UniProtKB - P51817 (PRKX_HUMAN)
cAMP-dependent protein kinase catalytic subunit PRKX
PRKX
Functioni
Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation.
7 PublicationsCatalytic activityi
Activity regulationi
Kineticsi
- KM=127 µM for ATP (in the presence of 10 mM magnesium chloride)2 Publications
- KM=58 µM for kemptide (in the presence of 10 mM magnesium chloride)2 Publications
- KM=6.7 µM for kemptide (in the presence of 1 µM Br-cAMP at 30 degrees Celsius)2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 78 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 172 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 55 – 63 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cAMP-dependent protein kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
GO - Biological processi
- angiogenesis Source: UniProtKB
- cell adhesion Source: UniProtKB
- cell-substrate adhesion Source: UniProtKB
- endothelial cell migration Source: UniProtKB
- endothelial cell proliferation Source: UniProtKB
- epithelial tube morphogenesis Source: UniProtKB
- kidney morphogenesis Source: UniProtKB
- myeloid cell differentiation Source: UniProtKB
- peptidyl-serine phosphorylation Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- regulation of cell adhesion Source: UniProtKB
- regulation of cell migration Source: UniProtKB
- regulation of epithelial cell differentiation involved in kidney development Source: UniProtKB
- signal transduction Source: GO_Central
Keywordsi
Molecular function | Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Angiogenesis, Differentiation |
Ligand | ATP-binding, cAMP, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 2681 |
PathwayCommonsi | P51817 |
Reactomei | R-HSA-111931, PKA-mediated phosphorylation of CREB R-HSA-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-9664323, FCGR3A-mediated IL10 synthesis |
SABIO-RKi | P51817 |
SignaLinki | P51817 |
SIGNORi | P51817 |
Names & Taxonomyi
Protein namesi | Recommended name: cAMP-dependent protein kinase catalytic subunit PRKX (EC:2.7.11.1)Short name: PrKX Short name: Protein kinase X Short name: Protein kinase X-linked Short name: Serine/threonine-protein kinase PRKX Alternative name(s): Protein kinase PKX1 |
Gene namesi | Name:PRKX Synonyms:PKX1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9441, PRKX |
MIMi | 300083, gene |
neXtProti | NX_P51817 |
VEuPathDBi | HostDB:ENSG00000183943 |
Subcellular locationi
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cAMP-dependent protein kinase complex Source: GO_Central
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 78 | K → R: Loss of function. 1 Publication | 1 | |
Mutagenesisi | 93 | H → Q: Constitutive kinase activity; when associated with R-202. 1 Publication | 1 | |
Mutagenesisi | 202 | W → R: Constitutive kinase activity; when associated with Q-93. 1 Publication | 1 | |
Mutagenesisi | 283 | R → L: Increases the affinity for PRKAR2A and PRKAR2B. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 5613 |
OpenTargetsi | ENSG00000183943 |
PharmGKBi | PA33786 |
Miscellaneous databases
Pharosi | P51817, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5818 |
DrugCentrali | P51817 |
GuidetoPHARMACOLOGYi | 2175 |
Genetic variation databases
BioMutai | PRKX |
DMDMi | 1709648 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086582 | 1 – 358 | cAMP-dependent protein kinase catalytic subunit PRKXAdd BLAST | 358 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 203 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P51817 |
jPOSTi | P51817 |
MassIVEi | P51817 |
MaxQBi | P51817 |
PaxDbi | P51817 |
PeptideAtlasi | P51817 |
PRIDEi | P51817 |
ProteomicsDBi | 56426 |
PTM databases
iPTMneti | P51817 |
PhosphoSitePlusi | P51817 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSG00000183943, Expressed in subventricular zone (outer) (primate) and 192 other tissues |
ExpressionAtlasi | P51817, baseline and differential |
Genevisiblei | P51817, HS |
Organism-specific databases
HPAi | ENSG00000183943, Tissue enhanced (thyroid) |
Interactioni
Subunit structurei
Like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits and a dimer of regulatory subunits.
Interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other cAMP-dependent serine/threonine protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B.
Interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX.
Interacts with GPKOW.
Interacts with SMAD6.
Interacts with PKD1; involved in differentiation and controlled morphogenesis of the kidney.
Interacts with PIN1 (via WW domain).
