EKS-HOS-00171

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00171

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/PKG	509.3	9.1E-153	349	607	259

Status

Reviewed

Ensembl Protein

ENSP00000363097

UniProt Accession

Q13976; E2PU10; P14619; Q5JSJ6; Q6P5T7;

Protein Name

cGMP-dependent protein kinase 1

Protein Synonyms/Alias

cGK 1; cGK1; cGMP-dependent protein kinase I; cGKI;

Gene Name

PRKG1

Gene Synonyms/Alias

PRKG1; PRKG1B, PRKGR1A, PRKGR1B;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000185532	ENSP00000363086	ENST00000373975
ENSG00000185532	ENSP00000363087	ENST00000373976
ENSG00000185532	ENSP00000384200	ENST00000401604
ENSG00000185532	ENSP00000363097	ENST00000373985
ENSG00000185532	ENSP00000363092	ENST00000373980

Organism

Homo sapiens

Functional Description

Serine/threonine protein kinasethat acts as key mediatorof 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. Smoth 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 Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) 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.

Protein Length

659

Protein Sequence
(FASTA)

MLKEERIKEL EKRLSEKEEE IQELKRKLHK CQSVLPVPST HIGPRTTRAQ GISAEPQTYR 60

SFHDLRQAFR KFTKSERSKD LIKEAILDND FMKNLELSQI QEIVDCMYPV EYGKDSCIIK 120

EGDVGSLVYV MEDGKVEVTK EGVKLCTMGP GKVFGELAIL YNCTRTATVK TLVNVKLWAI 180

DRQCFQTIMM RTGLIKHTEY MEFLKSVPTF QSLPEEILSK LADVLEETHY ENGEYIIRQG 240

ARGDTFFIIS KGTVNVTRED SPSEDPVFLR TLGKGDWFGE KALQGEDVRT ANVIAAEAVT 300

CLVIDRDSFK HLIGGLDDVS NKAYEDAEAK AKYEAEAAFF ANLKLSDFNI IDTLGVGGFG 360

RVELVQLKSE ESKTFAMKIL KKRHIVDTRQ QEHIRSEKQI MQGAHSDFIV RLYRTFKDSK 420

YLYMLMEACL GGELWTILRD RGSFEDSTTR FYTACVVEAF AYLHSKGIIY RDLKPENLIL 480

DHRGYAKLVD FGFAKKIGFG KKTWTFCGTP EYVAPEIILN KGHDISADYW SLGILMYELL 540

TGSPPFSGPD PMKTYNIILR GIDMIEFPKK IAKNAANLIK KLCRDNPSER LGNLKNGVKD 600

IQKHKWFEGF NWEGLRKGTL TPPIIPSVAS PTDTSNFDSF PEDNDEPPPD DNSGWDIDF 659

Nucleotide Sequence
(FASTA)

