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Protein

cGMP-dependent protein kinase 2

Gene

PRKG2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Crucial regulator of intestinal secretion and bone growth (By similarity). Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum (By similarity). Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By similarity). Acts as regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Binding of cGMP results in enzyme activation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei347cAMP or cGMP 21 PublicationImported1
Binding sitei412cAMP or cGMP 21 PublicationImported1
Binding sitei415cAMP or cGMP 21 PublicationImported1
Binding sitei482ATPPROSITE-ProRule annotation1
Active sitei576Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi232 – 235cAMP or cGMP 1Combined sources1 Publication4
Nucleotide bindingi242 – 243cAMP or cGMP 1Combined sources1 Publication2
Nucleotide bindingi357 – 359cAMP or cGMP 2Combined sources1 Publication3
Nucleotide bindingi366 – 367cAMP or cGMP 2Combined sources1 Publication2
Nucleotide bindingi459 – 467ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cGMP binding Source: UniProtKB-KW
  • cGMP-dependent protein kinase activity Source: Reactome
  • protein kinase activity Source: ProtInc

GO - Biological processi

  • peptidyl-serine autophosphorylation Source: Ensembl
  • protein phosphorylation Source: ProtInc
  • protein targeting to plasma membrane Source: Ensembl
  • regulation of nitric-oxide synthase activity Source: Reactome
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, cGMP, cGMP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.12. 2681.
ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-HSA-4086398. Ca2+ pathway.
R-HSA-418457. cGMP effects.
SignaLinkiQ13237.
SIGNORiQ13237.

Names & Taxonomyi

Protein namesi
Recommended name:
cGMP-dependent protein kinase 2 (EC:2.7.11.12)
Short name:
cGK 2
Short name:
cGK2
Alternative name(s):
cGMP-dependent protein kinase II
Short name:
cGKII
Gene namesi
Name:PRKG2
Synonyms:PRKGR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:9416. PRKG2.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi412D → A: Reduces cGMP binding affinity; when associated with A-415. 1 Publication1
Mutagenesisi415R → A: Reduces cGMP binding affinity; when associated with A-412. 1 Publication1

Organism-specific databases

DisGeNETi5593.
OpenTargetsiENSG00000138669.
PharmGKBiPA33778.

Chemistry databases

ChEMBLiCHEMBL2896.
GuidetoPHARMACOLOGYi1493.

Polymorphism and mutation databases

DMDMi6226833.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000861232 – 762cGMP-dependent protein kinase 2Add BLAST761

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei110PhosphoserineBy similarity1
Modified residuei117PhosphoserineBy similarity1
Modified residuei431PhosphoserineBy similarity1
Modified residuei609PhosphothreonineBy similarity1

Post-translational modificationi

Myristoylation mediates membrane localization.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiQ13237.
PeptideAtlasiQ13237.
PRIDEiQ13237.

PTM databases

iPTMnetiQ13237.
PhosphoSitePlusiQ13237.

Expressioni

Tissue specificityi

Highly concentrated in brain, lung and intestinal mucosa.

Gene expression databases

BgeeiENSG00000138669.
CleanExiHS_PRKG2.
ExpressionAtlasiQ13237. baseline and differential.
GenevisibleiQ13237. HS.

Organism-specific databases

HPAiCAB018739.
HPA007386.

Interactioni

Subunit structurei

Interacts with GRIA1/GLUR1.By similarity

Protein-protein interaction databases

BioGridi111579. 7 interactors.
IntActiQ13237. 3 interactors.
STRINGi9606.ENSP00000264399.

Chemistry databases

BindingDBiQ13237.

Structurei

Secondary structure

1762
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi153 – 164Combined sources12
Helixi169 – 171Combined sources3
Helixi174 – 183Combined sources10
Beta strandi185 – 189Combined sources5
Beta strandi194 – 196Combined sources3
Beta strandi204 – 211Combined sources8
Beta strandi213 – 217Combined sources5
Beta strandi220 – 224Combined sources5
Beta strandi230 – 232Combined sources3
Helixi233 – 238Combined sources6
Beta strandi243 – 250Combined sources8
Beta strandi252 – 258Combined sources7
Helixi259 – 266Combined sources8
Helixi270 – 283Combined sources14
Helixi285 – 287Combined sources3
Helixi292 – 301Combined sources10
Beta strandi303 – 307Combined sources5
Beta strandi312 – 314Combined sources3
Beta strandi323 – 335Combined sources13
Beta strandi344 – 350Combined sources7
Helixi357 – 362Combined sources6
Beta strandi368 – 372Combined sources5
Beta strandi377 – 382Combined sources6
Helixi384 – 389Combined sources6
Turni390 – 393Combined sources4
Helixi395 – 415Combined sources21

