EKS-MUM-00170

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00170

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/PKG	509.2	4.6E-153	361	619	259

Status

Reviewed

Ensembl Protein

ENSMUSP00000067576

UniProt Accession

P0C605; Q14DK6; Q9Z0Z0;

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
ENSMUSG00000052920	ENSMUSP00000067576	ENSMUST00000065067
ENSMUSG00000052920	ENSMUSP00000073268	ENSMUST00000073581

Organism

Mus musculus

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

671

Protein Sequence
(FASTA)

MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP STHIGPRTTR 60

AQGISAEPQT YRSFHDLRQA FRKFTKSERS KDLIKEAILD NDFMKNLELS QIQEIVDCMY 120

PVEYGKDSCI IKEGDVGSLV YVMEDGKVEV TKEGVKLCTM GPGKVFGELA ILYNCTRTAT 180

VKTLVNVKLW AIDRQCFQTI MMRTGLIKHT EYMEFLKSVP TFQSLPDEIL SKLADVLEET 240

HYENGEYIIR QGARGDTFFI ISKGQVNVTR EDSPSEDPVF LRTLGKGDWF GEKALQGEDV 300

RTANVIAAEA VTCLVIDRDS FKHLIGGLDD VSNKAYEDAE AKAKYEAEAA FFANLKLSDF 360

NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT RQQEHIRSEK QIMQGAHSDF 420

IVRLYRTFKD SKYLYMLMEA CLGGELWTIL RDRGSFEDST TRFYTACVVE AFAYLHSKGI 480

IYRDLKPENL ILDHRGYAKL VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD 540

YWSLGILMYE LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS 600

ERLGNLKNGV KDIQKHKWFE GFNWEGLRKG TLTPPIIPSV ASPTDTSNFD SFPEDSDEPP 660

PDDNSGWDID F 671

Nucleotide Sequence
(FASTA)

