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P51817 (PRKX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-dependent protein kinase catalytic subunit PRKX

Short name=PrKX
Short name=Protein kinase X
Short name=Protein kinase X-linked
Short name=Serine/threonine-protein kinase PRKX
EC=2.7.11.1
Alternative name(s):
Protein kinase PKX1
Gene names
Name:PRKX
Synonyms:PKX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length358 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.5 Ref.6

Enzyme regulation

Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates. Ref.5 Ref.6 Ref.12

Subunit structure

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). Ref.5 Ref.9 Ref.10 Ref.11 Ref.12

Subcellular location

Cytoplasm. Nucleus. Note: cAMP induces nuclear translocation. Ref.5 Ref.6 Ref.9

Tissue specificity

Widely expressed (at protein level). Specifically expressed in blood by macrophages and granulocytes according to Ref.4. Ref.1 Ref.4 Ref.7 Ref.8

Developmental stage

Expression is developmentally regulated being high and specific in a wide range of developing tissues including liver, kidney, brain and pancreas (at protein level). Ref.6 Ref.7 Ref.8

Induction

Up-regulated by phorbol 12-myristate 13-acetate (PMA). Ref.4 Ref.5 Ref.6 Ref.9 Ref.12

Post-translational modification

Phosphorylated; autophosphorylates in vitro. Ref.5 Ref.9

Involvement in disease

A chromosomal aberration involving PRKX is a cause of sex reversal disorder. Translocation t(X;Y)(p22;p11) with PRKY. Chromosomal translocations proximal to PRKY account for about 30% of the cases of sex reversal disorder in XX males and XY females.

Sequence similarities

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

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Biophysicochemical properties

Kinetic parameters:

KM=127 µM for ATP (in the presence of 10 mM magnesium chloride) Ref.5 Ref.6

KM=58 µM for kemptide (in the presence of 10 mM magnesium chloride)

KM=6.7 µM for kemptide (in the presence of 1 µM Br-cAMP at 30 degrees Celsius)

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   LigandATP-binding
cAMP
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from mutant phenotype Ref.13. Source: UniProtKB

cell adhesion

Inferred from mutant phenotype Ref.13. Source: UniProtKB

cell-substrate adhesion

Inferred from mutant phenotype Ref.9. Source: UniProtKB

endothelial cell migration

Inferred from mutant phenotype Ref.13. Source: UniProtKB

endothelial cell proliferation

Inferred from mutant phenotype Ref.13. Source: UniProtKB

epithelial tube morphogenesis

Inferred from direct assay Ref.10. Source: UniProtKB

kidney morphogenesis

Inferred from direct assay Ref.10. Source: UniProtKB

myeloid cell differentiation

Inferred from direct assay Ref.4. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.5Ref.9. Source: UniProtKB

regulation of cell adhesion

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of cell migration

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of epithelial cell differentiation involved in kidney development

Inferred from direct assay Ref.10. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.5Ref.13. Source: UniProtKB

nucleus

Inferred from direct assay Ref.5Ref.9Ref.13. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cAMP-dependent protein kinase activity

Inferred from direct assay Ref.5Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 358358cAMP-dependent protein kinase catalytic subunit PRKX
PRO_0000086582

Regions

Domain49 – 303255Protein kinase
Domain304 – 35855AGC-kinase C-terminal
Nucleotide binding55 – 639ATP By similarity

Sites

Active site1721Proton acceptor By similarity
Binding site781ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.14

Natural variations

Natural variant431V → A.
Corresponds to variant rs3752362 [ dbSNP | Ensembl ].
VAR_061744

Experimental info

Mutagenesis781K → R: Loss of function. Ref.6
Mutagenesis931H → Q: Constitutive kinase activity; when associated with R-202. Ref.7
Mutagenesis2021W → R: Constitutive kinase activity; when associated with Q-93. Ref.7
Mutagenesis2831R → L: Increases the affinity for PRKAR2A and PRKAR2B. Ref.12

Sequences

Sequence LengthMass (Da)Tools
P51817 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: B603834E3541CB56

FASTA35840,896
        10         20         30         40         50         60 
MEAPGLAQAA AAESDSRKVA EETPDGAPAL CPSPEALSPE PPVYSLQDFD TLATVGTGTF 

        70         80         90        100        110        120 
GRVHLVKEKT AKHFFALKVM SIPDVIRLKQ EQHVHNEKSV LKEVSHPFLI RLFWTWHDER 

       130        140        150        160        170        180 
FLYMLMEYVP GGELFSYLRN RGRFSSTTGL FYSAEIICAI EYLHSKEIVY RDLKPENILL 

       190        200        210        220        230        240 
DRDGHIKLTD FGFAKKLVDR TWTLCGTPEY LAPEVIQSKG HGRAVDWWAL GILIFEMLSG 

       250        260        270        280        290        300 
FPPFFDDNPF GIYQKILAGK IDFPRHLDFH VKDLIKKLLV VDRTRRLGNM KNGANDVKHH 

