PRKG1

Functionⁱ

Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates MRVI1/IRAG and inhibits IP3-induced Ca²⁺ release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca²⁺ levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle.8 Publications

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.

Activity regulationⁱ

In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	282	cGMP 2Combined sources2 Publications	1
Binding siteⁱ	336	cAMP or cGMP 2Combined sources2 Publications	1
Binding siteⁱ	390	ATPPROSITE-ProRule annotation	1
Active siteⁱ	484	Proton acceptorPROSITE-ProRule annotation	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	167 – 170	cAMP or cGMP 1Combined sources1 Publication	4
Nucleotide bindingⁱ	177 – 178	cAMP or cGMP 1Combined sources1 Publication	2
Nucleotide bindingⁱ	291 – 294	cAMP or cGMP 2Combined sources2 Publications	4
Nucleotide bindingⁱ	301 – 302	cAMP or cGMP 2Combined sources2 Publications	2
Nucleotide bindingⁱ	366 – 374	ATPPROSITE-ProRule annotation	9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
calcium channel regulator activity
Source: UniProtKB
Inferred from direct assayⁱ
- 21402151
cGMP binding Source: UniProtKB-KW
cGMP-dependent protein kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 21402151
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 20826808
- 27066748
protein kinase activity
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 25447536
protein serine/threonine kinase activity Source: Reactome

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

actin cytoskeleton organization
Source: ProtInc
Traceable author statementⁱ
- 10851246
cGMP-mediated signaling Source: Ensembl
dendrite development Source: Ensembl
forebrain development Source: Ensembl
negative regulation of platelet aggregation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16990611
negative regulation of vascular associated smooth muscle cell migration
Source: BHF-UCL
Inferred from direct assayⁱ
- 25447536
negative regulation of vascular smooth muscle cell proliferation
Source: BHF-UCL
Inferred from direct assayⁱ
- 25447536
neuron migration Source: Ensembl
protein phosphorylation
Source: ProtInc
Traceable author statementⁱ
- 10851246
regulation of GTPase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 14608379
relaxation of vascular smooth muscle Source: Ensembl
signal transduction
Source: ProtInc
Traceable author statementⁱ
- 2792381

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Allosteric enzyme, Kinase, Serine/threonine-protein kinase, Transferase
Ligand	ATP-binding, cGMP, cGMP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.11.12 2681
Reactomeⁱ	R-HSA-392517 Rap1 signalling R-HSA-4086398 Ca2+ pathway R-HSA-418457 cGMP effects
SABIO-RKⁱ	Q13976
SignaLinkⁱ	Q13976
SIGNORⁱ	Q13976

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: cGMP-dependent protein kinase 1 (EC:2.7.11.12) Short name: cGK 1 Short name: cGK1 Alternative name(s): cGMP-dependent protein kinase I Short name: cGKI
Gene namesⁱ	Name:PRKG1 Synonyms:PRKG1B, PRKGR1A, PRKGR1B
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 10

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000185532.15
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:9414 PRKG1
MIMⁱ	176894 gene
neXtProtⁱ	NX_Q13976

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Aortic aneurysm, familial thoracic 8 (AAT8)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	12	L → A: Loss of binding to PPP1R12A. 1 Publication	1
Mutagenesisⁱ	19	I → A: Loss of binding to PPP1R12A. 1 Publication	1
Mutagenesisⁱ	26	L → P: Loss of binding to PPP1R12A. 1 Publication	1
Mutagenesisⁱ	33	I → A: Loss of binding to PPP1R12A. 1 Publication	1
Mutagenesisⁱ	40	L → A: Loss of binding to PPP1R12A. 1 Publication	1
Mutagenesisⁱ	281	L → A: Reduces cGMP binding affinity. 1 Publication	1
Mutagenesisⁱ	282	R → A: Reduces cGMP binding affinity. 1 Publication	1
Mutagenesisⁱ	302	T → A: Reduces cGMP binding affinity. 1 Publication	1
Mutagenesisⁱ	336	Y → A: Reduces cGMP binding affinity. 1 Publication	1

