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

Summary

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

Location:: 4q21.21

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (81087370..81217836, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (84417063..84547534, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (82008524..82136376, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Variable skeletal phenotypes associated with biallelic variants in PRKG2.
Title: Variable skeletal phenotypes associated with biallelic variants in PRKG2.
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.
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.
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.
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?
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.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4S1381 (e-PCR)
- UniSTS:65795

STS-X94612 (e-PCR)
- UniSTS:3392

D4S299 (e-PCR)
- UniSTS:24933

AFM318ZC9 (e-PCR)
- UniSTS:51424

SHGC-51635 (e-PCR)
- UniSTS:47078

SHGC-51140 (e-PCR)
- UniSTS:38631

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 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	IBA Inferred from Biological aspect of Ancestor more info
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

EC 2.7.11.12

NP_001269410.1

EC 2.7.11.12

NP_001269411.1

EC 2.7.11.12

NP_001269412.1

EC 2.7.11.12

NP_001269414.1

EC 2.7.11.12

NP_001350330.1

EC 2.7.11.12

NP_006250.1

EC 2.7.11.12

XP_016863904.2

EC 2.7.11.12

XP_016863905.2

EC 2.7.11.12

XP_016863907.1

EC 2.7.11.12

XP_047271919.1

EC 2.7.11.12

XP_054206479.1

EC 2.7.11.12

XP_054206480.1

EC 2.7.11.12

XP_054206481.1

EC 2.7.11.12

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)

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)
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)
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)
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)
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)
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)
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

81087370..81217836 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

B4DMX3, E7EPE6, O00125, O60916, Q13237

UniProtKB/TrEMBL

A0A140VJM3
XM_017008416.2 → XP_016863905.2 cGMP-dependent protein kinase 2 isoform X1

UniProtKB/Swiss-Prot

B4DMX3, E7EPE6, O00125, O60916, Q13237

UniProtKB/TrEMBL

A0A140VJM3
XM_047415963.1 → XP_047271919.1 cGMP-dependent protein kinase 2 isoform X1

UniProtKB/Swiss-Prot

B4DMX3, E7EPE6, O00125, O60916, Q13237

UniProtKB/TrEMBL

A0A140VJM3
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

NC_060928.1 Alternate T2T-CHM13v2.0

Range

84417063..84547534 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

B4DMX3, E7EPE6, O00125, O60916, Q13237

UniProtKB/TrEMBL

A0A140VJM3
XM_054350505.1 → XP_054206480.1 cGMP-dependent protein kinase 2 isoform X1

UniProtKB/Swiss-Prot

B4DMX3, E7EPE6, O00125, O60916, Q13237

UniProtKB/TrEMBL

A0A140VJM3
XM_054350506.1 → XP_054206481.1 cGMP-dependent protein kinase 2 isoform X2