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P36887

- KAPCA_PIG

UniProt

P36887 - KAPCA_PIG

Protein

cAMP-dependent protein kinase catalytic subunit alpha

Gene

PRKACA

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 4 (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. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) By similarity. Phosphorylates APOBEC3G and AICDA 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 – 731ATP
    Active sitei167 – 1671Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi50 – 589ATP
    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: UniProtKB-EC

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, cAMP, Nucleotide-binding

    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
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Unplaced

    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

    GO - Cellular componenti

    1. mitochondrion Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 351350cAMP-dependent protein kinase catalytic subunit alphaPRO_0000086054Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycine1 Publication
    Modified residuei3 – 31Deamidated asparagine; partial2 Publications
    Modified residuei11 – 111Phosphoserine; by autocatalysisBy similarity
    Modified residuei49 – 491PhosphothreonineBy similarity
    Modified residuei140 – 1401PhosphoserineBy similarity
    Modified residuei196 – 1961PhosphothreonineBy similarity
    Modified residuei198 – 1981Phosphothreonine; by PDPK1By similarity
    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.2 Publications
    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

    PaxDbiP36887.
    PRIDEiP36887.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed in mammalian tissues.

    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. Activates 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 similarity.By similarity

    Protein-protein interaction databases

    IntActiP36887. 1 interaction.

    Structurei

    Secondary structure

    1
    351
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 63
    Helixi11 – 3222
    Helixi41 – 433
    Beta strandi44 – 529
    Beta strandi57 – 637
    Turni64 – 663
    Beta strandi69 – 768
    Helixi77 – 826
    Helixi86 – 9813
    Beta strandi107 – 1126
    Beta strandi114 – 1218
    Helixi129 – 1368
    Helixi141 – 16020
    Helixi170 – 1723
    Beta strandi173 – 1753
    Beta strandi181 – 1833
    Helixi203 – 2053
    Helixi208 – 2114
    Helixi220 – 23415
    Helixi244 – 25310
    Helixi264 – 27310
    Turni278 – 2803
    Turni282 – 2843
    Turni286 – 2894
    Helixi290 – 2934
    Helixi296 – 2983
    Helixi303 – 3075
    Turni322 – 3287
    Helixi346 – 3483

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CDKX-ray2.00A/B2-351[»]
    1CMKX-ray2.90E2-351[»]
    1CTPX-ray2.90E2-351[»]
    ProteinModelPortaliP36887.
    SMRiP36887. Positions 2-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP36887.

    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.

    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.

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

    P36887-1 [UniParc]FASTAAdd to Basket

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    MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL    50
    GTGSFGRVML VKHKETGNHF AMKILDKQKV VKLKQIEHTL NEKRILQAVN 100
    FPFLVKLEYS 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 NEKCGKEFSE 350
    F 351
    Length:351
    Mass (Da):40,617
    Last modified:January 23, 2007 - v4
    Checksum:iB65EC7C42DD56DE5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X07617 mRNA. Translation: CAA30470.1.
    PIRiS00086.
    UniGeneiSsc.13872.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X07617 mRNA. Translation: CAA30470.1 .
    PIRi S00086.
    UniGenei Ssc.13872.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CDK X-ray 2.00 A/B 2-351 [» ]
    1CMK X-ray 2.90 E 2-351 [» ]
    1CTP X-ray 2.90 E 2-351 [» ]
    ProteinModelPortali P36887.
    SMRi P36887. Positions 2-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P36887. 1 interaction.

    Proteomic databases

    PaxDbi P36887.
    PRIDEi P36887.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.

    Miscellaneous databases

    EvolutionaryTracei P36887.

    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. "Multiple mRNA species code for the catalytic subunit of the cAMP-dependent protein kinase from LLC-PK1 cells. Evidence for two forms of the catalytic subunit."
      Adavani S.R., Schwarz M., Showers M.O., Maurer R.A., Hemmings B.A.
      Eur. J. Biochem. 167:221-226(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 195-351.
    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, MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
    3. "Intracellular distribution of mammalian protein kinase A catalytic subunit altered by conserved Asn2 deamidation."
      Pepperkok R., Hotz-Wagenblatt A., Koenig N., Girod A., Bossemeyer D., Kinzel V.
      J. Cell Biol. 148:715-726(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEAMIDATION AT ASN-3, SUBCELLULAR LOCATION.
    4. "Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor."
      Zheng J., Knighton D.R., ten Eyck L.F., Karlsson R., Xuong N.-H., Taylor S.S., Sowadski J.M.
      Biochemistry 32:2154-2161(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH PKIA.

    Entry informationi

    Entry nameiKAPCA_PIG
    AccessioniPrimary (citable) accession number: P36887
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 120 of the entry and version 4 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