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P51817

- PRKX_HUMAN

UniProt

P51817 - PRKX_HUMAN

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
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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
    3. protein binding 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

    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

    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. 5 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.
    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_dom.
    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

    MEAPGLAQAA AAESDSRKVA EETPDGAPAL CPSPEALSPE PPVYSLQDFD    50
    TLATVGTGTF GRVHLVKEKT AKHFFALKVM SIPDVIRLKQ EQHVHNEKSV 100
    LKEVSHPFLI RLFWTWHDER FLYMLMEYVP GGELFSYLRN RGRFSSTTGL 150
    FYSAEIICAI EYLHSKEIVY RDLKPENILL DRDGHIKLTD FGFAKKLVDR 200
    TWTLCGTPEY LAPEVIQSKG HGRAVDWWAL GILIFEMLSG FPPFFDDNPF 250
    GIYQKILAGK IDFPRHLDFH VKDLIKKLLV VDRTRRLGNM KNGANDVKHH 300
    RWFRSVDWEA VPQRKLKPPI VPKIAGDGDT SNFETYPEND WDTAAPVPQK 350
    DLEIFKNF 358
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. 5 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.
    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_dom.
    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

    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: October 1, 2014
    This is version 134 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