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    GRK4 G protein-coupled receptor kinase 4 [ Homo sapiens (human) ]

    Gene ID: 2868, updated on 18-Sep-2018

    Summary

    Official Symbol
    GRK4provided by HGNC
    Official Full Name
    G protein-coupled receptor kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:4543
    See related
    Ensembl:ENSG00000125388 MIM:137026; Vega:OTTHUMG00000159914
    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
    IT11; GPRK4; GRK4a; GPRK2L
    Summary
    This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
    Expression
    Biased expression in testis (RPKM 14.6) and brain (RPKM 0.7) See more
    Orthologs

    Genomic context

    See GRK4 in Genome Data Viewer
    Location:
    4p16.3
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 4 NC_000004.12 (2963504..3040760)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (2965232..3042474)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene NOP14 antisense RNA 1 Neighboring gene major facilitator superfamily domain containing 10 Neighboring gene NOP14 nucleolar protein Neighboring gene RNA, U6 small nuclear 204, pseudogene Neighboring gene HTT antisense RNA

    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?

    Pathways from BioSystems

    • Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
      Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
    • 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...
    • 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...
    • Inactivation, recovery and regulation of the phototransduction cascade, organism-specific biosystem (from REACTOME)
      Inactivation, recovery and regulation of the phototransduction cascade, organism-specific biosystemTo terminate the single photon response and restore the system to its basal state, the three activated intermediates in phototransduction, rhodopsin (MII), transducin alpha subunit with GTP bound (GN...
    • 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 ...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • 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...
    • The phototransduction cascade, organism-specific biosystem (from REACTOME)
      The phototransduction cascade, organism-specific biosystemThe visual pigment (rhodopsin in rods) consists of an 11-cis-retinal (11cRAL) chromophore covalently attached to a GPCR opsin family member via a Schiff base linkage. Upon photon absorption, 11cRAL i...
    • Visual phototransduction, organism-specific biosystem (from REACTOME)
      Visual phototransduction, organism-specific biosystemVisual phototransduction is the process by which photon absorption by visual pigment molecules in photoreceptor cells is converted to an electrical cellular response. The events in this process are p...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    G protein-coupled receptor kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    rhodopsin kinase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    G protein-coupled receptor internalization IEA
    Inferred from Electronic Annotation
    more info
     
    protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    receptor internalization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of rhodopsin mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cell cortex IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol IEA
    Inferred from Electronic Annotation
    more info
     
    dendrite IEA
    Inferred from Electronic Annotation
    more info
     
    neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
     
    photoreceptor disc membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    G protein-coupled receptor kinase 4
    Names
    G protein-coupled receptor kinase 2-like
    NP_001004056.1
    NP_001004057.1
    NP_001337102.1
    NP_005298.2
    NP_892027.2
    XP_005248019.1
    XP_006713943.1
    XP_011511749.1
    XP_011511750.1
    XP_011511751.1
    XP_011511752.1
    XP_011511753.1
    XP_011511754.1
    XP_011511755.1
    XP_011511756.1
    XP_011511757.1
    XP_011511758.1
    XP_011511759.1
    XP_016863541.1
    XP_016863542.1
    XP_016863543.1
    XP_016863544.1
    XP_016863545.1
    XP_016863546.1
    XP_016863547.1
    XP_016863548.1
    XP_016863551.1
    XP_016863552.1
    XP_016863553.1
    XP_016863554.1
    XP_016863555.1
    XP_024309783.1

    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.