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5BV6X-ray1.94A269-418[»]
5C6CX-ray2.05A/B137-277[»]
5C8WX-ray1.80A/B/C/D/E/F137-277[»]
ProteinModelPortaliQ13237.
SMRiQ13237.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini453 – 711Protein kinasePROSITE-ProRule annotationAdd BLAST259
Domaini712 – 762AGC-kinase C-terminalAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni168 – 283cGMP-binding, high affinity; cAMP-binding, moderate affinity1 PublicationAdd BLAST116
Regioni286 – 416cGMP-binding, high affinity; cAMP-binding, low affinity1 PublicationAdd BLAST131

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili23 – 85Sequence analysisAdd BLAST63

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiQ13237.
KOiK19477.
OMAiELQSKCI.
OrthoDBiEOG091G0S9R.
PhylomeDBiQ13237.
TreeFamiTF313261.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR002374. cGMP_dep_kinase.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014710. RmlC-like_jellyroll.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00027. cNMP_binding. 2 hits.
PF00069. Pkinase. 1 hit.
PIRSFiPIRSF000559. cGMP-dep_kinase. 1 hit.
PRINTSiPR00104. CGMPKINASE.
SMARTiView protein in SMART
SM00100. cNMP. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF51206. SSF51206. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13237-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGNGSVKPKH SKHPDGHSGN LTTDALRNKV TELERELRRK DAEIQEREYH
60 70 80 90 100
LKELREQLSK QTVAIAELTE ELQNKCIQLN KLQDVVHMQG GSPLQASPDK
110 120 130 140 150
VPLEVHRKTS GLVSLHSRRG AKAGVSAEPT TRTYDLNKPP EFSFEKARVR
160 170 180 190 200
KDSSEKKLIT DALNKNQFLK RLDPQQIKDM VECMYGRNYQ QGSYIIKQGE
210 220 230 240 250
PGNHIFVLAE GRLEVFQGEK LLSSIPMWTT FGELAILYNC TRTASVKAIT
260 270 280 290 300
NVKTWALDRE VFQNIMRRTA QARDEQYRNF LRSVSLLKNL PEDKLTKIID
310 320 330 340 350
CLEVEYYDKG DYIIREGEEG STFFILAKGK VKVTQSTEGH DQPQLIKTLQ
360 370 380 390 400
KGEYFGEKAL ISDDVRSANI IAEENDVACL VIDRETFNQT VGTFEELQKY
410 420 430 440 450
LEGYVANLNR DDEKRHAKRS MSNWKLSKAL SLEMIQLKEK VARFSSSSPF
460 470 480 490 500
QNLEIIATLG VGGFGRVELV KVKNENVAFA MKCIRKKHIV DTKQQEHVYS
510 520 530 540 550
EKRILEELCS PFIVKLYRTF KDNKYVYMLL EACLGGELWS ILRDRGSFDE
560 570 580 590 600
PTSKFCVACV TEAFDYLHRL GIIYRDLKPE NLILDAEGYL KLVDFGFAKK
610 620 630 640 650
IGSGQKTWTF CGTPEYVAPE VILNKGHDFS VDFWSLGILV YELLTGNPPF
660 670 680 690 700
SGVDQMMTYN LILKGIEKMD FPRKITRRPE DLIRRLCRQN PTERLGNLKN
710 720 730 740 750
GINDIKKHRW LNGFNWEGLK ARSLPSPLQR ELKGPIDHSY FDKYPPEKGM
760
PPDELSGWDK DF
Length:762
Mass (Da):87,432
Last modified:November 1, 1996 - v1
Checksum:iFA7BA149906B5996
GO
Isoform 2 (identifier: Q13237-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     441-469: Missing.

Note: No experimental confirmation available.
Show »
Length:733
Mass (Da):84,398
Checksum:i913712AC4EC4F8BC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57 – 58QL → HG in BAA18934 (PubMed:7498513).Curated2
Sequence conflicti154S → I in CAA76073 (PubMed:9535793).Curated1
Sequence conflicti388N → D in BAG60035 (PubMed:14702039).Curated1
Sequence conflicti460G → A in BAA18934 (PubMed:7498513).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05163322T → S. Corresponds to variant dbSNP:rs34956759Ensembl.1
Natural variantiVAR_040608106H → R1 PublicationCorresponds to variant dbSNP:rs34616910Ensembl.1
Natural variantiVAR_040609716W → R in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055121441 – 469Missing in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94612 mRNA. Translation: CAA64318.1.
D70899 mRNA. Translation: BAA18934.1.
AK297673 mRNA. Translation: BAG60035.1.
AC098819 Genomic DNA. No translation available.
AC139722 Genomic DNA. No translation available.
Y16106
, Y16107, Y16108, Y16109, Y16110, Y16111, Y16112, Y16113, Y16114, Y16115, Y16116, Y16117, Y16118, Y16119, Y16120, Y16121, Y16122, Y16123 Genomic DNA. Translation: CAA76073.1.
CCDSiCCDS3589.1. [Q13237-1]
CCDS64005.1. [Q13237-2]
PIRiS68217.
RefSeqiNP_001269409.1. NM_001282480.1.
NP_001269410.1. NM_001282481.1.
NP_001269411.1. NM_001282482.1.
NP_001269412.1. NM_001282483.1.
NP_001269414.1. NM_001282485.1. [Q13237-2]
NP_006250.1. NM_006259.2. [Q13237-1]
XP_005263183.1. XM_005263126.3. [Q13237-1]
UniGeneiHs.232044.
Hs.570833.
Hs.739943.