ATGAGCGAAC TGGAGGAAGA CTTTGCGAAG ATTCTCATGC TCAAGGAGGA GAGGATCAAA 60

GAGCTGGAGA AGCGGCTGTC AGAGAAGGAG GAAGAAATCC AGGAGCTGAA GAGGAAACTC 120

CACAAATGCC AGTCGGTGCT GCCGGTGCCC TCCACCCACA TCGGCCCGCG GACCACCCGG 180

GCGCAGGGCA TCTCCGCGGA GCCGCAGACC TACAGGTCCT TCCACGACCT GCGCCAGGCG 240

TTCCGGAAGT TCACTAAATC CGAGAGGTCG AAGGATCTCA TAAAGGAGGC TATCCTTGAC 300

AATGACTTCA TGAAGAACTT GGAGCTGTCA CAGATCCAGG AGATTGTGGA CTGTATGTAC 360

CCCGTGGAAT ACGGCAAGGA CAGCTGCATC ATCAAGGAAG GCGATGTGGG GTCACTGGTG 420

TACGTCATGG AAGATGGGAA GGTTGAAGTC ACAAAAGAAG GCGTGAAGCT CTGCACCATG 480

GGTCCTGGAA AAGTGTTCGG GGAGCTGGCT ATACTTTACA ACTGTACCCG GACAGCGACC 540

GTCAAGACTC TTGTAAATGT GAAACTCTGG GCCATCGATC GACAATGTTT TCAAACAATA 600

ATGATGAGGA CAGGACTCAT CAAGCATACC GAGTACATGG AATTTTTAAA AAGTGTTCCA 660

ACATTCCAGA GCCTTCCTGA TGAAATCCTC AGCAAGCTGG CTGATGTCCT CGAAGAGACC 720

CACTATGAAA ATGGAGAATA TATCATCAGG CAGGGTGCAA GAGGAGACAC CTTCTTCATC 780

ATCAGTAAAG GGCAGGTGAA TGTTACTCGA GAAGACTCAC CAAGTGAAGA CCCAGTCTTC 840

CTTAGAACTT TAGGGAAGGG AGATTGGTTT GGAGAGAAAG CGTTGCAGGG GGAGGATGTG 900

AGAACAGCAA ATGTTATTGC CGCAGAAGCT GTCACCTGCC TTGTGATTGA CAGAGACTCT 960

TTCAAGCATT TGATTGGAGG ACTGGACGAT GTTTCTAACA AAGCATATGA GGACGCAGAA 1020

GCAAAAGCAA AATATGAAGC CGAAGCTGCC TTCTTCGCCA ACCTGAAGCT GTCTGATTTC 1080

AACATCATTG ACACCCTTGG AGTTGGAGGT TTCGGACGAG TAGAGCTGGT CCAGTTGAAA 1140

AGTGAAGAAT CCAAAACATT TGCAATGAAG ATCCTCAAGA AACGCCACAT TGTGGACACC 1200

AGACAGCAGG AGCACATCCG CTCAGAGAAG CAGATCATGC AGGGGGCTCA TTCTGACTTC 1260

ATTGTGAGGC TGTACAGGAC ATTTAAAGAC AGCAAATACT TGTATATGTT GATGGAAGCG 1320

TGCCTGGGTG GAGAGCTCTG GACTATTCTC AGGGATAGGG GTTCGTTTGA AGACTCAACA 1380

ACCAGGTTTT ACACTGCATG TGTGGTAGAA GCATTCGCCT ATCTGCATTC CAAAGGAATC 1440

ATTTACAGGG ACCTCAAGCC GGAGAATCTC ATCCTAGATC ATCGAGGCTA TGCCAAACTG 1500

GTTGACTTTG GCTTTGCAAA GAAAATAGGA TTTGGAAAGA AAACATGGAC TTTTTGTGGG 1560

ACTCCAGAAT ATGTAGCCCC AGAGATCATC CTGAACAAAG GCCATGACAT TTCAGCTGAC 1620

TACTGGTCAC TAGGAATTCT GATGTATGAG CTTCTGACTG GCAGCCCACC TTTCTCAGGC 1680

CCAGATCCAA TGAAAACCTA CAATATCATA CTGCGGGGGA TTGACATGAT AGAATTTCCA 1740

AAGAAGATTG CAAAAAATGC TGCTAATTTA ATTAAAAAAC TATGCAGGGA CAACCCATCA 1800

GAGAGGTTAG GAAATTTGAA AAACGGAGTC AAAGACATTC AGAAACACAA GTGGTTTGAG 1860

GGCTTTAATT GGGAAGGCTT AAGAAAAGGC ACCTTGACAC CTCCCATAAT TCCAAGTGTT 1920

GCGTCACCCA CAGACACAAG CAATTTTGAC AGTTTCCCTG AGGACAGCGA TGAGCCACCA 1980

CCTGATGACA ACTCAGGCTG GGACATAGAC TTCTAA 2016

Domain Profile

S: 2     kviatlgvggfgrvelvkvksdeskafalkilkkkhivdtkqqehvlsekrileeaksdf  61

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

Q: 361   NIIDTLGVGGFGRVELVQLKSEESKTFAMKILKKRHIVDTRQQEHIRSEKQIMQGAHSDF  420

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

S: 62    ivklyrtfkdekyvyllleaclggelwtilrdrgsfddktakfivacvvealeylhskni  121

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

Q: 421   IVRLYRTFKDSKYLYMLMEACLGGELWTILRDRGSFEDSTTRFYTACVVEAFAYLHSKGI  480

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

S: 122   iyrdlkpenllldeegylklvdfgfakklksgkktwtfcgtpeyvapeiilnkghdlsvd  181

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

Q: 481   IYRDLKPENLILDHRGYAKLVDFGFAKKIGFGKKTWTFCGTPEYVAPEIILNKGHDISAD  540

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

S: 182   ywalgilvyelltgkppfsgvdplktynlilkgidklelprkitkeaedlikklcrdnpa  241

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

Q: 541   YWSLGILMYELLTGSPPFSGPDPMKTYNIILRGIDMIEFPKKIAKNAANLIKKLCRDNPS  600

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

S: 242   erlgylkggikdikkhkwf  260

         erlg+lk+g+kdi+khkwf

Q: 601   ERLGNLKNGVKDIQKHKWF  619

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

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

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>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"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

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: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

mmu:19091

;

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