    Genomic

    1. NG_029102.1 RefSeqGene

      Range
      5001..82132
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001004056.1NP_001004056.1  G protein-coupled receptor kinase 4 isoform beta

      See identical proteins and their annotated locations for NP_001004056.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (beta) has the same N- and C-termini but is shorter compared to isoform alpha.
      Source sequence(s)
      BC027597, BI465220, BM725978, U33054, X97881
      Consensus CDS
      CCDS47002.1
      UniProtKB/Swiss-Prot
      P32298
      Related
      ENSP00000264764.8, OTTHUMP00000216995, ENST00000345167.10, OTTHUMT00000358180
      Conserved Domains (3) summary
      cd05631
      Location:154438
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:155417
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:20152
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    2. NM_001004057.1NP_001004057.1  G protein-coupled receptor kinase 4 isoform gamma

      See identical proteins and their annotated locations for NP_001004057.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (gamma) has the same N- and C-termini but is shorter compared to isoform alpha.
      Source sequence(s)
      BC027597, BI465220, BM725978, X97880
      Consensus CDS
      CCDS33947.1
      UniProtKB/Swiss-Prot
      P32298
      Related
      ENSP00000427445.1, OTTHUMP00000221010, ENST00000504933.1, OTTHUMT00000366764
      Conserved Domains (3) summary
      cd05631
      Location:186470
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:187449
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    3. NM_001350173.1NP_001337102.1  G protein-coupled receptor kinase 4 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 5, which has a shorter and distinct N-terminus, compared to isoform alpha.
      Source sequence(s)
      AK223581, AK292390, BI792406, N23898, X97881
      Conserved Domains (1) summary
      cl21453
      Location:5276
      PKc_like; Protein Kinases, catalytic domain
    4. NM_005307.2NP_005298.2  G protein-coupled receptor kinase 4 isoform delta

      See identical proteins and their annotated locations for NP_005298.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (delta) has the same N- and C-termini but is shorter compared to isoform alpha.
      Source sequence(s)
      AK223581, X97879
      Consensus CDS
      CCDS68656.1
      UniProtKB/Swiss-Prot
      P32298
      Related
      ENSP00000381128.4, OTTHUMP00000216993, ENST00000398051.8, OTTHUMT00000358177
      Conserved Domains (3) summary
      cd05631
      Location:154438
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:155417
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:20152
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    5. NM_182982.2NP_892027.2  G protein-coupled receptor kinase 4 isoform alpha

      See identical proteins and their annotated locations for NP_892027.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (alpha).
      Source sequence(s)
      BC027597, BI465220, BM725978, U33054, X97881
      Consensus CDS
      CCDS33946.1
      UniProtKB/Swiss-Prot
      P32298
      Related
      ENSP00000381129.4, OTTHUMP00000216992, ENST00000398052.8, OTTHUMT00000358176
      Conserved Domains (3) summary
      cd05631
      Location:186470
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:187449
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily

    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_000004.12 Reference GRCh38.p12 Primary Assembly

      Range
      2963504..3040760
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011513447.2XP_011511749.1  G protein-coupled receptor kinase 4 isoform X1

      Conserved Domains (3) summary
      cd05631
      Location:186509
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:187488
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    2. XM_017008053.1XP_016863542.1  G protein-coupled receptor kinase 4 isoform X4

    3. XM_017008052.1XP_016863541.1  G protein-coupled receptor kinase 4 isoform X3

    4. XM_011513449.2XP_011511751.1  G protein-coupled receptor kinase 4 isoform X5

      Conserved Domains (3) summary
      cd05631
      Location:154477
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:155456
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:20152
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    5. XM_011513450.2XP_011511752.1  G protein-coupled receptor kinase 4 isoform X6

      Conserved Domains (3) summary
      cd05631
      Location:186509
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      smart00220
      Location:187488
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
    6. XM_011513453.2XP_011511755.1  G protein-coupled receptor kinase 4 isoform X9

      Conserved Domains (3) summary
      smart00220
      Location:187488
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186508
      PKc_like; Protein Kinases, catalytic domain
    7. XM_011513451.2XP_011511753.1  G protein-coupled receptor kinase 4 isoform X7

      Conserved Domains (3) summary
      smart00220
      Location:187462
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186470
      PKc_like; Protein Kinases, catalytic domain
    8. XM_011513454.2XP_011511756.1  G protein-coupled receptor kinase 4 isoform X10

      Conserved Domains (3) summary
      smart00220
      Location:187462
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186470
      PKc_like; Protein Kinases, catalytic domain
    9. XM_011513455.2XP_011511757.1  G protein-coupled receptor kinase 4 isoform X12