       310        320        330        340        350 
RWFRSVDWEA VPQRKLKPPI VPKIAGDGDT SNFETYPEND WDTAAPVPQK DLEIFKNF 

« Hide

References

« Hide 'large scale' references
[1]"The human protein kinase gene PKX1 on Xp22.3 displays Xp/Yp homology and is a site of chromosomal instability."
Klink A., Schiebel K., Winkelmann M., Rao E., Horsthemke B., Luedecke H.-J., Claussen U., Scherer G., Rappold G.
Hum. Mol. Genet. 4:869-878(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Fetal brain.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Blood.
[3]"Abnormal XY interchange between a novel isolated protein kinase gene, PRKY, and its homologue, PRKX, accounts for one third of all (Y+)XX males and (Y-)XY females."
Schiebel K., Winkelmann M., Mertz A., Xu X., Page D.C., Weil D., Petit C., Rappold G.A.
Hum. Mol. Genet. 6:1985-1989(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PRKY.
[4]"A lineage-specific protein kinase crucial for myeloid maturation."
Semizarov D., Glesne D., Laouar A., Schiebel K., Huberman E.
Proc. Natl. Acad. Sci. U.S.A. 95:15412-15417(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MYELOID CELL DIFFERENTIATION, TISSUE SPECIFICITY, INDUCTION BY PMA.
[5]"PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I."
Zimmermann B., Chiorini J.A., Ma Y., Kotin R.M., Herberg F.W.
J. Biol. Chem. 274:5370-5378(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, KINETIC PARAMETERS, INTERACTION WITH PRKAR1A AND PKI, ENZYME REGULATION BY PRKAR1A AND PKI, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION.
[6]"PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis."
Li X., Li H.P., Amsler K., Hyink D., Wilson P.D., Burrow C.R.
Proc. Natl. Acad. Sci. U.S.A. 99:9260-9265(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CREB-DEPENDENT TRANSCRIPTION, FUNCTION IN RENAL EPITHELIAL CELL MIGRATION AND TUBULOGENESIS, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-78, DEVELOPMENTAL STAGE.
[7]"Protein kinase X activates ureteric bud branching morphogenesis in developing mouse metanephric kidney."
Li X., Hyink D.P., Polgar K., Gusella G.L., Wilson P.D., Burrow C.R.
J. Am. Soc. Nephrol. 16:3543-3552(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEPHROGENESIS, MUTAGENESIS OF HIS-93 AND TRP-202, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[8]"Profiles of PrKX expression in developmental mouse embryo and human tissues."
Li W., Yu Z.X., Kotin R.M.
J. Histochem. Cytochem. 53:1003-1009(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[9]"Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation."
Glesne D., Huberman E.
Oncogene 25:4086-4098(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MYELOID CELL DIFFERENTIATION, FUNCTION IN PHOSPHORYLATION OF SMAD6, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH GPKOW; PRKAR1A; SMAD6, INDUCTION BY PMA.
[10]"Protein kinase X (PRKX) can rescue the effects of polycystic kidney disease-1 gene (PKD1) deficiency."
Li X., Burrow C.R., Polgar K., Hyink D.P., Gusella G.L., Wilson P.D.
Biochim. Biophys. Acta 1782:1-9(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEPHROGENESIS, FUNCTION IN PHOSPHORYLATION OF PKD1, INTERACTION WITH PKD1.
[11]"Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development."
Li X., Hyink D.P., Radbill B., Sudol M., Zhang H., Zheleznova N.N., Wilson P.D.
Kidney Int. 76:54-62(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEPHROGENESIS, INTERACTION WITH PIN1.
[12]"Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX) reveals the role of the catalytic subunit alphaH-alphaI loop."
Diskar M., Zenn H.M., Kaupisch A., Kaufholz M., Brockmeyer S., Sohmen D., Berrera M., Zaccolo M., Boshart M., Herberg F.W., Prinz A.
J. Biol. Chem. 285:35910-35918(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH PRKAR1A AND PRKAR1B, MUTAGENESIS OF ARG-283.
[13]"PRKX critically regulates endothelial cell proliferation, migration, and vascular-like structure formation."
Li X., Iomini C., Hyink D., Wilson P.D.
Dev. Biol. 356:475-485(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X85545 mRNA. Translation: CAA59733.1.
BC041073 mRNA. Translation: AAH41073.1.
CCDSCCDS14125.1.
PIRI38121.
RefSeqNP_005035.1. NM_005044.4.
XP_005274617.1. XM_005274560.1.
UniGeneHs.390788.

3D structure databases

ProteinModelPortalP51817.
SMRP51817. Positions 5-340.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111599. 4 interactions.
IntActP51817. 4 interactions.
STRING9606.ENSP00000262848.

Chemistry

BindingDBP51817.
ChEMBLCHEMBL5818.
GuidetoPHARMACOLOGY2175.

PTM databases

PhosphoSiteP51817.

Polymorphism databases

DMDM1709648.

Proteomic databases

MaxQBP51817.
PaxDbP51817.
PRIDEP51817.

Protocols and materials databases

DNASU5613.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262848; ENSP00000262848; ENSG00000183943.
GeneID5613.
KEGGhsa:5613.
UCSCuc010nde.3. human.

Organism-specific databases

CTD5613.
GeneCardsGC0XM003515.
H-InvDBHIX0202211.
HGNCHGNC:9441. PRKX.
HPAHPA015324.
MIM300083. gene.
neXtProtNX_P51817.
PharmGKBPA33786.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP51817.
KOK04345.
OMAHRWFRSI.
OrthoDBEOG7VX8WD.
PhylomeDBP51817.
TreeFamTF313399.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
SignaLinkP51817.

Gene expression databases

BgeeP51817.
CleanExHS_PRKX.
GenevestigatorP51817.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi5613.
NextBio21818.
PROP51817.
SOURCESearch...

Entry information

Entry namePRKX_HUMAN
AccessionPrimary (citable) accession number: P51817
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM