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P27791

- KAPCA_RAT

UniProt

P27791 - KAPCA_RAT

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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

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 complex binding Source: RGD
  4. protein kinase A regulatory subunit binding Source: RGD
  5. protein kinase binding Source: BHF-UCL
  6. 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
Complete GO annotation...

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. cytoplasm Source: RGD
  3. cytosol Source: Reactome
  4. Golgi apparatus Source: RGD
  5. membrane Source: RGD
  6. mitochondrion Source: UniProtKB-KW
  7. motile cilium Source: UniProtKB-KW
  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-KW
  13. protein complex Source: RGD
  14. sperm midpiece Source: UniProtKB
Complete GO annotation...

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.
InParanoidiP27791.
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.
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

        10         20         30         40         50
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WEDPSQNTAQ LDHFDRIKTL
60 70 80 90 100
GTGSFGRVML VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN
110 120 130 140 150
FPFLVKLEFS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ
160 170 180 190 200
IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY IQVTDFGFAK RVKGRTWTLC
210 220 230 240 250
GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK
260 270 280 290 300
IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT
310 320 330 340 350
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE

F
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.
InParanoidi P27791.
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.
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 29, 2014
This is version 141 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