Keywords - Diseaseⁱ

Aortic aneurysm, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	5592
MalaCards human disease database More...MalaCardsⁱ	PRKG1
MIMⁱ	615436 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000185532
Orphanetⁱ	91387 Familial thoracic aortic aneurysm and aortic dissection
PharmGKBⁱ	PA33777

Chemistry databases

ChEMBLⁱ	CHEMBL4273
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1492

Polymorphism and mutation databases

BioMutaⁱ	PRKG1
DMDMⁱ	6225588

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000086115	2 – 671	cGMP-dependent protein kinase 1Add BLAST		670

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylserineCombined sources	1
Disulfide bondⁱ	43	InterchainBy similarity
Modified residueⁱ	59	Phosphothreonine; by autocatalysisBy similarity	1
Modified residueⁱ	515	PhosphothreonineBy similarity	1

Post-translational modificationⁱ

Autophosphorylation increases kinase activity.

65 kDa monomer is produced by proteolytic cleavage.By similarity

Keywords - PTMⁱ

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDⁱ	Q13976
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q13976
PeptideAtlas More...PeptideAtlasⁱ	Q13976
PRIDEⁱ	Q13976
ProteomicsDBⁱ	59781 59782 [Q13976-2]

PTM databases

iPTMnetⁱ	Q13976
PhosphoSitePlusⁱ	Q13976

Expressionⁱ

Tissue specificityⁱ

Primarily expressed in lung and placenta.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000185532 Expressed in 199 organ(s), highest expression level in biceps brachii
CleanExⁱ	HS_PRKG1
ExpressionAtlasⁱ	Q13976 baseline and differential
Genevisibleⁱ	Q13976 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB009629 HPA007699

HPAⁱ

CAB009629
HPA007699

Interactionⁱ

Subunit structureⁱ

Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP. Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1 (By similarity). Interacts with MRVI1. Forms a stable complex with ITPR1, MRVI1, and isoform beta of PRKG1. Interacts with TRPC7 (via ankyrin repeat domain). Isoform alpha interacts with RGS2. Interacts with GTF2I.By similarity9 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
BMPR2	Q13873	2	EBI-3952014,EBI-527196
FAM124A	Q86V42	3	EBI-3952014,EBI-744506
LMO2	P25791	3	EBI-3952014,EBI-739696
PDE5A	O76074	4	EBI-3952014,EBI-9023531
ZNF646	O15015	3	EBI-3952014,EBI-745608

GO - Molecular functionⁱ

identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 20826808
- 27066748

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	111578, 26 interactors
Database of interacting proteins More...DIPⁱ	DIP-41118N DIP-46288N
IntActⁱ	Q13976, 11 interactors
Molecular INTeraction database More...MINTⁱ	Q13976