ATGCTCAAGG AGGAGAGGAT CAAAGAGCTG GAGAAGCGGC TGTCAGAGAA GGAGGAAGAA 60

ATTCAGGAGC TGAAGAGGAA ACTCCACAAA TGCCAGTCGG TGCTCCCAGT GCCCTCGACC 120

CACATCGGCC CCCGGACCAC CCGGGCGCAG GGCATCTCGG CCGAGCCGCA GACGTACAGG 180

TCCTTCCACG ACCTCCGACA GGCATTCCGG AAGTTCACCA AGTCCGAAAG GTCCAAGGAT 240

CTTATAAAGG AAGCTATCCT TGACAATGAC TTTATGAAGA ACTTGGAGCT GTCGCAGATC 300

CAGGAGATTG TGGATTGTAT GTACCCGGTG GAGTATGGCA AGGACAGTTG CATCATCAAA 360

GAAGGAGACG TGGGGTCACT GGTGTATGTC ATGGAAGATG GTAAGGTTGA AGTTACAAAA 420

GAAGGTGTGA AGTTGTGTAC CATGGGTCCA GGAAAAGTGT TTGGGGAATT GGCTATTCTT 480

TACAACTGTA CCCGGACAGC GACCGTCAAG ACTCTTGTAA ATGTAAAACT CTGGGCCATT 540

GATCGACAAT GTTTTCAAAC AATAATGATG AGGACAGGAC TCATCAAGCA TACCGAGTAT 600

ATGGAATTTT TAAAAAGCGT TCCAACATTC CAGAGCCTTC CTGAAGAGAT CCTCAGCAAG 660

CTTGCTGATG TCCTTGAAGA GACCCACTAT GAAAATGGAG AATATATTAT CAGGCAAGGT 720

GCAAGAGGGG ACACCTTCTT TATCATCAGC AAAGGAACGG TAAATGTCAC TCGTGAAGAC 780

TCACCGAGTG AAGACCCAGT CTTTCTTAGA ACTTTAGGAA AAGGAGACTG GTTTGGAGAG 840

AAAGCCTTGC AGGGGGAAGA TGTGAGAACA GCAAACGTAA TTGCTGCAGA AGCTGTAACC 900

TGCCTTGTGA TTGACAGAGA CTCTTTTAAA CATTTGATTG GAGGGCTGGA TGATGTTTCT 960

AATAAAGCAT ATGAAGATGC AGAAGCTAAA GCAAAATATG AAGCTGAAGC GGCTTTCTTC 1020

GCCAACCTGA AGCTGTCTGA TTTCAACATC ATTGATACCC TTGGAGTTGG AGGTTTCGGA 1080

CGAGTAGAAC TGGTCCAGTT GAAAAGTGAA GAATCCAAAA CGTTTGCAAT GAAGATTCTC 1140

AAGAAACGTC ACATTGTGGA CACAAGACAG CAGGAGCACA TCCGCTCAGA GAAGCAGATC 1200

ATGCAGGGGG CTCATTCCGA TTTCATAGTG AGACTGTACA GAACATTTAA GGACAGCAAA 1260

TATTTGTATA TGTTGATGGA AGCTTGTCTA GGTGGAGAGC TCTGGACCAT TCTCAGGGAT 1320

AGAGGTTCGT TTGAAGATTC TACAACCAGA TTTTACACAG CATGTGTGGT AGAAGCTTTT 1380

GCCTATCTGC ATTCCAAAGG AATCATTTAC AGGGACCTCA AGCCAGAAAA TCTCATCCTA 1440

GATCACCGAG GTTATGCCAA ACTGGTTGAT TTTGGCTTTG CAAAGAAAAT AGGATTTGGA 1500

AAGAAAACAT GGACTTTTTG TGGGACTCCA GAGTATGTAG CCCCAGAGAT CATCCTGAAC 1560

AAAGGCCATG ACATTTCAGC CGACTACTGG TCACTGGGAA TCCTAATGTA TGAACTCCTG 1620

ACTGGCAGCC CACCTTTCTC AGGCCCAGAT CCTATGAAAA CCTATAACAT CATATTGAGG 1680

GGGATTGACA TGATAGAATT TCCAAAGAAG ATTGCCAAAA ATGCTGCTAA TTTAATTAAA 1740

AAACTATGCA GGGACAATCC ATCAGAAAGA TTAGGGAATT TGAAAAATGG AGTAAAAGAC 1800

ATTCAAAAGC ACAAATGGTT TGAGGGCTTT AACTGGGAAG GCTTAAGAAA AGGTACCTTG 1860

ACACCTCCTA TAATACCAAG TGTTGCATCA CCCACAGACA CAAGTAATTT TGACAGTTTC 1920

CCTGAGGACA ACGATGAACC ACCACCTGAT GACAACTCAG GATGGGATAT AGACTTCTAA 1980

Domain Profile

S: 2     kviatlgvggfgrvelvkvksdeskafalkilkkkhivdtkqqehvlsekrileeaksdf  61

         ++i+tlgvggfgrvelv++ks+esk+fa+kilkk+hivdt+qqeh++sek+i++ a+sdf

Q: 349   NIIDTLGVGGFGRVELVQLKSEESKTFAMKILKKRHIVDTRQQEHIRSEKQIMQGAHSDF  408

         79**********************************************************

S: 62    ivklyrtfkdekyvyllleaclggelwtilrdrgsfddktakfivacvvealeylhskni  121

         iv+lyrtfkd+ky+y+l+eaclggelwtilrdrgsf+d+t++f++acvvea++ylhsk+i

