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P51817

- PRKX_HUMAN

UniProt

P51817 - PRKX_HUMAN

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Protein

cAMP-dependent protein kinase catalytic subunit PRKX

Gene

PRKX

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Enzyme regulationi

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.3 Publications

Kineticsi

  1. KM=127 µM for ATP (in the presence of 10 mM magnesium chloride)2 Publications
  2. KM=58 µM for kemptide (in the presence of 10 mM magnesium chloride)2 Publications
  3. KM=6.7 µM for kemptide (in the presence of 1 µM Br-cAMP at 30 degrees Celsius)2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei78 – 781ATPPROSITE-ProRule annotation
Active sitei172 – 1721Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi55 – 639ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cAMP-dependent protein kinase activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. cell adhesion Source: UniProtKB
  3. cell-substrate adhesion Source: UniProtKB
  4. endothelial cell migration Source: UniProtKB
  5. endothelial cell proliferation Source: UniProtKB
  6. epithelial tube morphogenesis Source: UniProtKB
  7. kidney morphogenesis Source: UniProtKB
  8. myeloid cell differentiation Source: UniProtKB
  9. peptidyl-serine phosphorylation Source: UniProtKB
  10. protein autophosphorylation Source: UniProtKB
  11. regulation of cell adhesion Source: UniProtKB
  12. regulation of cell migration Source: UniProtKB
  13. regulation of epithelial cell differentiation involved in kidney development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Angiogenesis, Differentiation

Keywords - Ligandi

ATP-binding, cAMP, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
SignaLinkiP51817.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome X

Organism-specific databases

HGNCiHGNC:9441. PRKX.

Subcellular locationi

Cytoplasm. Nucleus
Note: cAMP induces nuclear translocation.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi78 – 781K → R: Loss of function. 1 Publication
Mutagenesisi93 – 931H → Q: Constitutive kinase activity; when associated with R-202. 1 Publication
Mutagenesisi202 – 2021W → R: Constitutive kinase activity; when associated with Q-93. 1 Publication
Mutagenesisi283 – 2831R → L: Increases the affinity for PRKAR2A and PRKAR2B. 1 Publication

Organism-specific databases

PharmGKBiPA33786.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 358358cAMP-dependent protein kinase catalytic subunit PRKXPRO_0000086582Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication

Post-translational modificationi

Phosphorylated; autophosphorylates in vitro.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP51817.
PaxDbiP51817.
PRIDEiP51817.

PTM databases

PhosphoSiteiP51817.

Expressioni

Tissue specificityi

Widely expressed (at protein level). Specifically expressed in blood by macrophages and granulocytes according to PubMed:9860982.4 Publications

Developmental stagei

Expression is developmentally regulated being high and specific in a wide range of developing tissues including liver, kidney, brain and pancreas (at protein level).3 Publications

Inductioni

Up-regulated by phorbol 12-myristate 13-acetate (PMA).2 Publications

Gene expression databases

BgeeiP51817.
CleanExiHS_PRKX.
GenevestigatoriP51817.

Organism-specific databases

HPAiHPA015324.

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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GPKOWQ929172EBI-4302903,EBI-746309
HSP90AB1P082382EBI-4302903,EBI-352572
PRKAR1AP106442EBI-4302903,EBI-476431
SMAD6O435415EBI-4302903,EBI-976374

Protein-protein interaction databases

BioGridi111599. 6 interactions.
IntActiP51817. 4 interactions.
STRINGi9606.ENSP00000262848.

Structurei

3D structure databases

ProteinModelPortaliP51817.
SMRiP51817. Positions 5-340.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini49 – 303255Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini304 – 35855AGC-kinase C-terminalAdd
BLAST

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120454.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP51817.
KOiK04345.
OMAiHRWFRSI.
OrthoDBiEOG7VX8WD.
PhylomeDBiP51817.
TreeFamiTF313399.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

P51817-1 [UniParc]FASTAAdd to Basket

« Hide

        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
Length:358
Mass (Da):40,896
Last modified:October 1, 1996 - v1
Checksum:iB603834E3541CB56
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti43 – 431V → A.
Corresponds to variant rs3752362 [ dbSNP | Ensembl ].
VAR_061744

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85545 mRNA. Translation: CAA59733.1.
BC041073 mRNA. Translation: AAH41073.1.
CCDSiCCDS14125.1.
PIRiI38121.
RefSeqiNP_005035.1. NM_005044.4.
XP_005274617.1. XM_005274560.1.
UniGeneiHs.390788.

Genome annotation databases

EnsembliENST00000262848; ENSP00000262848; ENSG00000183943.
GeneIDi5613.
KEGGihsa:5613.
UCSCiuc010nde.3. human.

Polymorphism databases

DMDMi1709648.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

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.
XP_005274617.1. XM_005274560.1.
UniGenei Hs.390788.

3D structure databases

ProteinModelPortali P51817.
SMRi P51817. Positions 5-340.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111599. 6 interactions.
IntActi P51817. 4 interactions.
STRINGi 9606.ENSP00000262848.

Chemistry

BindingDBi P51817.
ChEMBLi CHEMBL5818.
GuidetoPHARMACOLOGYi 2175.

PTM databases

PhosphoSitei P51817.

Polymorphism databases

DMDMi 1709648.

Proteomic databases

MaxQBi P51817.
PaxDbi P51817.
PRIDEi P51817.

Protocols and materials databases

DNASUi 5613.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262848 ; ENSP00000262848 ; ENSG00000183943 .
GeneIDi 5613.
KEGGi hsa:5613.
UCSCi uc010nde.3. human.

Organism-specific databases

CTDi 5613.
GeneCardsi GC0XM003515.
H-InvDB HIX0202211.
HGNCi HGNC:9441. PRKX.
HPAi HPA015324.
MIMi 300083. gene.
neXtProti NX_P51817.
PharmGKBi PA33786.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00770000120454.
HOGENOMi HOG000233033.
HOVERGENi HBG108317.
InParanoidi P51817.
KOi K04345.
OMAi HRWFRSI.
OrthoDBi EOG7VX8WD.
PhylomeDBi P51817.
TreeFami TF313399.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
SignaLinki P51817.

Miscellaneous databases

GenomeRNAii 5613.
NextBioi 21818.
PROi P51817.
SOURCEi Search...

Gene expression databases

Bgeei P51817.
CleanExi HS_PRKX.
Genevestigatori P51817.

Family and domain databases

InterProi IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS51285. 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPRKX_HUMAN
AccessioniPrimary (citable) accession number: P51817
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 26, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3