Chemistry databases

BindingDBⁱ

Q13976

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	3 – 44	Combined sources	42
Helixⁱ	88 – 100	Combined sources	13
Turnⁱ	102 – 106	Combined sources	5
Helixⁱ	109 – 118	Combined sources	10
Beta strandⁱ	120 – 124	Combined sources	5
Beta strandⁱ	129 – 131	Combined sources	3
Beta strandⁱ	139 – 145	Combined sources	7
Beta strandⁱ	148 – 152	Combined sources	5
Beta strandⁱ	155 – 160	Combined sources	6
Beta strandⁱ	165 – 167	Combined sources	3
Helixⁱ	169 – 173	Combined sources	5
Beta strandⁱ	174 – 176	Combined sources	3
Beta strandⁱ	178 – 185	Combined sources	8
Beta strandⁱ	187 – 193	Combined sources	7
Helixⁱ	194 – 201	Combined sources	8
Helixⁱ	209 – 217	Combined sources	9
Helixⁱ	220 – 222	Combined sources	3
Helixⁱ	227 – 236	Combined sources	10
Beta strandⁱ	238 – 242	Combined sources	5
Beta strandⁱ	247 – 249	Combined sources	3
Beta strandⁱ	257 – 264	Combined sources	8
Beta strandⁱ	266 – 270	Combined sources	5
Beta strandⁱ	274 – 276	Combined sources	3
Beta strandⁱ	279 – 284	Combined sources	6
Helixⁱ	292 – 296	Combined sources	5
Beta strandⁱ	297 – 300	Combined sources	4
Beta strandⁱ	303 – 317	Combined sources	15
Helixⁱ	318 – 325	Combined sources	8
Turnⁱ	326 – 329	Combined sources	4
Helixⁱ	339 – 353	Combined sources	15
Helixⁱ	357 – 359	Combined sources	3
Beta strandⁱ	360 – 368	Combined sources	9
Beta strandⁱ	370 – 379	Combined sources	10
Beta strandⁱ	386 – 393	Combined sources	8
Helixⁱ	394 – 399	Combined sources	6
Helixⁱ	403 – 415	Combined sources	13
Beta strandⁱ	424 – 429	Combined sources	6
Beta strandⁱ	431 – 439	Combined sources	9
Helixⁱ	446 – 453	Combined sources	8
Helixⁱ	458 – 477	Combined sources	20
Helixⁱ	487 – 489	Combined sources	3
Beta strandⁱ	490 – 492	Combined sources	3
Beta strandⁱ	498 – 500	Combined sources	3
Helixⁱ	522 – 524	Combined sources	3
Helixⁱ	527 – 530	Combined sources	4
Helixⁱ	538 – 553	Combined sources	16
Helixⁱ	563 – 572	Combined sources	10
Helixⁱ	574 – 576	Combined sources	3
Helixⁱ	585 – 594	Combined sources	10
Helixⁱ	599 – 601	Combined sources	3
Turnⁱ	607 – 610	Combined sources	4
Helixⁱ	611 – 614	Combined sources	4
Helixⁱ	617 – 619	Combined sources	3
Helixⁱ	624 – 629	Combined sources	6
Turnⁱ	667 – 670	Combined sources	4

Show more details

3D structure databases

ProteinModelPortalⁱ	Q13976
SMRⁱ	Q13976
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q13976

EvolutionaryTraceⁱ

Q13976

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	360 – 619	Protein kinasePROSITE-ProRule annotationAdd BLAST		260
Domainⁱ	620 – 671	AGC-kinase C-terminalAdd BLAST		52

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	2 – 102	Required for dimerizationAdd BLAST	101
Regionⁱ	9 – 44	Leucine-zipperAdd BLAST	36
Regionⁱ	50 – 75	Autoinhibitory domainBy similarityAdd BLAST	26
Regionⁱ	103 – 220	cGMP-binding, high affinityAdd BLAST	118
Regionⁱ	221 – 341	cGMP-binding, low affinityAdd BLAST	121

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	2 – 59	1 PublicationAdd BLAST		58

Domainⁱ

Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity.

Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.Curated

Keywords - Domainⁱ

Coiled coil

Phylogenomic databases

Ensembl GeneTree More...GeneTreeⁱ	ENSGT00810000125385
HOGENOMⁱ	HOG000233033
HOVERGENⁱ	HBG062526
InParanoidⁱ	Q13976
KEGG Orthology (KO) More...KOⁱ	K07376
OMAⁱ	KGETYAE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0S9R
PhylomeDBⁱ	Q13976
TreeFamⁱ	TF313261

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00038 CAP_ED, 2 hits cd05572 STKc_cGK, 1 hit
Gene3Dⁱ	2.60.120.10, 2 hits
InterProⁱ	View protein in InterPro IPR000961 AGC-kinase_C IPR039811 cAMP/cGMP-dep_PK IPR002374 cGMP_dep_kinase IPR018490 cNMP-bd-like IPR018488 cNMP-bd_CS IPR000595 cNMP-bd_dom IPR011009 Kinase-like_dom_sf IPR031831 PKcGMP_CC IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR014710 RmlC-like_jellyroll IPR008271 Ser/Thr_kinase_AS IPR035014 STKc_cGK
PANTHERⁱ	PTHR24353 PTHR24353, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00027 cNMP_binding, 2 hits PF16808 PKcGMP_CC, 1 hit PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF000559 cGMP-dep_kinase, 1 hit
PRINTSⁱ	PR00104 CGMPKINASE
SMARTⁱ	View protein in SMART SM00100 cNMP, 2 hits SM00133 S_TK_X, 1 hit SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF51206 SSF51206, 2 hits SSF56112 SSF56112, 1 hit
PROSITEⁱ	View 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 (3+)ⁱ

Sequence statusⁱ: Complete.

