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    PRKG2 protein kinase cGMP-dependent 2 [ Homo sapiens (human) ]

    Gene ID: 5593, updated on 11-Apr-2024

    Summary

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    Official Symbol
    PRKG2provided by HGNC
    Official Full Name
    protein kinase cGMP-dependent 2provided by HGNC
    Primary source
    HGNC:HGNC:9416
    See related
    Ensembl:ENSG00000138669 MIM:601591; AllianceGenome:HGNC:9416
    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
    AMD4; PKG2; SMDP; cGK2; cGKII; PRKGR2
    Summary
    This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein binds to and inhibits the activation of several receptor tyrosine kinases. The membrane-bound protein is a regulator of intestinal secretion, bone growth and renin secretion. Alternate splicing results in multiple transcript variants encoding distinct isoforms whose regulatory N-termini differ in length but whose C-terminal catalytic domains are identical. [provided by RefSeq, May 2018]
    Expression
    Biased expression in prostate (RPKM 4.2), small intestine (RPKM 4.1) and 11 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    4q21.21
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (81087370..81217836, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (84417063..84547534, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (82008524..82136376, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene cilia and flagella associated protein 299 Neighboring gene uncharacterized LOC105377305 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:81416935-81417840 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:81480892-81481084 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21656 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15523 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:82075133-82075646 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:82074618-82075132 Neighboring gene bone morphogenetic protein 3 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:82085265-82086464 Neighboring gene PRKG2 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:82135408-82135908 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:82135909-82136409 Neighboring gene uncharacterized LOC124900726 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:82296443-82296942 Neighboring gene RNA, U5A small nuclear 2, pseudogene Neighboring gene Sharpr-MPRA regulatory region 8336 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15524 Neighboring gene RasGEF domain family member 1B

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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 Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Natural history of clinical features in two brothers with acromesomelic dysplasia related to PRKG2. Mollaoğlu E, et al. Clin Genet, 2023 May. PMID 36504352
    2. Variable skeletal phenotypes associated with biallelic variants in PRKG2. Pagnamenta AT, et al. J Med Genet, 2022 Oct. PMID 34782440, Free PMC Article
    3. Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia. Díaz-González F, et al. J Med Genet, 2022 Jan. PMID 33106379
    4. Neutron Crystallography Detects Differences in Protein Dynamics: Structure of the PKG II Cyclic Nucleotide Binding Domain in Complex with an Activator. Gerlits O, et al. Biochemistry, 2018 Mar 27. PMID 29517905, Free PMC Article
    5. Protein Kinases Type II (PKG II) Combined with L-Arginine Significantly Ameliorated Xenograft Tumor Development: Is L-Arginine a Potential Alternative in PKG II Activation? Wu Y, et al. Med Sci Monit, 2018 Feb 5. PMID 29401205, Free PMC Article

