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P27791

- KAPCA_RAT

UniProt

P27791 - KAPCA_RAT

Protein

cAMP-dependent protein kinase catalytic subunit alpha

Gene

Prkaca

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca2+, leading to reduced amplitude and increased frequency of store overload-induced Ca2+ release (SOICR) characterized by an increased rate of Ca2+ release and propagation velocity of spontaneous Ca2+ waves, despite reduced wave amplitude and resting cytosolic Ca2+. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation By similarity. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei73 – 731ATPPROSITE-ProRule annotation
    Active sitei167 – 1671Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi50 – 589ATPPROSITE-ProRule annotation
    Nucleotide bindingi122 – 1287ATPPROSITE-ProRule annotation
    Nucleotide bindingi169 – 1724ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cAMP-dependent protein kinase activity Source: RGD
    3. protein binding Source: RGD
    4. protein complex binding Source: RGD
    5. protein kinase A regulatory subunit binding Source: RGD
    6. protein kinase binding Source: BHF-UCL
    7. Rab GTPase binding Source: UniProtKB

    GO - Biological processi

    1. negative regulation of meiotic cell cycle Source: RGD
    2. peptidyl-serine phosphorylation Source: RGD
    3. protein phosphorylation Source: RGD
    4. regulation of cellular respiration Source: RGD
    5. regulation of synaptic transmission, glutamatergic Source: RGD

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, cAMP, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.11. 5301.
    ReactomeiREACT_217998. Gluconeogenesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    cAMP-dependent protein kinase catalytic subunit alpha (EC:2.7.11.11)
    Short name:
    PKA C-alpha
    Gene namesi
    Name:Prkaca
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3389. Prkaca.

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity. Nucleus By similarity. Mitochondrion By similarity
    Note: Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in meiotically incompetent oocytes. Associated to mitochondrion as meiotic competence is acquired. Aggregates around the germinal vesicles (GV) at the immature GV stage oocytes By similarity.By similarity
    Isoform 2 : Cell projectionciliumflagellum By similarity
    Note: Expressed in the midpiece region of the sperm flagellum.By similarity

    GO - Cellular componenti

    1. cAMP-dependent protein kinase complex Source: RGD
    2. cilium Source: UniProtKB-KW
    3. cytoplasm Source: RGD
    4. cytosol Source: Reactome
    5. Golgi apparatus Source: RGD
    6. membrane Source: RGD
    7. mitochondrion Source: UniProtKB-SubCell
    8. neuron projection Source: RGD
    9. nucleoplasm Source: Reactome
    10. nucleus Source: RGD
    11. perinuclear region of cytoplasm Source: RGD
    12. plasma membrane Source: UniProtKB-SubCell
    13. protein complex Source: RGD
    14. sperm midpiece Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cilium, Cytoplasm, Flagellum, Membrane, Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 351350cAMP-dependent protein kinase catalytic subunit alphaPRO_0000086055Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycine1 Publication
    Modified residuei3 – 31Deamidated asparagine; partial1 Publication
    Modified residuei11 – 111Phosphoserine; by autocatalysisBy similarity
    Modified residuei49 – 491PhosphothreonineBy similarity
    Modified residuei140 – 1401Phosphoserine1 Publication
    Modified residuei196 – 1961PhosphothreonineBy similarity
    Modified residuei198 – 1981Phosphothreonine; by PDPK11 Publication
    Modified residuei202 – 2021PhosphothreonineBy similarity
    Modified residuei331 – 3311PhosphotyrosineBy similarity
    Modified residuei339 – 3391PhosphoserineBy similarity

    Post-translational modificationi

    Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.1 Publication
    Autophosphorylated. Phosphorylation is enhanced by vitamin K2. Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity By similarity.By similarity
    Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficienncy.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Phosphoprotein

    Proteomic databases

    PaxDbiP27791.
    PRIDEiP27791.

    PTM databases

    PhosphoSiteiP27791.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. Isoform 2 is round spermatid specific.2 Publications

    Developmental stagei

    In spermatids, isoform 1 is expressed until spermatids become elutriated, whereafter isoform 2 is expressed.1 Publication

    Gene expression databases

    GenevestigatoriP27791.

    Interactioni

    Subunit structurei

    A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes By similarity. Interacts with APOBEC3G and AICDA By similarity. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly.By similarity2 Publications

    Protein-protein interaction databases

    IntActiP27791. 3 interactions.
    MINTiMINT-4564372.