5 PublicationsBinary interactionsi
P51817
With | #Exp. | IntAct |
---|---|---|
GPKOW [Q92917] | 2 | EBI-4302903,EBI-746309 |
HSP90AB1 [P08238] | 3 | EBI-4302903,EBI-352572 |
PRKAR1A [P10644] | 2 | EBI-4302903,EBI-476431 |
SMAD6 [O43541] | 5 | EBI-4302903,EBI-976374 |
Protein-protein interaction databases
BioGRIDi | 111599, 44 interactors |
IntActi | P51817, 16 interactors |
STRINGi | 9606.ENSP00000262848 |
Chemistry databases
BindingDBi | P51817 |
Miscellaneous databases
RNActi | P51817, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 49 – 303 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 255 | |
Domaini | 304 – 358 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 55 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 34 | DisorderedSequence analysisAdd BLAST | 34 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
GeneTreei | ENSGT00940000159832 |
HOGENOMi | CLU_000288_63_5_1 |
InParanoidi | P51817 |
OMAi | QEDPPRY |
OrthoDBi | 963519at2759 |
PhylomeDBi | P51817 |
TreeFami | TF313399 |
Family and domain databases
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MEAPGLAQAA AAESDSRKVA EETPDGAPAL CPSPEALSPE PPVYSLQDFD
60 70 80 90 100
TLATVGTGTF GRVHLVKEKT AKHFFALKVM SIPDVIRLKQ EQHVHNEKSV
110 120 130 140 150
LKEVSHPFLI RLFWTWHDER FLYMLMEYVP GGELFSYLRN RGRFSSTTGL
160 170 180 190 200
FYSAEIICAI EYLHSKEIVY RDLKPENILL DRDGHIKLTD FGFAKKLVDR
210 220 230 240 250
TWTLCGTPEY LAPEVIQSKG HGRAVDWWAL GILIFEMLSG FPPFFDDNPF
260 270 280 290 300
GIYQKILAGK IDFPRHLDFH VKDLIKKLLV VDRTRRLGNM KNGANDVKHH
310 320 330 340 350
RWFRSVDWEA VPQRKLKPPI VPKIAGDGDT SNFETYPEND WDTAAPVPQK
DLEIFKNF
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_061744 | 43 | V → A. Corresponds to variant dbSNP:rs3752362Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X85545 mRNA Translation: CAA59733.1 BC041073 mRNA Translation: AAH41073.1 |
CCDSi | CCDS14125.1 |
PIRi | I38121 |
RefSeqi | NP_005035.1, NM_005044.4 |
Genome annotation databases
Ensembli | ENST00000262848.6; ENSP00000262848.5; ENSG00000183943.6 |
GeneIDi | 5613 |
KEGGi | hsa:5613 |
MANE-Selecti | ENST00000262848.6; ENSP00000262848.5; NM_005044.5; NP_005035.1 |
UCSCi | uc010nde.4, human |
Keywords - Coding sequence diversityi
Chromosomal rearrangementSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X85545 mRNA Translation: CAA59733.1 BC041073 mRNA Translation: AAH41073.1 |
CCDSi | CCDS14125.1 |
PIRi | I38121 |
RefSeqi | NP_005035.1, NM_005044.4 |
3D structure databases
AlphaFoldDBi | P51817 |
SMRi | P51817 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 111599, 44 interactors |
IntActi | P51817, 16 interactors |
STRINGi | 9606.ENSP00000262848 |
Chemistry databases
BindingDBi | P51817 |
ChEMBLi | CHEMBL5818 |
DrugCentrali | P51817 |
GuidetoPHARMACOLOGYi | 2175 |
PTM databases
iPTMneti | P51817 |
PhosphoSitePlusi | P51817 |
Genetic variation databases
BioMutai | PRKX |
DMDMi | 1709648 |
Proteomic databases
EPDi | P51817 |
jPOSTi | P51817 |
MassIVEi | P51817 |
MaxQBi | P51817 |
PaxDbi | P51817 |
PeptideAtlasi | P51817 |
PRIDEi | P51817 |
ProteomicsDBi | 56426 |
Protocols and materials databases
Antibodypediai | 7924, 236 antibodies from 30 providers |
DNASUi | 5613 |
Genome annotation databases
Ensembli | ENST00000262848.6; ENSP00000262848.5; ENSG00000183943.6 |
GeneIDi | 5613 |
KEGGi | hsa:5613 |
MANE-Selecti | ENST00000262848.6; ENSP00000262848.5; NM_005044.5; NP_005035.1 |
UCSCi | uc010nde.4, human |
Organism-specific databases
CTDi | 5613 |
DisGeNETi | 5613 |
GeneCardsi | PRKX |
HGNCi | HGNC:9441, PRKX |
HPAi | ENSG00000183943, Tissue enhanced (thyroid) |
MIMi | 300083, gene |
neXtProti | NX_P51817 |
OpenTargetsi | ENSG00000183943 |
PharmGKBi | PA33786 |
VEuPathDBi | HostDB:ENSG00000183943 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
GeneTreei | ENSGT00940000159832 |
HOGENOMi | CLU_000288_63_5_1 |
InParanoidi | P51817 |
OMAi | QEDPPRY |
OrthoDBi | 963519at2759 |
PhylomeDBi | P51817 |
TreeFami | TF313399 |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 2681 |
PathwayCommonsi | P51817 |
Reactomei | R-HSA-111931, PKA-mediated phosphorylation of CREB R-HSA-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-9664323, FCGR3A-mediated IL10 synthesis |
SABIO-RKi | P51817 |
SignaLinki | P51817 |
SIGNORi | P51817 |
Miscellaneous databases
BioGRID-ORCSi | 5613, 8 hits in 731 CRISPR screens |
ChiTaRSi | PRKX, human |
GenomeRNAii | 5613 |
Pharosi | P51817, Tchem |
PROi | PR:P51817 |
RNActi | P51817, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000183943, Expressed in subventricular zone (outer) (primate) and 192 other tissues |
ExpressionAtlasi | P51817, baseline and differential |
Genevisiblei | P51817, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PRKX_HUMAN | |
Accessioni | P51817Primary (citable) accession number: P51817 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 185 of the entry and version 1 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
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families