Q: 409   IVRLYRTFKDSKYLYMLMEACLGGELWTILRDRGSFEDSTTRFYTACVVEAFAYLHSKGI  468

         ************************************************************

S: 122   iyrdlkpenllldeegylklvdfgfakklksgkktwtfcgtpeyvapeiilnkghdlsvd  181

         iyrdlkpenl+ld++gy+klvdfgfakk++ gkktwtfcgtpeyvapeiilnkghd+s+d

Q: 469   IYRDLKPENLILDHRGYAKLVDFGFAKKIGFGKKTWTFCGTPEYVAPEIILNKGHDISAD  528

         ************************************************************

S: 182   ywalgilvyelltgkppfsgvdplktynlilkgidklelprkitkeaedlikklcrdnpa  241

         yw+lgil+yelltg+ppfsg+dp+ktyn+il+gid++e+p+ki+k+a++likklcrdnp+

Q: 529   YWSLGILMYELLTGSPPFSGPDPMKTYNIILRGIDMIEFPKKIAKNAANLIKKLCRDNPS  588

         ************************************************************

S: 242   erlgylkggikdikkhkwf  260

         erlg+lk+g+kdi+khkwf

Q: 589   ERLGNLKNGVKDIQKHKWF  607

         ******************9

Domain Sequence
(FASTA)

NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT RQQEHIRSEK QIMQGAHSDF 60

IVRLYRTFKD SKYLYMLMEA CLGGELWTIL RDRGSFEDST TRFYTACVVE AFAYLHSKGI 120

IYRDLKPENL ILDHRGYAKL VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD 180

YWSLGILMYE LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS 240

ERLGNLKNGV KDIQKHKWF 259

Keyword

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding; cGMP; cGMP-binding; Coiled coil; Complete proteome; Cytoplasm; Disulfide bond; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Choloepus hoffmanni"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pteropus vampyrus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005794	; C:Golgi apparatus
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0005246	; F:calcium channel regulator activity
GO:0030553	; F:cGMP binding
GO:0004692	; F:cGMP-dependent protein kinase activity
GO:0030036	; P:actin cytoskeleton organization
GO:0007596	; P:blood coagulation
GO:0016358	; P:dendrite development
GO:0030900	; P:forebrain development
GO:0090331	; P:negative regulation of platelet aggregation
GO:0001764	; P:neuron migration
GO:0043087	; P:regulation of GTPase activity
GO:0007165	; P:signal transduction

KEGG

hsa:5592

;

InterPros

IPR000961	; AGC-kinase_C.
IPR016232	; cGMP-dependent_protein_kinase.
IPR002374	; cGMP_dep_kinase.
IPR018490	; cNMP-bd-like.
IPR018488	; cNMP-bd_CS.
IPR000595	; cNMP-bd_dom.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR014710	; RmlC-like_jellyroll.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00027	; cNMP_binding; 2.
PF00069	; Pkinase; 1.

SMARTs

SM00100	; cNMP; 2.
SM00133	; S_TK_X; 1.
SM00220	; S_TKc; 1.

Prosites

PS51285	; AGC_KINASE_CTER; 1.
PS00888	; CNMP_BINDING_1; 2.
PS00889	; CNMP_BINDING_2; 2.
PS50042	; CNMP_BINDING_3; 2.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

PR00104

; CGMPKINASE.

Created Date

20-Feb-2013