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    GRK2 G protein-coupled receptor kinase 2 [ Homo sapiens (human) ]

    Gene ID: 156, updated on 7-Oct-2018

    Summary

    Official Symbol
    GRK2provided by HGNC
    Official Full Name
    G protein-coupled receptor kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:289
    See related
    Ensembl:ENSG00000173020 MIM:109635; Vega:OTTHUMG00000167104
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BARK1; ADRBK1; BETA-ARK1
    Summary
    This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer's disease. [provided by RefSeq, Sep 2017]
    Expression
    Broad expression in bone marrow (RPKM 91.8), spleen (RPKM 61.9) and 24 other tissues See more
    Orthologs

    Genomic context

    See GRK2 in Genome Data Viewer
    Location:
    11q13.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (67266400..67286558)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (67033905..67054029)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene translation initiation factor IF-2-like Neighboring gene lysine demethylase 2A Neighboring gene ankyrin repeat domain 13D Neighboring gene slingshot protein phosphatase 3

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of adrenergic, beta, receptor kinase 1 (ADRBK1) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed
    Knockdown of adrenergic, beta, receptor kinase 1 (ADRBK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • Activation of SMO, organism-specific biosystem (from REACTOME)
      Activation of SMO, organism-specific biosystemActivation of the transmembrane protein SMO in response to Hh stimulation is a major control point in the Hh signaling pathway (reviewed in Ayers and Therond, 2010; Jiang and Hui, 2008). In the absen...
    • CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      CXCR4-mediated signaling events, organism-specific biosystem
      CXCR4-mediated signaling events
    • Ca-dependent events, organism-specific biosystem (from REACTOME)
      Ca-dependent events, organism-specific biosystemCalcium, as the ion Ca2+, is essential in many biological processes. The majority of Ca2+ in many organisms is bound to phosphates which form skeletal structures and also buffer Ca2+ levels in extrac...
    • CaM pathway, organism-specific biosystem (from REACTOME)
      CaM pathway, organism-specific biosystemCalmodulin (CaM) is a small acidic protein that contains four EF-hand motifs, each of which can bind a calcium ion, therefore it can bind up to four calcium ions. The protein has two approximately sy...
    • Calmodulin induced events, organism-specific biosystem (from REACTOME)
      Calmodulin induced events, organism-specific biosystemOne important physiological role for Calmodulin is the regulation of adenylylcyclases. Four of the nine known adenylylcyclases are calcium sensitive, in particular type 8 (AC8).
    • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
      Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
    • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
      Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Chemokine signaling pathway, conserved biosystem (from KEGG)
      Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
      Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
    • DAG and IP3 signaling, organism-specific biosystem (from REACTOME)
      DAG and IP3 signaling, organism-specific biosystemThis pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.
    • DAP12 interactions, organism-specific biosystem (from REACTOME)
      DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
    • DAP12 signaling, organism-specific biosystem (from REACTOME)
      DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • EGFR interacts with phospholipase C-gamma, organism-specific biosystem (from REACTOME)
      EGFR interacts with phospholipase C-gamma, organism-specific biosystemActivated epidermal growth factor receptors (EGFR) can stimulate phosphatidylinositol (PI) turnover. Activated EGFR can activate phospholipase C-gamma1 (PLC-gamma1, i.e. PLCG1) which hydrolyses phosp...
    • Endocytosis, organism-specific biosystem (from KEGG)
      Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
    • Endocytosis, conserved biosystem (from KEGG)
      Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
    • G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
    • G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
    • G-protein mediated events, organism-specific biosystem (from REACTOME)
      G-protein mediated events, organism-specific biosystemWhen dissociated Galpha-GTP and Gbeta-gamma can activate or inhibit different signalling cascades and effector proteins. The precise pathways depends on the identity of the alpha and beta/gamma subty...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
      Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
    • Glutamatergic synapse, organism-specific biosystem (from KEGG)
      Glutamatergic synapse, organism-specific biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Glutamatergic synapse, conserved biosystem (from KEGG)
      Glutamatergic synapse, conserved biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Hedgehog 'on' state, organism-specific biosystem (from REACTOME)
      Hedgehog 'on' state, organism-specific biosystemHedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh ...
    • Hedgehog Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Hedgehog Signaling Pathway, organism-specific biosystemThe Hedgehog family of proteins are signaling proteins that are crucial for a number of physiological processes including morphogenesis during development. In adult organisms, it is also involved in ...
    • Hedgehog signaling pathway, organism-specific biosystem (from KEGG)
      Hedgehog signaling pathway, organism-specific biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
    • Hedgehog signaling pathway, conserved biosystem (from KEGG)
      Hedgehog signaling pathway, conserved biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Membrane Trafficking, organism-specific biosystem (from REACTOME)
      Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
    • Morphine addiction, organism-specific biosystem (from KEGG)
      Morphine addiction, organism-specific biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • Morphine addiction, conserved biosystem (from KEGG)
      Morphine addiction, conserved biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Olfactory transduction, organism-specific biosystem (from KEGG)
      Olfactory transduction, organism-specific biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
    • Olfactory transduction, conserved biosystem (from KEGG)
      Olfactory transduction, conserved biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
    • Opioid Signalling, organism-specific biosystem (from REACTOME)
      Opioid Signalling, organism-specific biosystemOpioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as...
    • PLC beta mediated events, organism-specific biosystem (from REACTOME)
      PLC beta mediated events, organism-specific biosystemThe phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. PLC hydrolyzes phosphatidylinosito...
    • PLC-gamma1 signalling, organism-specific biosystem (from REACTOME)
      PLC-gamma1 signalling, organism-specific biosystemThe activation of phosphlipase C-gamma (PLC-gamma) and subsequent mobilization of calcium from intracellular stores are essential for neurotrophin secretion. PLC-gamma is activated through the phosph...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Signaling by Hedgehog, organism-specific biosystem (from REACTOME)
      Signaling by Hedgehog, organism-specific biosystemHedgehog (Hh) is a secreted morphogen that regulates developmental processes in vertebrates including limb bud formation, neural tube patterning, cell growth and differentiation (reviewed in Hui and ...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling events mediated by HDAC Class II, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by HDAC Class II, organism-specific biosystem
      Signaling events mediated by HDAC Class II
    • Signaling events mediated by the Hedgehog family, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by the Hedgehog family, organism-specific biosystem
      Signaling events mediated by the Hedgehog family
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Thromboxane A2 receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
      Thromboxane A2 receptor signaling, organism-specific biosystem
      Thromboxane A2 receptor signaling
    • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
      Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • FLJ16718

