    text although not required for all GNB2L1 activities, localization at ribosomes is integral to some aspects of GNB2L1 function
    basic FUNCTION
  • plays a central role in early signaling through the Jak-STAT pathway
  • is a IGF-IR signaling molecule that functions as a positive mediator of cell spreading and contact with extracellular matrix
  • 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
  • involved in membrane anchorage of protein kinase C
  • important SRC substrate that signals downstream of growth factor receptor tyrosine kinases and is involved in the regulation of SRC function and cell growth
  • functioning as an adaptor recruiting the transcription factor STAT1 to the receptor complex
  • may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin
  • playing an an important role during CNS development and having multiple functions in the adult brain
  • involved in mediating the PKC-dependent translocation of ADAM12 to membranes of activated hepatic stellate cells
  • role 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
  • activates SLC9A5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion
  • functions from the ribosome, implying a physical link between the eukaryotic ribosome and cell signaling pathways
  • having a dual role as both a signaling scaffold and a ribosomal protein
  • induces apoptosis of the cells, partly by inhibiting SRC
  • induces apoptosis by blocking SRC activation of the AKT cell survival pathway
  • partly by inhibiting SRC, promotes mitochondrial cell death and blocks AKT-mediated cell survival
  • component of the mammalian circadian clock
  • 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
  • may play a role in PKC/PPP1R14A signaling pathway
  • has a dominant-negative effect on VANGL2 localization and gastrulation
  • 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
  • implicated in a novel signaling cascade that translocates DSH (Dishevelled) to the plasma membrane and regulates vertebrate neural tube closure
  • a novel function in maintaining the junctional homeostasis of intestinal epithelial cells by regulation of the SRC- and growth factor-induced endocytosis of CDH1
  • important positive regulator of SHH/GLI-dependent signaling in non-small-cell lung cancer (NSCLC)
  • is a ribosomal scaffold protein for specific mRNA-RBP complexes to tightly regulate the translation of specific mRNAs
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • core component of the eukaryotic 40S ribosomal subunit
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Phospholipase C-gamma 1, PLC-gamma 1
  • integrin beta subunit
  • cAMP-specific phosphodiesterase PDE4D5
  • PLCgamma, beta-chain of the IL-5/IL-3/GM-CSF receptor and Src kinases
  • A73
  • ADAM12 interacting protein, thereby modulating the PKC-dependent translocation of ADAM12 to the membrane
  • GRB2-related adapter protein 2, GRID
  • Epstein-Barr virus activator protein BZLF1
  • I IFN receptor chain 2, IFNAR2c
  • protein tyrosine phosphatase mu, PTPmu
  • HIV-1 Nef
  • PH domain of p120GAP
  • Angiotensin II Receptor-Associated Protein, AGTRAP
  • IGF-IR, protein kinase C, and beta1 integrin in response to IGF-I and phorbol 12-myristate 13-acetate stimulation
  • NR2B subunit of the NMDA receptor and the nonreceptor protein-tyrosine kinase, Fyn
  • betagamma subunit of heterotrimeric G proteins
  • Factor associated with neutral sphingomyelinase activation, FAN
  • PKCalpha and beta1 integrin
  • uclear factor of activated T cells, NFAT
  • p73alpha
  • suppression of tumorigenicity 7, ST7
  • beta-tubulin
  • androgen receptor, AR
  • eukaryotic translation initiation factor 6, EIF6
  • Ki-1/57
  • dopamine transporter, DAT
  • signal transducer and activator of transcription 3, STAT3
  • directly binds to SLC9A5 and positively regulates the transporter function (regulates SLC9A5 both directly and through an integrin-dependent pathway)
  • Spermidine/spermine N(1)-acetyltransferase-1
  • dynein light chain 1
  • OTU domain, ubiquitin aldehyde binding 1, OTUB1
  • associating with the cytoplasmic tail of CLEC1B and promoting its ubiquitin-proteasome degradation
  • brain and muscle ARNT-like 1, BMAL1
  • binds to FLT1, and regulates FLT1-mediated cell migration via activation of a PI3K/Akt pathway
  • interacting protein of a vertebrate Vang protein, VANGL2
  • essential component for VANGL2 membrane targeting and an additional molecular component required for PCP signaling while modulating canonical Wnt signaling
  • binds to FLT1
  • a novel interaction partner of PTK7, a regulator of planar cell polarity that is necessary for neural tube closure
  • required to promote the transcription of the brain-derived neurotrophic factor (BDNF)
  • YWHAZ is a direct binding partner of GNB2L1 7)
  • WDR26 also controlled GNB2L1, a negative regulator, in binding GNG2/GNB1 and inhibiting leukocyte migration
  • nuclear GNB2L1 is required to promote the transcription of the brain-derived neurotrophic factor (BDNF) 7)
  • interacts with the receptor for activated-C kinase 1 (GNB2L1), a scaffold protein that folds into a seven-blade propeller
  • binds the Ras-interacting domain of the RALGDS family of proteins, which are essential effectors of activated RAS
  • binds the Beta-actin mRNA/ZBP1 complex on ribosomes and contributes to the release of beta-actin mRNA from ZBP1 and to its translation
  • novel role of GNB2L1, physically interacting with PCBP1 and participating in the regulation of OPRM1 gene expression in neuronal NMB cells
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in the endothelium of tumor neovascularization
    tumoral     --over  
    in patients with hepatocellular carcinoma
    tumoral     --over  
    in Non-small-cell lung cancer (NSCLC) samples, and its expression correlated with tumor stage, metastasis, and degree of differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • serves as a potential biomarker of Non-small-cell lung cancer (NSCLC)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    serves as a therapeutic target of NSCLC
    cancerdigestivecolon
    inhibits growth and induces death of colon cells, suggesting novel colon cancer therapies that mimic GNB2L1 function
    ANIMAL & CELL MODELS
  • RACK1 overexpression resulted in reduced IGF-I-induced cell growth in both anchorage-dependent, anchorage-independent conditions enhanced cell spreading, increased stress fibers, increased focal adhesions accompanied by increased tyrosine phosphorylation of focal adhesion kinase and paxillin