Q8MJ44 (KAPCA_CANFA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
cAMP-dependent protein kinase catalytic subunit alpha
Short name=PKA C-alpha
EC=2.7.11.11

Gene names

Name:

PRKACA

Organism

Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › Canis lupus

Protein attributes

Sequence length	350 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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, TRPC1 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+. TRPC1 activation by phosphorylation promotes Ca2+ influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (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. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. 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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Cell membrane 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.
Tissue specificity	Ubiquitously expressed in mammalian tissues.
Post-translational modification	Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively By similarity. Autophosphorylated. Phosphorylation is enhanced by vitamin K2. Phosphorylated on threonine and serine residues. Phosphorylation on Thr-197 is required for full activity By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Mitochondrion Nucleus
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-dependent protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 350	349	cAMP-dependent protein kinase catalytic subunit alpha		PRO_0000086050
Regions
	Domain	43 – 297	255	Protein kinase
	Domain	298 – 350	53	AGC-kinase C-terminal
	Nucleotide binding	49 – 57	9	ATP By similarity
	Nucleotide binding	121 – 127	7	ATP By similarity
	Nucleotide binding	168 – 171	4	ATP By similarity
Sites
	Active site	166	1	Proton acceptor By similarity
	Binding site	72	1	ATP By similarity
Amino acid modifications
	Modified residue	3	1	Deamidated asparagine By similarity
	Modified residue	10	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	48	1	Phosphothreonine By similarity
	Modified residue	139	1	Phosphoserine By similarity
	Modified residue	195	1	Phosphothreonine By similarity
	Modified residue	197	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	201	1	Phosphothreonine By similarity
	Modified residue	338	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q8MJ44 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: DC827D8A06358E8F	FASTA	350	40,546
	10 20 30 40 50 60 MGNAAAKKGS EQESVKEFLA KAKEDFLKKW ENPAQNTAHL DQFERIKTLG TGSFGRVMLV 70 80 90 100 110 120 KHKETGNHFA MKILDKQKVV KLKQIEHTLN EKRILQAVNF PFLVKLEFSF KDNSNLYMVM 130 140 150 160 170 180 EYVPGGEMFS HLRRIGRFSE PHARFYAAQI VLTFEYLHSL DLIYRDLKPE NLLIDQQGYI 190 200 210 220 230 240 QVTDFGFAKR VKGRTWTLCG TPEYLAPEII LSKGYNKAVD WWALGVLIYE MAAGYPPFFA 250 260 270 280 290 300 DQPIQIYEKI VSGKVRFPSH FSSDLKDLLR NLLQVDLTKR FGNLKNGVND IKNHKWFATT 310 320 330 340 350 DWIAIYQRKV EAPFIPKFKG PGDTSNFDDY EEEEIRVSIN EKCGKEFCEF

References

[1]	"Cloning and sequencing of protein kinase A alpha from dog heart." Mishra S., Rastogi S., Tiwari N., Sabbah H.N., Gupta R.C. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF525132 mRNA. Translation: AAM88381.1.
RefSeq	NP_001003032.1. NM_001003032.1.
UniGene	Cfa.74.
3D structure databases
ProteinModelPortal	Q8MJ44.
SMR	Q8MJ44. Positions 4-350.
ModBase	Search...
Protein-protein interaction databases
STRING	9615.ENSCAFP00000024262.
Proteomic databases
PRIDE	Q8MJ44.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	403556.
KEGG	cfa:403556.
Organism-specific databases
CTD	5566.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233033.
HOVERGEN	HBG108317.
InParanoid	Q8MJ44.
KO	K04345.
OrthoDB	EOG4RXZ0C.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
NextBio	20817065.

Entry information

Entry name

KAPCA_CANFA

Accession

Primary (citable) accession number: Q8MJ44

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program