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    Edg-2 lysophosphatidic acid receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    G protein-coupled receptor kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    alpha-2A adrenergic receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    beta-adrenergic receptor kinase activity TAS
    Traceable Author Statement
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    G protein-coupled acetylcholine receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    desensitization of G protein-coupled receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    heart development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of striated muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of the force of heart contraction by chemical signal IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    peptidyl-serine phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    peptidyl-threonine phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of catecholamine secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    receptor internalization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    tachykinin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    viral entry into host cell IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    cilium TAS
    Traceable Author Statement
    more info
     
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    membrane HDA PubMed 
    membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    beta-adrenergic receptor kinase 1
    Names
    adrenergic beta receptor kinase 1
    beta-ARK-1
    NP_001610.2
    XP_011543075.1
    XP_024304144.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001619.4NP_001610.2  beta-adrenergic receptor kinase 1

      See identical proteins and their annotated locations for NP_001610.2

      Status: REVIEWED

      Source sequence(s)
      AI888604, BC090863, DN989901
      Consensus CDS
      CCDS8156.1
      UniProtKB/Swiss-Prot
      P25098
      UniProtKB/TrEMBL
      A0A0S2Z392
      Related
      ENSP00000312262.5, OTTHUMP00000235171, ENST00000308595.9
      Conserved Domains (3) summary
      cd08747
      Location:30186
      RGS_GRK2_GRK3; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3)
      cd01240
      Location:553670
      PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain
      cd14223
      Location:190510
      STKc_GRK2; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

      Range
      67266400..67286558
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011544773.1XP_011543075.1  beta-adrenergic receptor kinase 1 isoform X2

      See identical proteins and their annotated locations for XP_011543075.1

      Conserved Domains (5) summary
      cd08747
      Location:8156
      RGS_GRK2_GRK3; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3)
      cd01240
      Location:523640
      PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain
      cd14223
      Location:160480
      STKc_GRK2; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2
      pfam00069
      Location:161423
      Pkinase; Protein kinase domain
      pfam00169
      Location:530620
      PH; PH domain
    2. XM_024448376.1XP_024304144.1  beta-adrenergic receptor kinase 1 isoform X1

      Conserved Domains (3) summary
      cd08747
      Location:13161
      RGS_GRK2_GRK3; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3)
      cd01240
      Location:528645
      PH_GRK2_subgroup; G Protein-Coupled Receptor Kinase 2 subgroup pleckstrin homology (PH) domain
      cd14223
      Location:165485
      STKc_GRK2; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2

    RNA

    1. XR_001747779.1 RNA Sequence

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