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

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show all Align All

Isoform Alpha (identifier: Q13976-1) [UniParc]FASTA Add to basket

Also known as: CGK1-alpha

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
MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP 
        60         70         80         90        100
STHIGPRTTR AQGISAEPQT YRSFHDLRQA FRKFTKSERS KDLIKEAILD 
       110        120        130        140        150
NDFMKNLELS QIQEIVDCMY PVEYGKDSCI IKEGDVGSLV YVMEDGKVEV 
       160        170        180        190        200
TKEGVKLCTM GPGKVFGELA ILYNCTRTAT VKTLVNVKLW AIDRQCFQTI 
       210        220        230        240        250
MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET HYENGEYIIR 
       260        270        280        290        300
QGARGDTFFI ISKGTVNVTR EDSPSEDPVF LRTLGKGDWF GEKALQGEDV 
       310        320        330        340        350
RTANVIAAEA VTCLVIDRDS FKHLIGGLDD VSNKAYEDAE AKAKYEAEAA 
       360        370        380        390        400
FFANLKLSDF NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT 
       410        420        430        440        450
RQQEHIRSEK QIMQGAHSDF IVRLYRTFKD SKYLYMLMEA CLGGELWTIL 
       460        470        480        490        500
RDRGSFEDST TRFYTACVVE AFAYLHSKGI IYRDLKPENL ILDHRGYAKL 
       510        520        530        540        550
VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD YWSLGILMYE 
       560        570        580        590        600
LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS 
       610        620        630        640        650
ERLGNLKNGV KDIQKHKWFE GFNWEGLRKG TLTPPIIPSV ASPTDTSNFD 
       660        670 
SFPEDNDEPP PDDNSGWDID F

Length:671

Mass (Da):76,364

Last modified:January 23, 2007 - v3

Checksum:ⁱ51389502A5E5FBD2

GO

Isoform Beta (identifier: Q13976-2) [UniParc] [UniParc]FASTA Add to basket

Also known as: CGK1-beta

The sequence of this isoform differs from the canonical sequence as follows:
1-89: MSELEEDFAK...AFRKFTKSER → MGTLRDLQYA...TLPFYPKSPQ

« Hide

        10         20         30         40         50
MGTLRDLQYA LQEKIEELRQ RDALIDELEL ELDQKDELIQ KLQNELDKYR 
        60         70         80         90        100
SVIRPATQQA QKQSASTLQG EPRTKRQAIS AEPTAFDIQD LSHVTLPFYP 
       110        120        130        140        150
KSPQSKDLIK EAILDNDFMK NLELSQIQEI VDCMYPVEYG KDSCIIKEGD 
       160        170        180        190        200
VGSLVYVMED GKVEVTKEGV KLCTMGPGKV FGELAILYNC TRTATVKTLV 
       210        220        230        240        250
NVKLWAIDRQ CFQTIMMRTG LIKHTEYMEF LKSVPTFQSL PEEILSKLAD 
       260        270        280        290        300
VLEETHYENG EYIIRQGARG DTFFIISKGT VNVTREDSPS EDPVFLRTLG 
       310        320        330        340        350
KGDWFGEKAL QGEDVRTANV IAAEAVTCLV IDRDSFKHLI GGLDDVSNKA 
       360        370        380        390        400
YEDAEAKAKY EAEAAFFANL KLSDFNIIDT LGVGGFGRVE LVQLKSEESK 
       410        420        430        440        450
TFAMKILKKR HIVDTRQQEH IRSEKQIMQG AHSDFIVRLY RTFKDSKYLY 
       460        470        480        490        500
MLMEACLGGE LWTILRDRGS FEDSTTRFYT ACVVEAFAYL HSKGIIYRDL 
       510        520        530        540        550
KPENLILDHR GYAKLVDFGF AKKIGFGKKT WTFCGTPEYV APEIILNKGH 
       560        570        580        590        600
DISADYWSLG ILMYELLTGS PPFSGPDPMK TYNIILRGID MIEFPKKIAK 
       610        620        630        640        650
NAANLIKKLC RDNPSERLGN LKNGVKDIQK HKWFEGFNWE GLRKGTLTPP 
       660        670        680 
IIPSVASPTD TSNFDSFPED NDEPPPDDNS GWDIDF