    See all (63) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Natural history of clinical features in two brothers with acromesomelic dysplasia related to PRKG2.
      Title: Natural history of clinical features in two brothers with acromesomelic dysplasia related to PRKG2.
    2. Variable skeletal phenotypes associated with biallelic variants in PRKG2.
      Title: Variable skeletal phenotypes associated with biallelic variants in PRKG2.
    3. Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia.
      Title: Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia.
    4. Expression of PKG2 in ovarian cancer and its effect on epidermal growth factor receptor.
      Title: Expression of PKG2 in ovarian cancer and its effect on epidermal growth factor receptor.
    5. These findings suggested a PKG II-specific phosphorylation site on EGFR.
      Title: Type II cGMP-dependent protein kinase phosphorylates EGFR at threonine 669 and thereby inhibits its activation.
    6. L-Arginine is a potential alternative to PKG II activation.
      Title: Protein Kinases Type II (PKG II) Combined with L-Arginine Significantly Ameliorated Xenograft Tumor Development: Is L-Arginine a Potential Alternative in PKG II Activation?
    7. Comparative analysis of the backbone hydrogen/deuterium exchange patterns in PKG II:8-pCPT-cGMP and previously reported PKG Ibeta:cGMP XN structures suggests that the ability of these agonists to activate PKG is related to how effectively they quench dynamics of the cyclic nucleotide binding pocket and the surrounding regions.
      Title: Neutron Crystallography Detects Differences in Protein Dynamics: Structure of the PKG II Cyclic Nucleotide Binding Domain in Complex with an Activator.
    8. the results indicated that PKG II could block c-Met activation via phosphorylating Ser985
      Title: PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells.
    9. These affinity and activation measurements show that beta-phenyl-1,N2-ethenoguanosine 3',5'-monophosphate (PET-cGMP) is most selective for PKG I, whereas 8-(4-chlorophenylthio)guanosine-3'-5'-cyclic monophosphate (8-pCPT-cGMP) is most selective for PKG II.
      Title: Structural Basis of Analog Specificity in PKG I and II.
    10. PKG II inhibits EGFinduced activation of HER2 through binding with and causing threonine 686 phosphorylation of this oncogenic protein.
      Title: Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells.
    Submit: New GeneRIF Correction See all GeneRIFs (32)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Acromesomelic dysplasia 4
    MedGen: C5562028 OMIM: 619636 GeneReviews: Not available
    		not available
    Spondylometaphyseal dysplasia, pagnamenta type
    MedGen: C5562030 OMIM: 619638 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Gene-Smoking Interactions Identify Several Novel Blood Pressure Loci in the Framingham Heart Study.
    EBI GWAS Catalog
    Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
    EBI GWAS Catalog
    Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
    EBI GWAS Catalog
    Many sequence variants affecting diversity of adult human height.
    EBI GWAS Catalog
    Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cGMP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cGMP-dependent protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cGMP-dependent protein kinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables mitogen-activated protein kinase binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of chloride transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of chondrocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein localization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein kinase A signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in tetrahydrobiopterin metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    cGMP-dependent protein kinase 2
    Names
    cGMP-dependent protein kinase II
    protein kinase, cGMP-dependent, type II
    testicular tissue protein Li 99
    NP_001269409.1
    NP_001269410.1
    NP_001269411.1
    NP_001269412.1
    NP_001269414.1
    NP_001350330.1
    NP_006250.1
    XP_016863904.2
    XP_016863905.2
    XP_016863907.1
    XP_047271919.1
    XP_054206479.1
    XP_054206480.1
    XP_054206481.1

    NCBI Reference Sequences (RefSeq)

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    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_001282480.1 → NP_001269409.1  cGMP-dependent protein kinase 2 isoform b

      See identical proteins and their annotated locations for NP_001269409.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the use of an alternate promoter, and has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon compared to variant 1. The resulting isoform (b) has a shorter N-terminus compared to isoform a. Variants 2 and 3 encode the same protein.
      Source sequence(s)
      AC139722, AK297673, AK316140, BF508892, DA569289, X94612
      Consensus CDS
      CCDS75150.1
      UniProtKB/TrEMBL
      B4DLF9, B7ZA25
      Related
      ENSP00000439967.1, ENST00000545647.5
      Conserved Domains (1) summary
      cd05572
      Location:39 → 298
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    2. NM_001282481.1 → NP_001269410.1  cGMP-dependent protein kinase 2 isoform b

      See identical proteins and their annotated locations for NP_001269410.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the use of an alternate promoter, and has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon compared to variant 1. The resulting isoform (b) has a shorter N-terminus compared to isoform a. Variants 2 and 3 encode the same protein.
      Source sequence(s)
      AC139722, AK296979, AK297673, AK316140, BF508892, DA569289, X94612
      Consensus CDS
      CCDS75150.1
      UniProtKB/TrEMBL
      B4DLF9, B7ZA25
      Conserved Domains (1) summary
      cd05572
      Location:39 → 298
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    3. NM_001282482.1 → NP_001269411.1  cGMP-dependent protein kinase 2 isoform c

