Reviewed, UniProtKB/Swiss-Prot P27791 (KAPCA_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by cAMP.
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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Translocates into the nucleus (monomeric catalytic subunit) By similarity. The inactive holoenzyme is found in the cytoplasm By similarity.
Tissue specificity	Ubiquitously expressed. Isoform 2 is round spermatid specific. Ref.1 Ref.3
Developmental stage	In spermatids, isoform 1 is expressed until spermatids become elutriated, whereafter isoform 2 is expressed. Ref.3
Post-translational modification	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.
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	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of meiotic cell cycle Inferred from direct assay. Source: RGD peptidyl-serine phosphorylation Inferred from direct assay. Source: RGD regulation of cellular respiration Inferred from direct assay. Source: RGD regulation of synaptic transmission, glutamatergic Inferred from direct assay. Source: RGD
Cellular component	Golgi apparatus Inferred from direct assay. Source: RGD cAMP-dependent protein kinase complex Inferred from direct assay. Source: RGD cytosol Inferred from Experiment. Source: Reactome membrane fraction Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD perinuclear region of cytoplasm Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-dependent protein kinase activity Inferred from direct assay. Source: RGD protein complex binding Inferred from physical interaction. Source: RGD protein kinase A regulatory subunit binding Inferred by curator. Source: RGD protein kinase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P27791-1)

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.

Isoform 2 (identifier: P27791-2)

Also known as: Cs;

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MGNAAAAKKGSEQES → MASNSND

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 351	350	cAMP-dependent protein kinase catalytic subunit alpha		PRO_0000086055
Regions
	Domain	44 – 298	255	Protein kinase
	Domain	299 – 351	53	AGC-kinase C-terminal
	Nucleotide binding	50 – 58	9	ATP By similarity
Sites
	Active site	167	1	Proton acceptor By similarity
	Binding site	73	1	ATP By similarity
Amino acid modifications
	Modified residue	3	1	Deamidated asparagine; partial
	Modified residue	11	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	35	1	Phosphoserine By similarity
	Modified residue	49	1	Phosphothreonine By similarity
	Modified residue	140	1	Phosphoserine By similarity
	Modified residue	196	1	Phosphothreonine By similarity
	Modified residue	198	1	Phosphothreonine By similarity
	Modified residue	202	1	Phosphothreonine By similarity
	Modified residue	339	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine
Natural variations
	Alternative sequence	1 – 15	15	MGNAA…SEQES → MASNSND in isoform 2.		VSP_013277

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (C-alpha-1) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 4763ACD074AB2384	FASTA	351	40,620
	10 20 30 40 50 60 MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WEDPSQNTAQ LDHFDRIKTL GTGSFGRVML 70 80 90 100 110 120 VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 130 140 150 160 170 180 MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 190 200 210 220 230 240 IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 250 260 270 280 290 300 ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 310 320 330 340 350 TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE F
	Isoform 2 (Cs). Checksum: A41B65C8AB162401	FASTA	343	39,879
	10 20 30 40 50 60 MASNSNDVKE FLAKAKEDFL KKWEDPSQNT AQLDHFDRIK TLGTGSFGRV MLVKHKESGN 70 80 90 100 110 120 HYAMKILDKQ KVVKLKQIEH TLNEKRILQA VNFPFLVKLE FSFKDNSNLY MVMEYVPGGE 130 140 150 160 170 180 MFSHLRRIGR FSEPHARFYA AQIVLTFEYL HSLDLIYRDL KPENLLIDQQ GYIQVTDFGF 190 200 210 220 230 240 AKRVKGRTWT LCGTPEYLAP EIILSKGYNK AVDWWALGVL IYEMAAGYPP FFADQPIQIY 250 260 270 280 290 300 EKIVSGKVRF PSHFSSDLKD LLRNLLQVDL TKRFGNLKNG VNDIKNHKWF ATTDWIAIYQ 310 320 330 340 RKVEAPFIPK FKGPGDTSNF DDYEEEEIRV SINEKCGKEF TEF

References

[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: 1711374] [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: 9521123] [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: 14514679] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-313 (ISOFORM 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: Wistar.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X57986 mRNA. Translation: CAA41052.1. AY375243 mRNA. Translation: AAQ81631.1.
IPI	IPI00200013. IPI00555215.
PIR	OKRT2C. S16240.
UniGene	Rn.20
3D structure databases
HSSP	HSSP built from PDB template 1CTP based on UniProtKB P36887.
SMR	P27791. Positions 10-351.
ModBase	Search...
Protein-protein interaction databases
STRING	P27791.
PTM databases
PhosphoSite	P27791.
Proteomic databases
PRIDE	P27791.
Genome annotation databases
Ensembl	ENSRNOT00000007281; ENSRNOP00000007281; ENSRNOG00000005257; Rattus norvegicus. [Genome view] ENSRNOT00000007303; ENSRNOP00000007303; ENSRNOG00000005257; Rattus norvegicus. [Genome view] ENSRNOT00000041717; ENSRNOP00000044732; ENSRNOG00000005257; Rattus norvegicus. [Genome view]
Organism-specific databases
RGD	3389. Prkaca.
Phylogenomic databases
HOVERGEN	P27791.
Enzyme and pathway databases
BRENDA	2.7.11.11. 248.
Gene expression databases
ArrayExpress	P27791.
Genevestigator	P27791.
GermOnline	ENSRNOG00000005257. Rattus norvegicus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
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 Resources
BindingDB	P27791.

Entry information

Entry name

KAPCA_RAT

Accession

Primary (citable) accession number: P27791
Secondary accession number(s): Q6UA68

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)