Show »

Length:686

Mass (Da):77,804

Checksum:ⁱA097041AB284F1E6

GO

Isoform 3 (identifier: Q13976-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-15: MSELEEDFAKILMLK → MEKQNMFLHGSYILR
16-297: Missing.

« Hide

        10         20         30         40         50
MEKQNMFLHG SYILREDVRT ANVIAAEAVT CLVIDRDSFK HLIGGLDDVS 
        60         70         80         90        100
NKAYEDAEAK AKYEAEAAFF ANLKLSDFNI IDTLGVGGFG RVELVQLKSE 
       110        120        130        140        150
ESKTFAMKIL KKRHIVDTRQ QEHIRSEKQI MQGAHSDFIV RLYRTFKDSK 
       160        170        180        190        200
YLYMLMEACL GGELWTILRD RGSFEDSTTR FYTACVVEAF AYLHSKGIIY 
       210        220        230        240        250
RDLKPENLIL DHRGYAKLVD FGFAKKIGFG KKTWTFCGTP EYVAPEIILN 
       260        270        280        290        300
KGHDISADYW SLGILMYELL TGSPPFSGPD PMKTYNIILR GIDMIEFPKK 
       310        320        330        340        350
IAKNAANLIK KLCRDNPSER LGNLKNGVKD IQKHKWFEGF NWEGLRKGTL 
       360        370        380 
TPPIIPSVAS PTDTSNFDSF PEDNDEPPPD DNSGWDIDF

Note: No experimental confirmation available.

Show »

Length:389

Mass (Da):44,185

Checksum:ⁱ9792149F93773D55

GO

Computationally mapped potential isoform sequencesⁱ

There are 5 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

A0A0A0MSB3	A0A0A0MSB3_HUMAN	cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 1	PRKG1	459	Annotation score:
B1ALS0	B1ALS0_HUMAN	cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 1	PRKG1	312	Annotation score:
A0A2R8Y507	A0A2R8Y507_HUMAN	cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 1	PRKG1	323	Annotation score:
A0A2R8YE50	A0A2R8YE50_HUMAN	cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 1	PRKG1	260	Annotation score:
A0A2R8YH74	A0A2R8YH74_HUMAN	cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 1	PRKG1	287	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_070434	177	R → Q in AAT8; impairs cGMP binding; the mutant protein is constitutively active. 1 PublicationCorresponds to variant dbSNP:rs397515330EnsemblClinVar.	1
Natural variantⁱVAR_046773	249	I → V1 PublicationCorresponds to variant dbSNP:rs56082459Ensembl.	1
Natural variantⁱVAR_051632	267	N → S1 PublicationCorresponds to variant dbSNP:rs34997494Ensembl.	1
Natural variantⁱVAR_070435	474	Y → F1 PublicationCorresponds to variant dbSNP:rs149710600EnsemblClinVar.	1
Natural variantⁱVAR_070436	666	G → A1 PublicationCorresponds to variant dbSNP:rs750949508EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_038714	1 – 89	MSELE…TKSER → MGTLRDLQYALQEKIEELRQ RDALIDELELELDQKDELIQ KLQNELDKYRSVIRPATQQA QKQSASTLQGEPRTKRQAIS AEPTAFDIQDLSHVTLPFYP KSPQ in isoform Beta. 3 PublicationsAdd BLAST	89
Alternative sequenceⁱVSP_055541	1 – 15	MSELE…ILMLK → MEKQNMFLHGSYILR in isoform 3. 1 PublicationAdd BLAST	15
Alternative sequenceⁱVSP_055542	16 – 297	Missing in isoform 3. 1 PublicationAdd BLAST	282