    Structurei

    Secondary structure

    1
    351
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi21 – 3212
    Helixi41 – 433
    Beta strandi44 – 496
    Beta strandi59 – 635
    Turni64 – 663
    Beta strandi69 – 768
    Helixi77 – 826
    Helixi86 – 9712
    Beta strandi107 – 1126
    Beta strandi114 – 1229
    Helixi129 – 1368
    Helixi141 – 16020
    Helixi170 – 1723
    Beta strandi173 – 1753
    Beta strandi181 – 1833
    Helixi203 – 2053
    Helixi208 – 2114
    Helixi219 – 23416
    Helixi244 – 25310
    Helixi264 – 27310
    Turni278 – 2803
    Turni286 – 2894
    Helixi290 – 2934
    Helixi296 – 2983
    Helixi303 – 3086
    Turni345 – 3506

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3TNPX-ray2.30C/F2-351[»]
    3TNQX-ray3.10B2-351[»]
    ProteinModelPortaliP27791.
    SMRiP27791. Positions 13-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini44 – 298255Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini299 – 35153AGC-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.
    PhylomeDBiP27791.

    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]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P27791-1) [UniParc]FASTAAdd to Basket

    Also known as: C-alpha-1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WEDPSQNTAQ LDHFDRIKTL    50
    GTGSFGRVML VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN 100
    FPFLVKLEFS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ 150
    IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY IQVTDFGFAK RVKGRTWTLC 200
    GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK 250
    IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 300
    TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE 350
    F 351
    Length:351
    Mass (Da):40,620
    Last modified:January 23, 2007 - v2
    Checksum:i4763ACD074AB2384
    GO
    Isoform 2 (identifier: P27791-2) [UniParc]FASTAAdd to Basket

    Also known as: Cs

    The sequence of this isoform differs from the canonical sequence as follows:
         2-15: GNAAAAKKGSEQES → MASNSND

    Show »
    Length:344
    Mass (Da):40,010
    Checksum:i2FCD274075C7C08B
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 1514GNAAA…SEQES → MASNSND in isoform 2. 1 PublicationVSP_013277Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57986 mRNA. Translation: CAA41052.1.
    AY375243 mRNA. Translation: AAQ81631.1.
    PIRiS16240. OKRT2C.
    UniGeneiRn.20.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57986 mRNA. Translation: CAA41052.1 .
    AY375243 mRNA. Translation: AAQ81631.1 .
    PIRi S16240. OKRT2C.
    UniGenei Rn.20.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3TNP X-ray 2.30 C/F 2-351 [» ]
    3TNQ X-ray 3.10 B 2-351 [» ]
    ProteinModelPortali P27791.
    SMRi P27791. Positions 13-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P27791. 3 interactions.
    MINTi MINT-4564372.

    Chemistry

    BindingDBi P27791.
    ChEMBLi CHEMBL3390.

    PTM databases

    PhosphoSitei P27791.

    Proteomic databases

    PaxDbi P27791.
    PRIDEi P27791.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    RGDi 3389. Prkaca.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    PhylomeDBi P27791.

    Enzyme and pathway databases

    BRENDAi 2.7.11.11. 5301.
    Reactomei REACT_217998. Gluconeogenesis.

    Gene expression databases

    Genevestigatori P27791.

    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. "Rat C alpha catalytic subunit of the cAMP-dependent protein kinase: cDNA sequence and evidence that it is the only isoform expressed in myoblasts."
      Wiemann S., Voss H., Kinzel V., Pyerin W.
      Biochim. Biophys. Acta 1089:254-256(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    2. "A conserved deamidation site at Asn 2 in the catalytic subunit of mammalian cAMP-dependent protein kinase detected by capillary LC-MS and tandem mass spectrometry."
      Jedrzejewski P.T., Girod A., Tholey A., Koenig N., Thullner S., Kinzel V., Bossemeyer D.
      Protein Sci. 7:457-469(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-8 (ISOFORM 1), MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
    3. "Phosphorylation of rat spermatidal protein TP2 by sperm-specific protein kinase A and modulation of its transport into the haploid nucleus."
      Ullas K.S., Rao M.R.S.
      J. Biol. Chem. 278:52673-52680(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-313 (ISOFORM 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Strain: Wistar.
    4. "Protein kinase A in the pedunculopontine tegmental nucleus of rat contributes to regulation of rapid eye movement sleep."
      Datta S., Desarnaud F.
      J. Neurosci. 30:12263-12273(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN RAPID EYE MOVEMENT SLEEP.
    5. "RAB13 regulates Sertoli cell permeability barrier dynamics through protein kinase A."
      Su W., Liu X.
      J. Mol. Endocrinol. 50:305-318(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RAB13.
    6. "Structure and allostery of the PKA RIIbeta tetrameric holoenzyme."
      Zhang P., Smith-Nguyen E.V., Keshwani M.M., Deal M.S., Kornev A.P., Taylor S.S.
      Science 335:712-716(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-351 IN COMPLEX WITH MOUSE PRKAR2B, SUBUNIT, PHOSPHORYLATION AT SER-140 AND THR-198.

    Entry informationi

    Entry nameiKAPCA_RAT
    AccessioniPrimary (citable) accession number: P27791
    Secondary accession number(s): Q6UA68
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 140 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3