      See identical proteins and their annotated locations for NP_001269411.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the use of an alternate promoter, and has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a.
      Source sequence(s)
      AC139722, AK297673, AK316140, BF508892, DA569289, DC348270, X94612
      UniProtKB/TrEMBL
      B4DLF9
      Conserved Domains (1) summary
      cd05572
      Location:19 → 269
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    4. NM_001282483.1 → NP_001269412.1  cGMP-dependent protein kinase 2 isoform d

      See identical proteins and their annotated locations for NP_001269412.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) represents the use of an alternate promoter, and has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon compared to variant 1. The resulting isoform (d) has a shorter N-terminus compared to isoform a.
      Source sequence(s)
      AC139722, AK297673, AK316140, BF508892, DA462272, DA569289, X94612
      UniProtKB/TrEMBL
      B4DLF9
      Conserved Domains (1) summary
      cd05572
      Location:1 → 238
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    5. NM_001282485.2 → NP_001269414.1  cGMP-dependent protein kinase 2 isoform e

      See identical proteins and their annotated locations for NP_001269414.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate in-frame splice site in an internal exon compared to variant 1. The resulting isoform (e) is shorter compared to isoform a.
      Source sequence(s)
      AC098819, AC139722, AK297673, BF508892, DA569289, DB455792, X94612
      Consensus CDS
      CCDS64005.1
      UniProtKB/Swiss-Prot
      Q13237
      Related
      ENSP00000486129.1, ENST00000628926.1
      Conserved Domains (2) summary
      cd00038
      Location:286 → 401
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
      cd05572
      Location:439 → 689
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    6. NM_001363401.2 → NP_001350330.1  cGMP-dependent protein kinase 2 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses an alternate splice site in the 5' UTR, compared to variant 1, and encodes isoform a. Variants 1 and 7 encode the same isoform (a).
      Source sequence(s)
      AC098819, AC139722
      Consensus CDS
      CCDS3589.1
      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3
      Related
      ENSP00000378945.1, ENST00000395578.3
      Conserved Domains (2) summary
      cd00038
      Location:286 → 401
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
      cd05572
      Location:459 → 718
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    7. NM_006259.3 → NP_006250.1  cGMP-dependent protein kinase 2 isoform a

      See identical proteins and their annotated locations for NP_006250.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1 and 7 encode the same isoform (a).
      Source sequence(s)
      AC098819, AC139722, BF508892, DA569289, DB455792, X94612
      Consensus CDS
      CCDS3589.1
      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3
      Related
      ENSP00000264399.1, ENST00000264399.6
      Conserved Domains (2) summary
      cd00038
      Location:286 → 401
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
      cd05572
      Location:459 → 718
      STKc_cGK; Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      81087370..81217836 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017008415.2 → XP_016863904.2  cGMP-dependent protein kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3

    2. XM_017008416.2 → XP_016863905.2  cGMP-dependent protein kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3

    3. XM_047415963.1 → XP_047271919.1  cGMP-dependent protein kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3

    4. XM_017008418.1 → XP_016863907.1  cGMP-dependent protein kinase 2 isoform X2

      Conserved Domains (2) summary
      COG0664
      Location:162 → 285
      Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
      cd00038
      Location:286 → 401
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      84417063..84547534 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054350504.1 → XP_054206479.1  cGMP-dependent protein kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3

    2. XM_054350505.1 → XP_054206480.1  cGMP-dependent protein kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      B4DMX3, E7EPE6, O00125, O60916, Q13237
      UniProtKB/TrEMBL
      A0A140VJM3

    3. XM_054350506.1 → XP_054206481.1  cGMP-dependent protein kinase 2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13237.1 GenPept UniProtKB/Swiss-Prot:Q13237

    Gene LinkOut

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