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	Y07512 mRNA Translation: CAA68810.1 D45864 mRNA Translation: BAA08297.1 AK093436 mRNA Translation: BAG52715.1 EF560730 mRNA Translation: ABQ59040.1 Z92867 Z92885 Genomic DNA Translation: CAB07436.1 Z92868 Z92885 Genomic DNA Translation: CAB07437.1 AL391378 AC026228 Genomic DNA Translation: CAI39626.1 AL928686 AC022025 Genomic DNA Translation: CAI40743.1 AL157399 AC022537 Genomic DNA Translation: CAI41305.1 AL731537 AC009986 Genomic DNA Translation: CAI17115.1 AC068062 Genomic DNA No translation available. AC069079 Genomic DNA No translation available. AC073584 Genomic DNA No translation available. AL596105 Genomic DNA No translation available. AL607031 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54140.1 BC062688 mRNA Translation: AAH62688.1 BC127090 mRNA Translation: AAI27091.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS44399.1 [Q13976-1] CCDS7244.1 [Q13976-2]
PIRⁱ	S05702
NCBI Reference Sequences More...RefSeqⁱ	NP_001091982.1, NM_001098512.2 [Q13976-1] NP_006249.1, NM_006258.3 [Q13976-2]
UniGeneⁱ	Hs.407535 Hs.604483

Genome annotation databases

Ensemblⁱ	ENST00000373980; ENSP00000363092; ENSG00000185532 [Q13976-2] ENST00000373985; ENSP00000363097; ENSG00000185532 [Q13976-1] ENST00000401604; ENSP00000384200; ENSG00000185532 [Q13976-1] ENST00000646535; ENSP00000493966; ENSG00000185532 [Q13976-2]
GeneIDⁱ	5592
KEGGⁱ	hsa:5592
UCSC genome browser More...UCSCⁱ	uc001jjo.4 human [Q13976-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q13976	cGMP-dependent protein kinase		PANTR		671	UniRef100_Q13976
cGMP-dependent protein kinase		MACMU		671
cGMP-dependent protein kinase		COLAP		671
cGMP-dependent protein kinase		PONAB		671
cGMP-dependent protein kinase		PAPAN		671
+3
Q13976-2	cGMP-dependent protein kinase		PANTR		686	UniRef100_Q13976-2
cGMP-dependent protein kinase		MACMU		686
cGMP-dependent protein kinase		COLAP		686
cGMP-dependent protein kinase		PONAB		686
cGMP-dependent protein kinase		PAPAN		686
+13

Protein	Similar proteins		Species	Score	Length	Source
Q13976	cGMP-dependent protein kinase 1	)	BOVIN		671	UniRef90_Q13976
cGMP-dependent protein kinase 1		MOUSE		671
cGMP-dependent protein kinase 1		RABIT		671
cGMP-dependent protein kinase		PANTR		671
cGMP-dependent protein kinase		MACMU		671
+111
Q13976-2	cGMP-dependent protein kinase		PANTR		686	UniRef90_Q13976-2
cGMP-dependent protein kinase		MACMU		686
cGMP-dependent protein kinase		COLAP		686
cGMP-dependent protein kinase		PONAB		686
cGMP-dependent protein kinase		PAPAN		686
+201
Q13976-3	Uncharacterized protein		COLAP		476	UniRef90_Q13976-3
Protein kinase cGMP-dependent 1		CANLF		474
Uncharacterized protein		CALJA		467
cGMP-dependent protein kinase 1		AMAAE		466
Uncharacterized protein		RHIRO		463
+16