Genome annotation databases

EnsembliENST00000264399; ENSP00000264399; ENSG00000138669. [Q13237-1]
ENST00000395578; ENSP00000378945; ENSG00000138669. [Q13237-1]
ENST00000628926; ENSP00000486129; ENSG00000138669. [Q13237-2]
GeneIDi5593.
KEGGihsa:5593.
UCSCiuc003hmh.3. human. [Q13237-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94612 mRNA. Translation: CAA64318.1.
D70899 mRNA. Translation: BAA18934.1.
AK297673 mRNA. Translation: BAG60035.1.
AC098819 Genomic DNA. No translation available.
AC139722 Genomic DNA. No translation available.
Y16106
, Y16107, Y16108, Y16109, Y16110, Y16111, Y16112, Y16113, Y16114, Y16115, Y16116, Y16117, Y16118, Y16119, Y16120, Y16121, Y16122, Y16123 Genomic DNA. Translation: CAA76073.1.
CCDSiCCDS3589.1. [Q13237-1]
CCDS64005.1. [Q13237-2]
PIRiS68217.
RefSeqiNP_001269409.1. NM_001282480.1.
NP_001269410.1. NM_001282481.1.
NP_001269411.1. NM_001282482.1.
NP_001269412.1. NM_001282483.1.
NP_001269414.1. NM_001282485.1. [Q13237-2]
NP_006250.1. NM_006259.2. [Q13237-1]
XP_005263183.1. XM_005263126.3. [Q13237-1]
UniGeneiHs.232044.
Hs.570833.
Hs.739943.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5BV6X-ray1.94A269-418[»]
5C6CX-ray2.05A/B137-277[»]
5C8WX-ray1.80A/B/C/D/E/F137-277[»]
ProteinModelPortaliQ13237.
SMRiQ13237.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111579. 7 interactors.
IntActiQ13237. 3 interactors.
STRINGi9606.ENSP00000264399.

Chemistry databases

BindingDBiQ13237.
ChEMBLiCHEMBL2896.
GuidetoPHARMACOLOGYi1493.

PTM databases

iPTMnetiQ13237.
PhosphoSitePlusiQ13237.

Polymorphism and mutation databases

DMDMi6226833.

Proteomic databases

PaxDbiQ13237.
PeptideAtlasiQ13237.
PRIDEiQ13237.

Protocols and materials databases

DNASUi5593.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264399; ENSP00000264399; ENSG00000138669. [Q13237-1]
ENST00000395578; ENSP00000378945; ENSG00000138669. [Q13237-1]
ENST00000628926; ENSP00000486129; ENSG00000138669. [Q13237-2]
GeneIDi5593.
KEGGihsa:5593.
UCSCiuc003hmh.3. human. [Q13237-1]

Organism-specific databases

CTDi5593.
DisGeNETi5593.
GeneCardsiPRKG2.
HGNCiHGNC:9416. PRKG2.
HPAiCAB018739.
HPA007386.
MIMi601591. gene.
neXtProtiNX_Q13237.
OpenTargetsiENSG00000138669.
PharmGKBiPA33778.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiQ13237.
KOiK19477.
OMAiELQSKCI.
OrthoDBiEOG091G0S9R.
PhylomeDBiQ13237.
TreeFamiTF313261.

Enzyme and pathway databases

BRENDAi2.7.11.12. 2681.
ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-HSA-4086398. Ca2+ pathway.
R-HSA-418457. cGMP effects.
SignaLinkiQ13237.
SIGNORiQ13237.

Miscellaneous databases

GenomeRNAii5593.
PROiPR:Q13237.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138669.
CleanExiHS_PRKG2.
ExpressionAtlasiQ13237. baseline and differential.
GenevisibleiQ13237. HS.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR002374. cGMP_dep_kinase.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014710. RmlC-like_jellyroll.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00027. cNMP_binding. 2 hits.
PF00069. Pkinase. 1 hit.
PIRSFiPIRSF000559. cGMP-dep_kinase. 1 hit.
PRINTSiPR00104. CGMPKINASE.
SMARTiView protein in SMART
SM00100. cNMP. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF51206. SSF51206. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKGP2_HUMAN
AccessioniPrimary (citable) accession number: Q13237
Secondary accession number(s): B4DMX3
, E7EPE6, O00125, O60916
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: March 15, 2017
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.