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P36887

- KAPCA_PIG

UniProt

P36887 - KAPCA_PIG

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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

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
Complete GO annotation...

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-KW
  2. nucleus Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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.
InParanoidiP36887.

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.

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

P36887-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL
60 70 80 90 100
GTGSFGRVML VKHKETGNHF AMKILDKQKV VKLKQIEHTL NEKRILQAVN
110 120 130 140 150
FPFLVKLEYS 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 NEKCGKEFSE

F
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.
InParanoidi P36887.

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.
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 29, 2014
This is version 121 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