Protein	Similar proteins		Species	Score	Length	Source
Q13976	cGMP-dependent protein kinase 1	)	BOVIN		671	UniRef50_Q13976
cGMP-dependent protein kinase 1		RABIT		671
cGMP-dependent protein kinase 1		MOUSE		671
cGMP-dependent protein kinase		PANTR		671
cGMP-dependent protein kinase		MACMU		671
+626
Q13976-3	Uncharacterized protein		COLAP		476	UniRef50_Q13976-3
Protein kinase cGMP-dependent 1		CANLF		474
Uncharacterized protein		CALJA		467
cGMP-dependent protein kinase 1		AMAAE		466
Uncharacterized protein		RHIRO		463
+55

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	Y07512 mRNA Translation: CAA68810.1 D45864 mRNA Translation: BAA08297.1 AK093436 mRNA Translation: BAG52715.1 EF560730 mRNA Translation: ABQ59040.1 Z92867 Z92885 Genomic DNA Translation: CAB07436.1 Z92868 Z92885 Genomic DNA Translation: CAB07437.1 AL391378 AC026228 Genomic DNA Translation: CAI39626.1 AL928686 AC022025 Genomic DNA Translation: CAI40743.1 AL157399 AC022537 Genomic DNA Translation: CAI41305.1 AL731537 AC009986 Genomic DNA Translation: CAI17115.1 AC068062 Genomic DNA No translation available. AC069079 Genomic DNA No translation available. AC073584 Genomic DNA No translation available. AL596105 Genomic DNA No translation available. AL607031 Genomic DNA No translation available. CH471083 Genomic DNA Translation: EAW54140.1 BC062688 mRNA Translation: AAH62688.1 BC127090 mRNA Translation: AAI27091.1
CCDSⁱ	CCDS44399.1 [Q13976-1] CCDS7244.1 [Q13976-2]
PIRⁱ	S05702
RefSeqⁱ	NP_001091982.1, NM_001098512.2 [Q13976-1] NP_006249.1, NM_006258.3 [Q13976-2]
UniGeneⁱ	Hs.407535 Hs.604483

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1ZXA	NMR	-	A/B	2-59	[»]
	3NMD	X-ray	2.27	A/B/C/D/E	4-47	[»]
	3OCP	X-ray	2.49	A/B	84-212	[»]
	3OD0	X-ray	2.90	A/B	84-212	[»]
	3OGJ	X-ray	2.75	A/B/C/D	84-212	[»]
	4KU7	X-ray	1.65	A	204-354	[»]
	4KU8	X-ray	1.99	A/B/C	204-354	[»]
	4QX5	X-ray	1.32	A	204-354	[»]
	4QXK	Other	2.20	A	204-354	[»]
	4R4L	X-ray	2.25	A/B/C	2-48	[»]
	4R4M	X-ray	1.92	A/B/C	2-48	[»]
	4Z07	X-ray	2.50	A/C/E	84-336	[»]
	5J48	X-ray	1.49	A/B	204-336	[»]
	5JAX	X-ray	1.49	A	204-336	[»]
	5JD7	X-ray	1.75	A	204-336	[»]
	5L0N	X-ray	1.28	A	204-336	[»]
	6C0T	X-ray	1.98	A	327-671	[»]
ProteinModelPortalⁱ	Q13976
SMRⁱ	Q13976
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	111578, 26 interactors
DIPⁱ	DIP-41118N DIP-46288N
IntActⁱ	Q13976, 11 interactors
MINTⁱ	Q13976

Chemistry databases

BindingDBⁱ	Q13976
ChEMBLⁱ	CHEMBL4273
GuidetoPHARMACOLOGYⁱ	1492

PTM databases

iPTMnetⁱ	Q13976
PhosphoSitePlusⁱ	Q13976

Polymorphism and mutation databases

BioMutaⁱ	PRKG1
DMDMⁱ	6225588

Proteomic databases

EPDⁱ	Q13976
MaxQBⁱ	Q13976
PeptideAtlasⁱ	Q13976
PRIDEⁱ	Q13976
ProteomicsDBⁱ	59781 59782 [Q13976-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	5592
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000373980; ENSP00000363092; ENSG00000185532 [Q13976-2] ENST00000373985; ENSP00000363097; ENSG00000185532 [Q13976-1] ENST00000401604; ENSP00000384200; ENSG00000185532 [Q13976-1] ENST00000646535; ENSP00000493966; ENSG00000185532 [Q13976-2]
GeneIDⁱ	5592
KEGGⁱ	hsa:5592
UCSCⁱ	uc001jjo.4 human [Q13976-1]