      Conserved Domains (3) summary
      smart00220
      Location:187471
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186472
      PKc_like; Protein Kinases, catalytic domain
    10. XM_011513456.2XP_011511758.1  G protein-coupled receptor kinase 4 isoform X15

      Conserved Domains (2) summary
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186363
      PKc_like; Protein Kinases, catalytic domain
    11. XM_017008065.1XP_016863554.1  G protein-coupled receptor kinase 4 isoform X21

    12. XM_017008054.1XP_016863543.1  G protein-coupled receptor kinase 4 isoform X11

    13. XM_017008056.1XP_016863545.1  G protein-coupled receptor kinase 4 isoform X14

    14. XM_017008055.1XP_016863544.1  G protein-coupled receptor kinase 4 isoform X13

    15. XM_011513452.2XP_011511754.1  G protein-coupled receptor kinase 4 isoform X8

      Conserved Domains (3) summary
      cd08750
      Location:52184
      RGS_GRK4; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4)
      smart00220
      Location:187462
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:186470
      PKc_like; Protein Kinases, catalytic domain
    16. XM_011513448.2XP_011511750.1  G protein-coupled receptor kinase 4 isoform X2

      Conserved Domains (3) summary
      cd05631
      Location:186509
      STKc_GRK4; Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
      cd08750
      Location:52184
      RGS_GRK4; Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4)
      smart00220
      Location:187488
      S_TKc; Serine/Threonine protein kinases, catalytic domain
    17. XM_011513457.2XP_011511759.1  G protein-coupled receptor kinase 4 isoform X20

      Conserved Domains (2) summary
      cl02565
      Location:52184
      RGS; Regulator of G protein signaling (RGS) domain superfamily
      cl21453
      Location:186286
      PKc_like; Protein Kinases, catalytic domain
    18. XM_017008062.1XP_016863551.1  G protein-coupled receptor kinase 4 isoform X17

      Conserved Domains (2) summary
      smart00220
      Location:20238
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:1259
      PKc_like; Protein Kinases, catalytic domain
    19. XM_017008059.2XP_016863548.1  G protein-coupled receptor kinase 4 isoform X16

      Conserved Domains (1) summary
      cl21453
      Location:5276
      PKc_like; Protein Kinases, catalytic domain
    20. XM_005247962.3XP_005248019.1  G protein-coupled receptor kinase 4 isoform X17

      See identical proteins and their annotated locations for XP_005248019.1

      Conserved Domains (2) summary
      smart00220
      Location:20238
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:1259
      PKc_like; Protein Kinases, catalytic domain
    21. XM_017008064.1XP_016863553.1  G protein-coupled receptor kinase 4 isoform X19

    22. XM_017008058.1XP_016863547.1  G protein-coupled receptor kinase 4 isoform X16

      Conserved Domains (1) summary
      cl21453
      Location:5276
      PKc_like; Protein Kinases, catalytic domain
    23. XM_006713880.3XP_006713943.1  G protein-coupled receptor kinase 4 isoform X17

      See identical proteins and their annotated locations for XP_006713943.1

      Conserved Domains (2) summary
      smart00220
      Location:20238
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:1259
      PKc_like; Protein Kinases, catalytic domain
    24. XM_017008066.1XP_016863555.1  G protein-coupled receptor kinase 4 isoform X22

    25. XM_024454015.1XP_024309783.1  G protein-coupled receptor kinase 4 isoform X16

      Conserved Domains (1) summary
      cl21453
      Location:5276
      PKc_like; Protein Kinases, catalytic domain
    26. XM_017008057.1XP_016863546.1  G protein-coupled receptor kinase 4 isoform X16

      Conserved Domains (1) summary
      cl21453
      Location:5276
      PKc_like; Protein Kinases, catalytic domain
    27. XM_017008063.1XP_016863552.1  G protein-coupled receptor kinase 4 isoform X18

    RNA

    1. XR_001741211.1 RNA Sequence

    2. XR_924943.2 RNA Sequence

    3. XR_924941.2 RNA Sequence

    4. XR_001741210.1 RNA Sequence

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