Organism-specific databases

CTDⁱ	5592
DisGeNETⁱ	5592
EuPathDBⁱ	HostDB:ENSG00000185532.15
GeneCardsⁱ	PRKG1
HGNCⁱ	HGNC:9414 PRKG1
HPAⁱ	CAB009629 HPA007699
MalaCardsⁱ	PRKG1
MIMⁱ	176894 gene 615436 phenotype
neXtProtⁱ	NX_Q13976
OpenTargetsⁱ	ENSG00000185532
Orphanetⁱ	91387 Familial thoracic aortic aneurysm and aortic dissection
PharmGKBⁱ	PA33777
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

GeneTreeⁱ	ENSGT00810000125385
HOGENOMⁱ	HOG000233033
HOVERGENⁱ	HBG062526
InParanoidⁱ	Q13976
KOⁱ	K07376
OMAⁱ	KGETYAE
OrthoDBⁱ	EOG091G0S9R
PhylomeDBⁱ	Q13976
TreeFamⁱ	TF313261

Enzyme and pathway databases

BRENDAⁱ	2.7.11.12 2681
Reactomeⁱ	R-HSA-392517 Rap1 signalling R-HSA-4086398 Ca2+ pathway R-HSA-418457 cGMP effects
SABIO-RKⁱ	Q13976
SignaLinkⁱ	Q13976
SIGNORⁱ	Q13976

Miscellaneous databases

ChiTaRSⁱ	PRKG1 human
EvolutionaryTraceⁱ	Q13976
GeneWikiⁱ	PRKG1
GenomeRNAiⁱ	5592
Protein Ontology More...PROⁱ	PR:Q13976
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000185532 Expressed in 199 organ(s), highest expression level in biceps brachii
CleanExⁱ	HS_PRKG1
ExpressionAtlasⁱ	Q13976 baseline and differential
Genevisibleⁱ	Q13976 HS

Family and domain databases

CDDⁱ	cd00038 CAP_ED, 2 hits cd05572 STKc_cGK, 1 hit
Gene3Dⁱ	2.60.120.10, 2 hits
InterProⁱ	View protein in InterPro IPR000961 AGC-kinase_C IPR039811 cAMP/cGMP-dep_PK IPR002374 cGMP_dep_kinase IPR018490 cNMP-bd-like IPR018488 cNMP-bd_CS IPR000595 cNMP-bd_dom IPR011009 Kinase-like_dom_sf IPR031831 PKcGMP_CC IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR014710 RmlC-like_jellyroll IPR008271 Ser/Thr_kinase_AS IPR035014 STKc_cGK
PANTHERⁱ	PTHR24353 PTHR24353, 1 hit
Pfamⁱ	View protein in Pfam PF00027 cNMP_binding, 2 hits PF16808 PKcGMP_CC, 1 hit PF00069 Pkinase, 1 hit
PIRSFⁱ	PIRSF000559 cGMP-dep_kinase, 1 hit
PRINTSⁱ	PR00104 CGMPKINASE
SMARTⁱ	View protein in SMART SM00100 cNMP, 2 hits SM00133 S_TK_X, 1 hit SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF51206 SSF51206, 2 hits SSF56112 SSF56112, 1 hit
PROSITEⁱ	View 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
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	KGP1_HUMAN
Accessionⁱ	Q13976Primary (citable) accession number: Q13976 Secondary accession number(s): A5YM56 Q6P5T7
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
	Last sequence update:	January 23, 2007
	Last modified:	November 7, 2018
	This is version 189 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM
Human and mouse protein kinases
Human and mouse protein kinases: classification and index

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UniProtKB - Q13976 (KGP1_HUMAN)

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cGMP-dependent protein kinase 1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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Keywords - PTMi

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<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Keywords - Coding sequence diversityi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

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Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